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Xie Y, An L, Wang X, Ma Y, Bayoude A, Fan X, Yu B, Li R. Protection effect of Dioscoreae Rhizoma against ethanol-induced gastric injury in vitro and in vivo: A phytochemical and pharmacological study. JOURNAL OF ETHNOPHARMACOLOGY 2024; 333:118427. [PMID: 38844251 DOI: 10.1016/j.jep.2024.118427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 05/31/2024] [Accepted: 06/03/2024] [Indexed: 06/13/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Dioscoreae Rhizoma, a kind of Chinese yam, is a medicinal and edible plant used in China for strengthening the spleen and stomach. However, there is a lack of modern pharmacology studies regarding its anti-gastric injury activity. AIM OF THE STUDY This study aimed to investigate the phytochemical composition of Chinese yam aqueous extract (CYW) and evaluate its gastroprotective effects against ethanol-induced gastric injury in vitro and in vivo. MATERIALS AND METHODS The active components of CYW were identified using HPLC-QTOF-MS/MS in combination with the GNPS molecular networking and network pharmacology. In vitro studies were performed in the RAW264.7/GES-1 cell coculture system. In vivo study, mice were treated with CYW (0.31, 0.63, and 3.14 g/kg BW, orally) for 14 days, followed by a single oral dose of ethanol (10 mL/kg BW) to induce gastric injury. The biochemical, inflammation and oxidative stress markers were analyzed using commercial kits. Histopathology was used to assess the degree of gastric injury. Gene and protein expressions were studied using RT-qPCR and western blotting, respectively. RESULTS CYW significantly restored the levels of SOD, GPx and CAT, and reduced the MDA content. Further analyses showed that CYW significantly alleviated the gastric oxidative stress by inhibiting the inflammation via decreasing p-NF-κB and p-IκB-α expression levels and inhibiting the generation of IL-6, TNF-α, and IL-1β. At the same time, the fraction remarkably upregulated Bcl-2, downregulated Bax and increased growth factor secretion, thereby prevented gastric mucous cell. Besides, The combination of HPLC-QTOF-MS/MS, GNPS molecular networking analysis, and network pharmacology demonstrated that linoleic acid, 3-acetyl-11-keto-beta-boswellic acid, adenosine, aminocaproic acid, tyramine, DL-tryptophan, cycloleucine, lactulose, melibiose, alpha-beta-trehalose, and sucrose would be the main active compounds of CYW against ethanol-induced gastric injury. CONCLUSION This study showed that CYW is potentially rich source of anti-oxidant and anti-inflammatory bioactive compounds. It showed efficacy against ethanol-induced gastric injury by inhibiting inflammation, oxidative stress, and apoptosis in the stomach. The results of the current work indicate that Dioscoreae Rhizoma could be utilized as a type of natural resource for production of new medicine and functional foods to prevent and/or ameliorate ethanol-induced gastric injury.
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Affiliation(s)
- Yujun Xie
- Jiangsu Provincial Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
| | - Luyao An
- Jiangsu Provincial Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
| | - Xiaoyan Wang
- Jiangsu Provincial Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
| | - Yajie Ma
- Jiangsu Provincial Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
| | - Alamusi Bayoude
- Jiangsu Provincial Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
| | - Xinxin Fan
- Jiangsu Provincial Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
| | - Boyang Yu
- Jiangsu Provincial Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
| | - Renshi Li
- Jiangsu Provincial Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
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Hsu CY, Mustafa MA, Moath Omar T, Taher SG, Ubaid M, Gilmanova NS, Nasrat Abdulraheem M, Saadh MJ, Athab AH, Mirzaei R, Karampoor S. Gut instinct: harnessing the power of probiotics to tame pathogenic signaling pathways in ulcerative colitis. Front Med (Lausanne) 2024; 11:1396789. [PMID: 39323474 PMCID: PMC11422783 DOI: 10.3389/fmed.2024.1396789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 08/22/2024] [Indexed: 09/27/2024] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) marked by persistent inflammation of the mucosal lining of the large intestine, leading to debilitating symptoms and reduced quality of life. Emerging evidence suggests that an imbalance of the gut microbiota plays a crucial role in UC pathogenesis, and various signaling pathways are implicated in the dysregulated immune response. Probiotics are live microorganisms that confer health benefits to the host, have attracted significant attention for their potential to restore gut microbial balance and ameliorate inflammation in UC. Recent studies have elucidated the mechanisms by which probiotics modulate these signaling pathways, often by producing anti-inflammatory molecules and promoting regulatory immune cell function. For example, probiotics can inhibit the nuclear factor-κB (NF-κB) pathway by stabilizing Inhibitor of kappa B alpha (IκBα), dampening the production of proinflammatory cytokines. Similarly, probiotics can modulate the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, suppressing the activation of STAT1 and STAT3 and thus reducing the inflammatory response. A better understanding of the underlying mechanisms of probiotics in modulating pathogenic signaling pathways in UC will pave the way for developing more effective probiotic-based therapies. In this review, we explore the mechanistic role of probiotics in the attenuation of pathogenic signaling pathways, including NF-κB, JAK/STAT, mitogen-activated protein kinases (MAPKs), Wnt/β-catenin, the nucleotide-binding domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) inflammasome, Toll-like receptors (TLRs), interleukin-23 (IL-23)/IL-17 signaling pathway in UC.
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Affiliation(s)
- Chou-Yi Hsu
- Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
- Thunderbird School of Global Management, Arizona State University Tempe Campus, Phoenix, AZ, United States
| | - Mohammed Ahmed Mustafa
- Department of Medical Laboratory Technology, Imam Jaafar AL-Sadiq University, Baghdad, Iraq
- Department of Pathological Analyzes, College of Applied Sciences, University of Samarra, Samarra, Iraq
| | - Thabit Moath Omar
- Department of Medical Laboratory Technics, College of Health and Medical Technology, Alnoor University, Mosul, Iraq
| | - Sada Gh Taher
- Department of Pharmacy, National University of Science and Technology, Dhi Qar, Iraq
| | - Mohammed Ubaid
- Department of MTL, Medical Technical College, Al-Farahidi University, Baghdad, Iraq
| | - Nataliya S. Gilmanova
- Department of Prosthetic Dentistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | | | | | - Aya H. Athab
- Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq
| | - Rasoul Mirzaei
- Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Sajad Karampoor
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran
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Sumneang N, Pintha K, Kongkarnka S, Suttajit M, Kangwan N. Protective Effect of Perilla Seed Meal and Perilla Seed Extract against Dextran Sulfate Sodium-Induced Ulcerative Colitis through Suppressing Inflammatory Cytokines in Mice. Molecules 2024; 29:1940. [PMID: 38731431 PMCID: PMC11085631 DOI: 10.3390/molecules29091940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 04/19/2024] [Accepted: 04/23/2024] [Indexed: 05/13/2024] Open
Abstract
An excessive inflammatory response of the gastrointestinal tract is recognized as one of the major contributors to ulcerative colitis (UC). Despite this, effective preventive approaches for UC remain limited. Rosmarinic acid (RA), an enriched fraction from Perilla frutescens, has been shown to exert beneficial effects on disease-related inflammatory disorders. However, RA-enriched perilla seed meal (RAPSM) and perilla seed (RAPS) extracts have not been investigated in dextran sulfate sodium (DSS)-induced UC in mice. RAPSM and RAPS were extracted using the solvent-partitioning method and analyzed with high-pressure liquid chromatography (HPLC). Mice with UC induced using 2.5% DSS for 7 days were pretreated with RAPSM and RAPS (50, 250, 500 mg/kg). Then, the clinical manifestation, colonic histopathology, and serum proinflammatory cytokines were determined. Indeed, DSS-induced UC mice exhibited colonic pathological defects including an impaired colon structure, colon length shortening, and increased serum proinflammatory cytokines. However, RAPSM and RAPS had a protective effect at all doses by attenuating colonic pathology in DSS-induced UC mice, potentially through the suppression of proinflammatory cytokines. Concentrations of 50 mg/kg of RAPSM and RAPS were sufficient to achieve a beneficial effect in UC mice. This suggests that RAPSM and RAPS have a preventive effect against DSS-induced UC, potentially through alleviating inflammatory responses and relieving severe inflammation in the colon.
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Affiliation(s)
- Natticha Sumneang
- Department of Medical Science, School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand;
- Research Center in Tropical Pathobiology, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | - Komsak Pintha
- Division of Biochemistry, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand; (K.P.); (M.S.)
| | - Sarawut Kongkarnka
- Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand;
| | - Maitree Suttajit
- Division of Biochemistry, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand; (K.P.); (M.S.)
| | - Napapan Kangwan
- Division of Physiology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand
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Rezaei Z, Momtaz S, Gharazi P, Rahimifard M, Baeeri M, Abdollahi AR, Abdollahi M, Niknejad A, Khayatan D, Farzaei MH, Abdolghaffari AH. Cinnamic Acid Ameliorates Acetic Acid-induced Inflammatory Response through Inhibition of TLR-4 in Colitis Rat Model. Antiinflamm Antiallergy Agents Med Chem 2024; 23:21-30. [PMID: 38361356 DOI: 10.2174/0118715230278980231212103709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 11/16/2023] [Accepted: 11/21/2023] [Indexed: 02/17/2024]
Abstract
BACKGROUND Cinnamic acid, an active compound in cinnamon spp., has anti-inflammatory and antioxidant characteristics and is favorable in managing inflammatory bowel diseases. OBJECTIVES Evaluate cinnamic acid's effects on colitis in rats. METHODS To induce colitis in experimental rats, excluding the sham group, a 4% intrarectal solution of acetic acid was administered. The rats were then given oral doses of cinnamic acid at 30, 45, and 90 mg/kg for two days. The animals were assessed for macroscopic and microscopic changes, and the levels of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) were measured using Eliza kits. Additionally, real-time PCR was performed to examine the gene level of toll-like receptor 4 (TLR-4) in the colon. RESULTS Effective reduction of inflammation in acetic acid-induced colitis was achieved through Cinnamic acid administration at doses of 45 and 90 mg/kg. The decrease was achieved by inhibiting the activities of TNF-α, IL-6, and MPO while downregulating the expression of TLR-4. It is important to note that macroscopic and microscopic evaluations were significant in determining the effectiveness of cinnamic acid in reducing inflammation. CONCLUSION Downregulation of inflammatory cytokines and TLR-4 expression may contribute to cinnamic acid's anti-inflammatory effect.
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Affiliation(s)
- Zahra Rezaei
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Saeideh Momtaz
- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, And Toxicology & Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences, Tehran, 1417614411, Iran
- Gastrointestinal Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Pardis Gharazi
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mahban Rahimifard
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, And Toxicology & Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences, Tehran, 1417614411, Iran
| | - Maryam Baeeri
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, And Toxicology & Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences, Tehran, 1417614411, Iran
| | - Ali Reza Abdollahi
- Department of Pathology, Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Abdollahi
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, And Toxicology & Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences, Tehran, 1417614411, Iran
| | - Amirhossein Niknejad
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Gastrointestinal Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Danial Khayatan
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Gastrointestinal Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Amir Hossein Abdolghaffari
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Gastrointestinal Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
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Guazelli CFS, Fattori V, Colombo BB, Ludwig IS, Vicente LG, Martinez RM, Georgetti SR, Urbano A, Casagrande R, Baracat MM, Verri WA. Development of trans-Chalcone loaded pectin/casein biodegradable microcapsules: Efficacy improvement in the management of experimental colitis. Int J Pharm 2023; 642:123206. [PMID: 37419432 DOI: 10.1016/j.ijpharm.2023.123206] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 07/02/2023] [Accepted: 07/04/2023] [Indexed: 07/09/2023]
Abstract
Improved therapies for inflammatory bowel diseases are sorely needed. Novel therapeutic agents and the development of controlled release systems for targeted tissue delivery are interesting approaches to overcome these barriers. We investigated the activity of trans-chalcone (T) in acetic acid-induced colitis in mice and developed, characterized, and determined the therapeutic effect of pectin/casein polymer microcapsules containing T (MT) in a colitis mouse model. In vitro, compound release was achieved in simulated intestinal fluid but not in the simulated gastric fluid. In vivo, since T at the dose of 3 mg/kg but not 0.3 mg/kg ameliorated colitis, we next tested the effects of MT at 0.3 mg/kg (non-effective dose). MT, but not free T at 0.3 mg/kg, significantly improved colitis outcomes such as neutrophil recruitment, antioxidant capacity, cytokine production, and NF-kB activation. This translated into reduced macro and microscopic damage in the colon. T release from the microcapsules is mediated by a pH-dependent and pectinase-regulated mechanism that provide controlled and prolonged release of T. Moreover, MT lowered the required dose for T therapeutic effect, indicating that could be a suitable pharmaceutical approach to colitis treatment. This is the first demonstration that T or MT is effective at reducing the signs of colitis.
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Affiliation(s)
- Carla F S Guazelli
- Departamento de Ciências Patológicas, Universidade Estadual de Londrina-UEL, Rod. Celso Garcia Cid, Km 380, PR445, 86057-970, Londrina, Paraná, Brazil
| | - Victor Fattori
- Departamento de Ciências Patológicas, Universidade Estadual de Londrina-UEL, Rod. Celso Garcia Cid, Km 380, PR445, 86057-970, Londrina, Paraná, Brazil
| | - Barbara B Colombo
- Departamento de Ciências Patológicas, Universidade Estadual de Londrina-UEL, Rod. Celso Garcia Cid, Km 380, PR445, 86057-970, Londrina, Paraná, Brazil
| | - Isabela S Ludwig
- Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina-UEL, Avenida Robert Koch, 60, Hospital Universitário, 86038-350, Londrina, Paraná, Brazil
| | - Laisa G Vicente
- Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina-UEL, Avenida Robert Koch, 60, Hospital Universitário, 86038-350, Londrina, Paraná, Brazil
| | - Renata M Martinez
- Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina-UEL, Avenida Robert Koch, 60, Hospital Universitário, 86038-350, Londrina, Paraná, Brazil
| | - Sandra R Georgetti
- Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina-UEL, Avenida Robert Koch, 60, Hospital Universitário, 86038-350, Londrina, Paraná, Brazil
| | - Alexandre Urbano
- Departamento de Física, Universidade Estadual de Londrina-UEL, Rod. Celso Garcia Cid, Km 380, PR445, 86057-970, Londrina, Paraná, Brazil
| | - Rubia Casagrande
- Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina-UEL, Avenida Robert Koch, 60, Hospital Universitário, 86038-350, Londrina, Paraná, Brazil
| | - Marcela M Baracat
- Departamento de Ciências Farmacêuticas, Universidade Estadual de Londrina-UEL, Avenida Robert Koch, 60, Hospital Universitário, 86038-350, Londrina, Paraná, Brazil.
| | - Waldiceu A Verri
- Departamento de Ciências Patológicas, Universidade Estadual de Londrina-UEL, Rod. Celso Garcia Cid, Km 380, PR445, 86057-970, Londrina, Paraná, Brazil.
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Huo J, Pei W, Liu G, Sun W, Wu J, Huang M, Lu W, Sun J, Sun B. Huangshui Polysaccharide Exerts Intestinal Barrier Protective Effects through the TLR4/MyD88/NF- κB and MAPK Signaling Pathways in Caco-2 Cells. Foods 2023; 12:foods12030450. [PMID: 36765977 PMCID: PMC9914309 DOI: 10.3390/foods12030450] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/09/2023] [Accepted: 01/14/2023] [Indexed: 01/20/2023] Open
Abstract
Several reports have demonstrated that natural polysaccharides exert protective effects on intestinal barrier function. In our previous study, we isolated a polysaccharide named HSP-W from Huangshui (HS). In the present study, the protective role of HSP-W in LPS-induced intestinal barrier dysfunction was determined by several molecular biological techniques. The results showed that HSP-W treatment alleviated the deduced TEER and increased the permeability of intestinal epithelial cells induced by LPS through inhibiting the release of inflammatory cytokines and enhancing the expression of tight junction (TJ) proteins. The underlying molecular mechanisms were elucidated by RNA-seq technique, which indicated that the differentially expressed genes (DEGs) between the LPS-treated and LPS+HSP-W-treated groups were enriched in the "MAPK" signaling pathway. Notably, the overlapping DEGs reversed by HSP-W intervention highlighted the pathways of the "Toll-like receptor" and "NF-κB" signaling pathways. The suppression of p38 and NF-κB were mediated by the inhibition of MyD88. Furthermore, HSP-W treatment prevented the translocation of NF-κB to nucleus, thus inhibiting the release of TNF-α, IL-6, and IL-1β. Overall, HSP-W has beneficial effects on LPS-induced inflammation; it protects the intestinal barrier from injury in Caco-2 cells through inhibiting the TLR4/MyD88/NF-κB and p38 MAPK signaling pathways.
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Affiliation(s)
- Jiaying Huo
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
| | - Wenhao Pei
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China
| | - Guoying Liu
- Anhui Gujing Distillery Co. Ltd., Bozhou 236820, China
| | - Weizheng Sun
- School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
| | - Jihong Wu
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China
- Correspondence: ; Tel.: +86-156-5271-2036
| | - Mingquan Huang
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China
| | - Wei Lu
- Anhui Gujing Distillery Co. Ltd., Bozhou 236820, China
| | - Jinyuan Sun
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China
| | - Baoguo Sun
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China
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Wang YJ, Li QM, Zha XQ, Luo JP. Intervention and potential mechanism of non-starch polysaccharides from natural resources on ulcerative colitis: A review. Int J Biol Macromol 2022; 210:545-564. [PMID: 35513106 DOI: 10.1016/j.ijbiomac.2022.04.208] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 04/08/2022] [Accepted: 04/27/2022] [Indexed: 12/12/2022]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology that affects the colon and rectum. It has evolved into a global burden due to the high incidence in developed countries and the highly-increased incidence in developing countries. Non-starch polysaccharides (NSPs) from natural resources, as a type of functional carbohydrates, have a significant therapeutic effect on UC because of their good anti-inflammatory and immunomodulatory activities. Based on the etiology and pathogenesis of UC, this review summarizes the intervention effects and mechanisms of NSPs in the prevention and treatment of UC. The results showed that NSPs can improve UC by protecting the intestinal mucosal barrier, regulating the immune response of the intestinal mucosa, and remodeling the intestinal flora and metabolites. These contents provide theoretical basis for the application of polysaccharides in the prevention and treatment of UC.
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Affiliation(s)
- Yu-Jing Wang
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China; Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, Hefei 230601, China
| | - Qiang-Ming Li
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China; Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, Hefei 230601, China
| | - Xue-Qiang Zha
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China; Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, Hefei 230601, China
| | - Jian-Ping Luo
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China; Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, Hefei 230601, China.
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8
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Wang S, Han Z, Turchini GM, Wang X, Fang Z, Chen N, Xie R, Zhang H, Li S. Effects of Dietary Phospholipids on Growth Performance, Digestive Enzymes Activity and Intestinal Health of Largemouth Bass ( Micropterus salmoides) Larvae. Front Immunol 2022; 12:827946. [PMID: 35087540 PMCID: PMC8789246 DOI: 10.3389/fimmu.2021.827946] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 12/20/2021] [Indexed: 12/11/2022] Open
Abstract
While the beneficial roles of dietary phospholipids on health status and overall performances of fish larvae have been well demonstrated, the underlying mechanisms remain unclear. To address this gap, the present study was conducted to investigate the effects of dietary phospholipids on growth performance, intestinal development, immune response and microbiota of larval largemouth bass (Micropterus salmoides). Five isonitrogenous and isolipidic micro-diets were formulated to contain graded inclusion levels of phospholipids (1.69, 3.11, 5.23, 7.43 and 9.29%). Results showed that the supplementation of dietary phospholipids linearly improved the growth performance of largemouth bass larvae. The inclusion of dietary phospholipids increased the activity of digestive enzymes, such as lipase, trypsin and alkaline phosphatase, and promoted the expression of tight junction proteins including ZO-1, claudin-4 and claudin-5. Additionally, dietary phospholipids inclusion alleviated the accumulation of intestinal triacylglycerols, and further elevated the activity of lysozyme. Dietary phospholipids inhibited the transcription of some pro-inflammatory cytokines, including il-1β, and tnf-α, but promoted the expression of anti-inflammatory cytokines tgf-β, with these modifications being suggested to be mediated by the p38MAPK/Nf-κB pathway. The analysis of bacterial 16S rRNA V3-4 region indicated that the intestinal microbiota profile was significantly altered at the genus level with dietary phospholipids inclusion, including a decreased richness of pathogenic bacteria genera Klebsiella in larval intestine. In summary, it was showed that largemouth bass larvae have a specific requirement for dietary phospholipids, and this study provided novel insights on how dietary phospholipids supplementation contributes to improving the growth performance, digestive tract development and intestinal health.
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Affiliation(s)
- Shilin Wang
- Research Centre of the Ministry of Agriculture and Rural Affairs on Environmental Ecology and Fish Nutrition, Shanghai Ocean University, Shanghai, China
| | - Zhihao Han
- Research Centre of the Ministry of Agriculture and Rural Affairs on Environmental Ecology and Fish Nutrition, Shanghai Ocean University, Shanghai, China
| | - Giovanni M Turchini
- School of Life and Environmental Sciences, Deakin University, Geelong, VIC, Australia
| | - Xiaoyuan Wang
- Research Centre of the Ministry of Agriculture and Rural Affairs on Environmental Ecology and Fish Nutrition, Shanghai Ocean University, Shanghai, China
| | - Zishuo Fang
- Research Centre of the Ministry of Agriculture and Rural Affairs on Environmental Ecology and Fish Nutrition, Shanghai Ocean University, Shanghai, China
| | - Naisong Chen
- Research Centre of the Ministry of Agriculture and Rural Affairs on Environmental Ecology and Fish Nutrition, Shanghai Ocean University, Shanghai, China
| | - Ruitao Xie
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture and Rural Affairs, Zhanjiang, China
| | - Haitao Zhang
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture and Rural Affairs, Zhanjiang, China
| | - Songlin Li
- Research Centre of the Ministry of Agriculture and Rural Affairs on Environmental Ecology and Fish Nutrition, Shanghai Ocean University, Shanghai, China
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Nanoparticles Carrying NF-κB p65-Specific siRNA Alleviate Colitis in Mice by Attenuating NF-κB-Related Protein Expression and Pro-Inflammatory Cellular Mediator Secretion. Pharmaceutics 2022; 14:pharmaceutics14020419. [PMID: 35214151 PMCID: PMC8874689 DOI: 10.3390/pharmaceutics14020419] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 02/07/2022] [Accepted: 02/09/2022] [Indexed: 12/22/2022] Open
Abstract
Ulcerative colitis is a disease that causes inflammation and ulcers in the colon and which is typically recurrent, and NF-κB proteins are important players during disease progression. Here, we assess the impact of silica-coated calcium phosphate nanoparticles carrying encapsulated siRNA against NF-κB p65 on a murine model of colitis. To this end, nanoparticles were injected intravenously (2.0 mg siRNA/kg body weight) into mice after colitis induction with dextran sulfate sodium or healthy ones. The disease activity index, the histopathological impact on the colon, the protein expression of several NF-κB-associated players, and the mediator secretion (colon tissue, blood) were analyzed. We found that the nanoparticles effectively alleviated the clinical and histopathological features of colitis. They further suppressed the expression of NF-κB proteins (e.g., p65, p50, p52, p100, etc.) in the colon. They finally attenuated the local (colon) or systemic (blood) pro-inflammatory mediator secretion (e.g., TNF-α, IFN-β, MCP-1, interleukins, etc.) as well as the leucocyte load of the spleen and mesenteric lymph nodes. The nanoparticle biodistribution in diseased animals was seen to pinpoint organs containing lymphoid entities (appendix, intestine, lung, etc.). Taken together, the nanoparticle-related silencing of p65 NF-κB protein expression could well be used for the treatment of ulcerative colitis in the future.
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Li M, Lv R, Xu X, Ge Q, Lin S. Tricholoma matsutake-Derived Peptides Show Gastroprotective Effects against Ethanol-Induced Acute Gastric Injury. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:14985-14994. [PMID: 34866395 DOI: 10.1021/acs.jafc.1c07050] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Acute gastric injury caused by ethanol is a frequent disorder of the gastrointestinal tract. In this study, we investigated the potential gastroprotective effects of Tricholoma matsutake-derived peptides against ethanol-triggered acute gastric injury and the associated mechanisms. Peptides SDLKHFPF and SDIKHFPF significantly attenuated the ethanol-induced decrease in GES-1 cell survival (82.39 ± 1.93 and 80.10 ± 1.08% vs 56.58 ± 1.86%), inhibited GES-1 cell apoptosis, and alleviated the ethanol-induced gastric mucosal injury (64.76 ± 3.98 and 49.29 ± 3.25%), ulcer index (3.33 ± 0.47 and 4.67 ± 0.47 vs 6.67 ± 0.47), and histopathological changes in mice. Peptide treatment inhibited the phosphorylation and nuclear translocation of nuclear factor kappa B (NF-κB), the secretion of tumor necrosis factor-α, interleukin-6, and endothelin-1. In addition, T. matsutake peptide pretreatment increased growth factor secretion, upregulated B-cell lymphoma-2, downregulated Bcl-2-associated X (Bax), and cleaved cysteinyl aspartate specific proteinase 3, thereby promoting gastric cell survival. These findings strongly suggest that T. matsutake peptides attenuate ethanol-induced inflammatory responses and apoptosis by suppressing NF-κB signaling activation, thereby enhancing gastric epithelial barrier functions.
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Affiliation(s)
- Mengqi Li
- National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
| | - Renzhi Lv
- National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
| | - Xiaomeng Xu
- National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
| | - Qi Ge
- National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
| | - Songyi Lin
- National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
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11
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Zhou K, Zhang J, Liu C, Ou L, Wang F, Yu Y, Wang Y, Bai S. Sanziguben polysaccharides inhibit diabetic nephropathy through NF-κB-mediated anti-inflammation. Nutr Metab (Lond) 2021; 18:81. [PMID: 34493288 PMCID: PMC8425148 DOI: 10.1186/s12986-021-00601-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 07/08/2021] [Indexed: 01/19/2023] Open
Abstract
Background Sanziguben polysaccharides (SZP) are large amounts of classical Chinese medicines from Sanziguben (SZGB). Moreover, SZGB is a widely applied compound prescription for diabetic nephropathy (DN) treatment, but the role is still unclear. This study initially explores the mechanism of SZP in the treatment of DN. Methods The high-fat diet plus streptozotocin injections were used to replicate the DN models in male C57BL/6 mice. DN mice were divided into five groups: DN mice, DN mice treated with SZP(1.01 or 2.02 g/kg), DN mice treated with SZGB decoction(4.7 g/kg), and DN mice treated with metformin (300 mg/kg). HG and LPS plus TNFα stimulated human tubule epithelial (HK-2) cells to establish an in vitro model and treated with SZP (100 or 200 μg/mL). Results SZP was found to comprise sugar, protein, and uronic acid. Furthermore, SZP alleviated the progression of inflammation in vivo and in vitro by inhibiting the expression of NF-κB. Conclusions NF-κB plays a critical role in the development of DN induced by STZ and HG. Furthermore, SZP can attenuate the NF-κB‐mediated progression of diabetic nephropathy, improve DN through anti-inflammation.
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Affiliation(s)
- Kang Zhou
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Room C306, Pharmaceutical Building, No. 232 Waihuan East Road, Panyu District, Guangzhou, Guangdong, China
| | - Jianing Zhang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Room C306, Pharmaceutical Building, No. 232 Waihuan East Road, Panyu District, Guangzhou, Guangdong, China
| | - Chang Liu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Room C306, Pharmaceutical Building, No. 232 Waihuan East Road, Panyu District, Guangzhou, Guangdong, China
| | - Lijuan Ou
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Room C306, Pharmaceutical Building, No. 232 Waihuan East Road, Panyu District, Guangzhou, Guangdong, China
| | - Fan Wang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Room C306, Pharmaceutical Building, No. 232 Waihuan East Road, Panyu District, Guangzhou, Guangdong, China
| | - Yang Yu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Room C306, Pharmaceutical Building, No. 232 Waihuan East Road, Panyu District, Guangzhou, Guangdong, China
| | - Yumei Wang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Room C306, Pharmaceutical Building, No. 232 Waihuan East Road, Panyu District, Guangzhou, Guangdong, China.
| | - Shasha Bai
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Room C306, Pharmaceutical Building, No. 232 Waihuan East Road, Panyu District, Guangzhou, Guangdong, China.
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12
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Li M, Ge Q, Du H, Jiang P, Bao Z, Chen D, Lin S. Potential Mechanisms Mediating the Protective Effects of Tricholoma matsutake-Derived Peptides in Mitigating DSS-Induced Colitis. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:5536-5546. [PMID: 33955220 DOI: 10.1021/acs.jafc.1c01908] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Intestinal barrier dysfunction and inflammatory cytokine secretion play crucial roles in inflammatory bowel disease (IBD). Herein, we investigated the protective effects of Tricholoma matsutake-derived peptides SDIKHFPF and SDLKHFPF against dextran sulfate sodium-induced colitis. Both peptides alleviated colitis signs, including diarrhea, weight loss, bloody stools, colon shortening, and histopathological changes, while reducing mucus destruction, goblet cell exhaustion, and intestinal permeability. SDIKHFPF and SDLKHFPF protected the barrier function by promoting the expression of tight junction (TJ) zonula occludens-1 and occludin within the colon, as well as attenuating colonic inflammation through myeloperoxidase and pro-inflammatory cytokine suppression. Western blotting indicated that the peptides suppressed myosin light chain kinase (MLCK) and nuclear factor kappa B (NF-κB) levels, inhibiting MLC phosphorylation. SDLKHFPF was more potent than SDIKHFPF. These findings suggest that peptide SDLKHFPF mitigates colitis by regulating TJ protein expression and pro-inflammatory cytokine production via NF-κB/MLCK/p-MLC signaling, improving the barrier function.
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Affiliation(s)
- Mengqi Li
- National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
| | - Qi Ge
- National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
| | - Hanting Du
- National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
| | - Pengfei Jiang
- National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
| | - Zhijie Bao
- National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
| | - Dong Chen
- National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
| | - Songyi Lin
- National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
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Huang D, Maulu S, Ren M, Liang H, Ge X, Ji K, Yu H. Dietary Lysine Levels Improved Antioxidant Capacity and Immunity via the TOR and p38 MAPK Signaling Pathways in Grass Carp, Ctenopharyngodon idellus Fry. Front Immunol 2021; 12:635015. [PMID: 33717179 PMCID: PMC7947207 DOI: 10.3389/fimmu.2021.635015] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 01/11/2021] [Indexed: 12/30/2022] Open
Abstract
An 8-week rearing trial was designed to appraise the dietary lysine levels on intestinal antioxidant capacity and immunity of grass carp fry. Six practical diets were prepared with graded levels of lysine (1.44, 1.79, 1.97, 2.44, 2.56 and 2.87% dry matter), and these diets were fed to grass carp fry. The results showed that the activities of intestinal antioxidant factors including catalase and glutathione peroxidase were markedly improved by the 2.44% dietary lysine compared with the control diet (1.44% dietary lysine) (P < 0.05). In terms of antioxidants, compared with the control diet, the 2.44% diet markedly upregulated the mRNA expression levels of target of rapamycin, S6 kinase1 and nuclear factor erythroid 2-related factor 2 pathway-related antioxidant genes, containing catalase and glutathione peroxidase 1α (P < 0.05) and downregulated the mRNA levels of Kelch-like ECH-associated protein 1 (P > 0.05). The mRNA levels of 4E-binding protein 2 showed the opposite trend compared with those of target of rapamycin, and the minimum value was observed in the group of 1.97% dietary lysine (P < 0.05). In terms of immunity, compared with the 1.44% diet, the 2.44% diet markedly suppressed the intestinal p38 mitogen-activated protein kinase and interferon γ2 mRNA levels (P < 0.05). Moreover, nuclear factor-kappa B p65, tumor necrosis factor α, interleukin 6, interleukin 8, and interleukin 15 mRNA levels all exhibited the same trend as p38 mitogen-activated protein kinase and interferon γ2; however, the difference among all the lysine treatments groups was not significant (P > 0.05). The anti-inflammatory cytokines transforming growth factor β2 and interleukin 4/13B mRNA levels in the intestine were remarkably upregulated by high dietary lysine levels (2.56 and 2.87%) (P < 0.05), and when the dietary lysine level reached 2.44%, the interleukin 4/13A mRNA levels were strikingly increased (P < 0.05). Overall, the data suggested that 2.44% dietary lysine could strengthen the immune and antioxidant capacities of grass carp fry via activating the target of rapamycin (TOR) signaling pathway, and suppressing the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway, which then improve the survival rate.
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Affiliation(s)
- Dongyu Huang
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, China
| | - Sahya Maulu
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, China
| | - Mingchun Ren
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, China
- Key Laboratory for Genetic Breeding of Aquatic Animals and Aquaculture Biology, Freshwater Fisheries Research Center (FFRC), Chinese Academy of Fishery Sciences (CAFS), Wuxi, China
| | - Hualiang Liang
- Key Laboratory for Genetic Breeding of Aquatic Animals and Aquaculture Biology, Freshwater Fisheries Research Center (FFRC), Chinese Academy of Fishery Sciences (CAFS), Wuxi, China
| | - Xianping Ge
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, China
- Key Laboratory for Genetic Breeding of Aquatic Animals and Aquaculture Biology, Freshwater Fisheries Research Center (FFRC), Chinese Academy of Fishery Sciences (CAFS), Wuxi, China
| | - Ke Ji
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, China
| | - Heng Yu
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, China
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Li MY, Gao CS, Du XY, Zhao L, Niu XT, Wang GQ, Zhang DM. Effect of sub-chronic exposure to selenium and astaxanthin on Channa argus: Bioaccumulation, oxidative stress and inflammatory response. CHEMOSPHERE 2020; 244:125546. [PMID: 32050342 DOI: 10.1016/j.chemosphere.2019.125546] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 12/02/2019] [Accepted: 12/03/2019] [Indexed: 06/10/2023]
Abstract
Selenium (Se) is the most common micronutrient and that becomes toxic when present at higher concentrations in aquatic environments. Astaxanthin (AST) has been documented to possess antioxidant and anti-inflammatory properties. The aim of this study was to explore the potential of dietary AST and Se exposure on oxidative stress, and inflammatory response in Channa argus. After acclimation, 540 fish were randomly distributed into nine groups housed in twenty-seven glass tanks. The fish were exposed for 8 weeks to waterborne Se at 0, 100 and 200 μg L-1 or dietary AST at 0, 50 and 100 mg kg-1. The results shown that Se accumulation in the kidney, liver, spleen, intestine and gill were significantly increased following Se exposure, dietary 50 and 100 mg kg-1 AST supplementation decreased the accumulation of Se in the kidney, liver, spleen, and intestine. In addition, AST supplementation can decrease oxidative stress and inflammatory response in the liver and spleen following exposure to waterborne Se. These results indicate that AST has the potential to alleviate the effects of Se toxicity in C. argus.
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Affiliation(s)
- Mu-Yang Li
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, 130118, China; Ministry of Education Laboratory of Animal Production and Quality Security, Jilin Agricultural University, Changchun, Jilin, 130118, China; Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, 130118, China; Jilin Provincial Key Laboratory of Animal Nutrition and Feed Science, Jilin Agricultural University, Changchun, Jilin, 130118, China
| | - Chun-Shan Gao
- Freshwater Fisheries Research Institute of Jilin Province, Changchun, Jilin, 130000, China
| | - Xiao-Yan Du
- Freshwater Fisheries Research Institute of Jilin Province, Changchun, Jilin, 130000, China
| | - Lei Zhao
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, 130118, China; Ministry of Education Laboratory of Animal Production and Quality Security, Jilin Agricultural University, Changchun, Jilin, 130118, China; Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, 130118, China; Jilin Provincial Key Laboratory of Animal Nutrition and Feed Science, Jilin Agricultural University, Changchun, Jilin, 130118, China
| | - Xiao-Tian Niu
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, 130118, China; Ministry of Education Laboratory of Animal Production and Quality Security, Jilin Agricultural University, Changchun, Jilin, 130118, China; Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, 130118, China; Jilin Provincial Key Laboratory of Animal Nutrition and Feed Science, Jilin Agricultural University, Changchun, Jilin, 130118, China
| | - Gui-Qin Wang
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, 130118, China; Ministry of Education Laboratory of Animal Production and Quality Security, Jilin Agricultural University, Changchun, Jilin, 130118, China; Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, 130118, China; Jilin Provincial Key Laboratory of Animal Nutrition and Feed Science, Jilin Agricultural University, Changchun, Jilin, 130118, China.
| | - Dong-Ming Zhang
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, 130118, China; Ministry of Education Laboratory of Animal Production and Quality Security, Jilin Agricultural University, Changchun, Jilin, 130118, China; Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University, Changchun, Jilin, 130118, China; Jilin Provincial Key Laboratory of Animal Nutrition and Feed Science, Jilin Agricultural University, Changchun, Jilin, 130118, China.
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15
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Lu PD, Zhao YH. Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines. Chin Med 2020; 15:15. [PMID: 32063999 PMCID: PMC7011253 DOI: 10.1186/s13020-020-0296-z] [Citation(s) in RCA: 88] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 01/30/2020] [Indexed: 12/15/2022] Open
Abstract
Nuclear factor-kappa B (NF-κB) is a kind of multi-functional nuclear transcription factor involved in regulating gene transcription to influence pathological evolution of inflammatory and immune diseases. Numerous literature evidence that NF-κB pathway plays an essential role in pathogenic development of ulcerative colitis (UC). UC is a chronic non-specific inflammatory bowel disease, and until now, therapeutic agents for UC including aminosalicylates, corticosteroids and immune inhibitors still cannot exert satisfied effects on patients. In recent years, Chinese medicines suggest the advantages of alleviating symptoms and signs, decreasing side-effects and recurrence, whose one of mechanisms is related to regulation of NF-κB pathway. In this review, we categorize Chinese medicines according to their traditional therapeutic functions, and summarize the characteristics of Chinese medicines targeting NF-κB pathway in UC treatment. It indicates that 85 kinds of Chinese medicines’ compounds and formulae can directly act on NF-κBp65; while 58 Chinese medicines’ ingredients and formulae indirectly suppress NF-κBp65 by regulation of its upstream or other related pathways. Moreover, by the analysis of Chinese medicines’ category based on their traditional functions, we conclude the category of dampness-drying and detoxificating medicine targeting NF-κB pathway accounts for primary status for amelioration of UC. Simultaneously, this review also contributes to the choices of Chinese medicine category and provides curative potential of Chinese medicines for clinical UC treatment.
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Affiliation(s)
- Peng-De Lu
- 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yong-Hua Zhao
- 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078 Macao, Special Administrative Region of China
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Bian Y, Dong Y, Sun J, Sun M, Hou Q, Lai Y, Zhang B. Protective Effect of Kaempferol on LPS-Induced Inflammation and Barrier Dysfunction in a Coculture Model of Intestinal Epithelial Cells and Intestinal Microvascular Endothelial Cells. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:160-167. [PMID: 31825618 DOI: 10.1021/acs.jafc.9b06294] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of intestinal mucosa and submucosa, characterized by the disruption of the intestinal epithelial barrier, increased production of inflammatory mediators, and excessive tissue injury. Intestinal epithelial cells, as well as microvascular endothelial cells, play important roles in IBD. To study the potential effects of kaempferol in IBD progress, we established a novel epithelial-endothelial cells coculture model to investigate the intestinal inflammation and barrier function. Data demonstrated an obvious increased transepithelial electrical resistance (TEER) (1222 ± 60.40 Ω cm2 vs 1371 ± 38.77 Ω cm2), decreased flux of FITC (180.8 ± 20.06 μg/mL vs 136.7 ± 14.78 μg/mL), and up-regulated occludin and claudin-2 expression in Caco-2 that was specifically cocultured with endothelial cells. Meanwhile, 80 μM kaempferol alleviated the drop of TEER, the increase of FITC flux, and the overexpression of interleukin-8 (IL-8) induced by 1 μg/mL lipopolysaccharide (LPS). Additionally, kaempferol also ameliorated the LPS-induced decrease of protein expression of zonula occludens-1 (ZO-1), occludin, and claudin-2, together with the inhibited protein expressions of the phosphorylation level of NF-κB and I-κB induced by LPS. Our results suggest that kaempferol alleviates the IL-8 secretion and barrier dysfunction of the Caco-2 monolayer in the LPS-induced epithelial-endothelial coculture model via inhibiting the NF-κB signaling pathway activation.
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Affiliation(s)
- Yifei Bian
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology , China Agricultural University , Yuanmingyuan West Road , Haidian District, Beijing , 100193 , China
| | - Yuanyang Dong
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology , China Agricultural University , Yuanmingyuan West Road , Haidian District, Beijing , 100193 , China
| | - Jingjing Sun
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology , China Agricultural University , Yuanmingyuan West Road , Haidian District, Beijing , 100193 , China
| | - Meng Sun
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology , China Agricultural University , Yuanmingyuan West Road , Haidian District, Beijing , 100193 , China
| | - Qihang Hou
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology , China Agricultural University , Yuanmingyuan West Road , Haidian District, Beijing , 100193 , China
| | - Yujiao Lai
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology , China Agricultural University , Yuanmingyuan West Road , Haidian District, Beijing , 100193 , China
| | - Bingkun Zhang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology , China Agricultural University , Yuanmingyuan West Road , Haidian District, Beijing , 100193 , China
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Li W, Gao M, Han T. Lycium barbarum polysaccharides ameliorate intestinal barrier dysfunction and inflammation through the MLCK-MLC signaling pathway in Caco-2 cells. Food Funct 2020; 11:3741-3748. [PMID: 32314770 DOI: 10.1039/d0fo00030b] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Impairment of the intestinal barrier often occurs in inflammatory bowel diseases, and pro-inflammatory factors play a vital role in the pathogenesis of intestinal diseases.
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Affiliation(s)
- Wei Li
- Shanghai Tenth People's Hospital
- Tongji University School of Medicine
- Shanghai 200072
- China
| | - Mingbo Gao
- Shanghai Tenth People's Hospital
- Tongji University School of Medicine
- Shanghai 200072
- China
| | - Ting Han
- Shanghai Tenth People's Hospital
- Tongji University School of Medicine
- Shanghai 200072
- China
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18
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Zhao HM, Liu Y, Huang XY, Liu XK, Chen F, Zhang XY, Liu FC, Lu XY, Wang Y, Liu DY. Pharmacological mechanism of Sishen Wan ® attenuated experimental chronic colitis by inhibiting wnt/β-catenin pathway. JOURNAL OF ETHNOPHARMACOLOGY 2019; 240:111936. [PMID: 31078692 DOI: 10.1016/j.jep.2019.111936] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Revised: 04/05/2019] [Accepted: 05/04/2019] [Indexed: 06/09/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Sishen Wan (SSW) is a commercial and frequently used Chinese patent medicine listed in the Chinese Pharmacopeia, which is usually used to treat chronic colitis. AIM OF THE STUDY We explored the pharmacological mechanism of Sishen Wan attenuated experimental chronic colitis by inhibiting Wnt/β-catenin pathway. MATERIALS AND METHODS Experimental chronic colitis was induced by trinitrobenzene sulfonic acid (TNBS). The therapeutic effect of SSW were analyzed by index of colonic weight, colonic length, pathological score. Cytokines expression were analyzed by ELISA, while the apoptosis level was checked by TUNEL staining. These proteins of Wnt/β-catenin signaling pathway was analyzed by Western blot assay. RESULTS Rats with TNBS-induced chronic colitis were treated by SSW for 10 days. The efficacy of SSW was demonstrated by improved macroscopic and microscopic colonic damage. SSW increased the level of ATP in colonic mucosa, while SSW inhibited β-catenin, ubiquitination of Nemo-like-kinase-associated ring finger protein and T-cell factor, and expression of Wnt/β-catenin downstream proteins (including c-Myc, cyclo-oxygenase-2, cyclin D1, survivin, signal transducer and activator of transcription 3 and zipper-interacting protein kinase), and improved lymphoid enhancer factor ubiquitination and β-TrCP activity, followed by excessive apoptosis of colonic epithelial cells. CONCLUSIONS SSW effectively attenuated experimental chronic colitis induced by TNBS, which was realized by inhibition of the Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Hai-Mei Zhao
- School of Basic Medical Sciences, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Yi Liu
- Department of Postgraduate, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Xiao-Ying Huang
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Xue-Ke Liu
- Department of Postgraduate, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Fang Chen
- Department of Postgraduate, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Xiao-Yun Zhang
- Department of Postgraduate, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Fu-Chun Liu
- Department of Postgraduate, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Xiu-Yun Lu
- Science and Technology College, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Yao Wang
- School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, 150040, Heilongjiang Province, China.
| | - Duan-Yong Liu
- Science and Technology College, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China; Key Laboratory of Pharmacology of Traditional Chinese Medicine in Jiangxi, Nanchang, 330004, Jiangxi Province, China.
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Polysaccharide from Scutellaria baicalensis Georgi ameliorates colitis via suppressing NF-κB signaling and NLRP3 inflammasome activation. Int J Biol Macromol 2019; 132:393-405. [DOI: 10.1016/j.ijbiomac.2019.03.230] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Revised: 03/14/2019] [Accepted: 03/29/2019] [Indexed: 02/07/2023]
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Yan Y, Wang P, Sun Y, Dong Y, Xing J. Potential Mechanisms of 3, 4-Oxo-Isopropylidene-Shikimic Acid in Ameliorating 2, 4, 6-Trinitrobenzenesulfonic Acid-Induced Colitis in Rats. J Interferon Cytokine Res 2019; 39:554-563. [PMID: 31120312 DOI: 10.1089/jir.2019.0064] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Previously, we reported that 3, 4-oxo-isopropylidene-shikimic acid (ISA) has therapeutic potential in experimental colitis in rats. This study aimed to elucidate the potential mechanisms of ISA on the inflammatory response in rats with 2, 4, 6-trinitrobenzenesulfonic acid-induced colitis. After the induction of colitis, rats were orally administered ISA for 12 days. Then, the expression levels of inflammatory cytokines, cell adhesion molecules, and matrix metalloproteinase (MMP) in the blood and colon tissues, and the protein level of nuclear factor kappa B (NF-κB) p65 in cytoplasm and nucleus of colon tissues were evaluated. As a result, an enhanced inflammatory response was observed in rats with experimental colitis. However, the treatment with ISA significantly ameliorated the inflammatory response, which was manifested as a significant decrease in the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, IL-8, TNF-α mRNA, P-selectin, E-selectin, intercellular cell adhesion molecule-1, MMP9 and MMP9 mRNA in rat blood and colon tissues, respectively, and a significant decrease in the levels of IFN-γ/IL-4, and the NF-κBp65 activity coefficient. Therefore, the therapeutic effect of ISA on experimental colitis may be related to its inhibitory effect on the expression of cytokines, adhesion molecules, and MMP9, which may be involved in the inhibition of the activation and nuclear translocation of NF-κBp65.
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Affiliation(s)
- Yan Yan
- Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Shaanxi, China
| | - Pengchong Wang
- Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Shaanxi, China
| | - Ying Sun
- Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Shaanxi, China
| | - Yalin Dong
- Department of Pharmacy, the First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China
| | - Jianfeng Xing
- Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Shaanxi, China
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Ni PJ, Feng L, Jiang WD, Wu P, Liu Y, Jiang J, Kuang SY, Tang L, Tang WN, Zhou XQ. Impairing of gill health through decreasing immune function and structural integrity of grass carp (Ctenopharyngodon idella) fed graded levels dietary lipids after challenged with Flavobacterium columnare. FISH & SHELLFISH IMMUNOLOGY 2019; 86:922-933. [PMID: 30590156 DOI: 10.1016/j.fsi.2018.12.049] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Revised: 11/22/2018] [Accepted: 12/23/2018] [Indexed: 06/09/2023]
Abstract
The current study conducted to investigate the hypothesis that low or excess levels of lipids increased the gill rot morbidity through impairing the immune function and structural integrity in the gill of grass carp (Ctenopharyngodon idella). A total of 540 young grass carp with an average initial weight of 261.41 ± 0.53 g were fed diets containing six graded levels of lipids at 0.59%, 2.14%, 3.60%, 5.02%, 6.66% and 8.01% diets for 8 weeks. After the growth trial, fish were challenged with Flavobacterium columnare for 3 days. The results indicated that compared with optimal lipids supplementation (2.14%-8.01% lipids diets), low or excess levels of lipids impaired fish immune function through declining the activities of humoral compounds, down-regulated the mRNA levels of anti-inflammatory cytokines, inhibitor of κBα (IκBα) and ribosomal p70S6 kinase (S6K1), and up-regulated pro-inflammatory cytokines, nuclear factor κB p65 (NF-κB p65) (not p52), IκB kinase α (IKKα) (not IKKβ), IKKγ and eIF4E-binding protein (4EBP) in the gill of young grass carp. In addition, low or excess levels of lipids decreased young grass carp physical barrier function through down-regulating the mRNA levels of ZO-1 (rather than ZO-2b), Claudin b, c, 3, 12, 15a, 15b, 7b, 7a and Occludin through MAPKK 6/p38 MAPK/MLCK signaling molecules, decreasing antioxidant ability via Kelch-like ECH-associating protein 1a (Keap1a)/NF-E2-related factor 2 (Nrf2) signaling molecules, and down-regulating the mRNA levels of B-cell lymphoma-2 (Bcl-2) and inhibitor of apoptosis protein (IAP) and up-regulating the mRNA levels of apoptotic protease activating factor-1 (Apaf-1), Caspase-3, -8 and -9 and Fas ligand (FasL) in the gill of grass carp. Based on the quadratic regression analysis for the gill rot morbidity, C3 and MDA contents, the dietary lipids requirements for young grass carp have been estimated to be 5.60%, 6.01% and 4.58% diets.
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Affiliation(s)
- Pei-Jun Ni
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Lin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Wei-Dan Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Pei Wu
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Yang Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Jun Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Sheng-Yao Kuang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Ling Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Wu-Neng Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Xiao-Qiu Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China.
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Kong L, Cheng SY, Xiang XJ, Liu WS, Yu DH, Yang YO, Zhou J, Huang F, Dong GF. Dietary conjugated linoleic acid modulates morphology, selective immune parameters, and gene expressions in the intestine of grass carp. FISH & SHELLFISH IMMUNOLOGY 2019; 86:536-548. [PMID: 30508674 DOI: 10.1016/j.fsi.2018.11.071] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2018] [Revised: 11/23/2018] [Accepted: 11/29/2018] [Indexed: 06/09/2023]
Abstract
Conjugated linoleic acid (CLA) has been shown to exhibit anti-inflammatory properties in the intestine in mammals. However, the effect of CLA on intestinal immune response in fish is still unknown. Therefore, a 65-day growth trial was conducted to investigate the effects of dietary conjugated linoleic acid (CLA) on morphology, selective immune parameters, and gene expressions in the intestine of grass carp. Seven isonitrogenous and isolipidic diets were formulated as follows: 0 (control), 0.5 (CLA0.5), 1 (CLA1), 1.5 (CLA1.5), 2 (CLA2), 2.5 (CLA2.5), and 3 (CLA3) g CLA per 100g of feed. RESULTS: showed that dietary supplementation of 1.5-3% CLA significantly (P < 0.05) increased the fold and enterocyte heights in the PI and MI of grass carp. Complement 3 (C3) and immunoglobulin M (IgM) contents in three intestinal segments were significantly (P < 0.05) higher in fish fed with CLA1.5 to CLA2.5 diets compared to fish fed the control diet. CLA1.5 to CLA2.5 diets significantly (P < 0.05) increased the mRNA expression levels of anti-inflammatory cytokines (IL-10 and TGFβ1) and significantly (P < 0.05) reduced the mRNA expression levels of pro-inflammatory cytokines (IL-1β, IL-8, and TNF-α) in the PI, MI, and DI. This improved expression of anti-inflammatory cytokines and the inhibited expression of pro-inflammatory cytokines in the intestine of grass carp, might be mediated via TLR4/NF-κB-signaling pathway. Our results suggested that CLA1.5 to CLA2 diets improved intestinal morphology, increased the expression of anti-inflammatory cytokines, and inhibited the expression of pro-inflammatory cytokines in the intestine of grass carp. In conclusion, dietary supplementation of 1.5%-2% CLA show the anti-inflammatory therapeutic potential in the intestine of grass carp. The anti-inflammatory therapeutic potential of CLA might be mediated via TLR4/NF-κB-signaling pathway.
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Affiliation(s)
- Long Kong
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, Hubei, 430023, China
| | - Shi-Yan Cheng
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, Hubei, 430023, China
| | - Xiao-Jun Xiang
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, Hubei, 430023, China
| | - Wen-Shu Liu
- Institute of Animal Husbandry and Veterinary, Jiangxi Academy of Agricultural Science, Nanchang, Jiangxi, 330200, China
| | - Deng-Hang Yu
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, Hubei, 430023, China
| | - Yan-Ou Yang
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, 230000, China
| | - Jiancheng Zhou
- Wuhan DBN Aquaculture Technology Co. LTD, Wuhan, Hubei, 430090, China
| | - Feng Huang
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, Hubei, 430023, China
| | - Gui-Fang Dong
- Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, Hubei, 430023, China.
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Bian Y, Liu P, Zhong J, Hu Y, Fan Y, Zhuang S, Liu Z. Kaempferol inhibits multiple pathways involved in the secretion of inflammatory mediators from LPS‑induced rat intestinal microvascular endothelial cells. Mol Med Rep 2018; 19:1958-1964. [PMID: 30569099 DOI: 10.3892/mmr.2018.9777] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Accepted: 11/08/2018] [Indexed: 11/06/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic, idiopathic inflammatory disease of the small and/or large intestine. Endothelial expression of inflammatory mediators, including cytokines and adhesion molecules, serves a critical role in the initiation and progression of IBD. The dietary flavonoid, kaempferol, has been reported to inhibit expression of inflammatory mediators; however, the underlying mechanisms require further investigation. In the present study, a novel molecular mechanism of kaempferol against IBD was identified. The potential anti‑inflammatory effect of kaempferol in a cellular model of intestinal inflammation was assessed using lipopolysaccharide (LPS)‑induced rat intestinal microvascular endothelial cells (RIMVECs), and an underlying key molecular mechanism was identified. RIMVECs were pretreated with kaempferol of various concentrations (12.5, 25 and 50 µM) followed by LPS (10 µg/ml) stimulation. ELISA was used to examine the protein levels of tumor necrosis factor‑α (TNF‑α), interleukin‑1β (IL‑1β), IL‑6, intercellular adhesion molecule-1 (ICAM‑1) and vascular cell adhesion molecule-1 (VCAM‑1) in the supernatant. Protein expression levels of Toll‑like receptor 4 (TLR4), nuclear factor‑κB (NF‑κB) p65, inhibitor of NF‑κB, mitogen‑activated protein kinase p38 and signal transducer and activator of transcription (STAT) in cells were measured by western blotting. Kaempferol significantly reduced the overproduction of TNF‑α, IL‑1β, interleukin‑6, ICAM‑1 and VCAM‑1 induced by LPS, indicating the negative regulation of kaempferol in TLR4, NF‑κB and STAT signaling underlying intestinal inflammation. The present results provide support for the potential use of kaempferol as an effective therapeutic agent for IBD treatment.
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Affiliation(s)
- Yifei Bian
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, P.R. China
| | - Ping Liu
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, P.R. China
| | - Jia Zhong
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, P.R. China
| | - Yusheng Hu
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, P.R. China
| | - Yingsai Fan
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, P.R. China
| | - Shen Zhuang
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, P.R. China
| | - Zhongjie Liu
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, P.R. China
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Bioaccumulation, oxidative stress, immune responses and immune-related genes expression in northern snakehead fish, Channa argus, exposure to waterborne selenium. Mol Biol Rep 2018; 46:947-955. [DOI: 10.1007/s11033-018-4550-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Accepted: 11/30/2018] [Indexed: 10/27/2022]
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25
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Bian Y, Liu P, Zhong J, Hu Y, Zhuang S, Fan K, Liu Z. Quercetin Attenuates Adhesion Molecule Expression in Intestinal Microvascular Endothelial Cells by Modulating Multiple Pathways. Dig Dis Sci 2018; 63:3297-3304. [PMID: 30076503 DOI: 10.1007/s10620-018-5221-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Accepted: 07/20/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND In inflammatory bowel disease, activation of microvascular endothelial cells and adhesion of immune cells are required for the initiation and maintenance of inflammation. We evaluated the effects and mechanisms of quercetin, a flavone identified in a wide variety of dietary sources, in LPS-induced rat intestinal microvascular endothelial cells (RIMVECs). METHODS RIMVECs were pretreated with quercetin of various concentrations (20, 40 and 80 μM) followed by LPS (10 μg/ml) stimulation. ELISA was used to examine protein levels of intercellular adhesion molecules-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the supernatant. Protein levels of Toll-like receptor 4 (TLR4), nuclear transcription factor kappa B (NF-κB) p65, inhibitors of NF-κB (IκB-α), extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK) p38 and signal transducer and activator of transcription (STAT) in cells were measured by Western blot. RESULTS Quercetin significantly suppressed protein levels of ICAM-1 and VCAM-1 induced by LPS. Quercetin also inhibited TLR4 expression, NF-κB p65, ERK, JNK and STAT phosphorylation and decreased IκB-α degradation. Moreover, the MAPK p38 signal does not contribute to the anti-inflammatory effects on RIMVECs, although LPS significantly increases its phosphorylation. CONCLUSIONS These results indicate that quercetin may have an anti-inflammatory effect by inhibiting expression of ICAM-1 and VCAM-1 in RIMVECs by suppressing TLR4, NF-κB, ERK, JNK and STAT but not the p38 signaling pathway.
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Affiliation(s)
- Yifei Bian
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Yuan Ming Yuan West Road No. 2, Haidian District, Beijing, 100193, People's Republic of China
| | - Ping Liu
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Yuan Ming Yuan West Road No. 2, Haidian District, Beijing, 100193, People's Republic of China
| | - Jia Zhong
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Yuan Ming Yuan West Road No. 2, Haidian District, Beijing, 100193, People's Republic of China
| | - Yusheng Hu
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Yuan Ming Yuan West Road No. 2, Haidian District, Beijing, 100193, People's Republic of China
| | - Shen Zhuang
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Yuan Ming Yuan West Road No. 2, Haidian District, Beijing, 100193, People's Republic of China
| | - Kai Fan
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Yuan Ming Yuan West Road No. 2, Haidian District, Beijing, 100193, People's Republic of China
| | - Zhongjie Liu
- Division of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Yuan Ming Yuan West Road No. 2, Haidian District, Beijing, 100193, People's Republic of China.
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Vinpocetine Ameliorates Acetic Acid-Induced Colitis by Inhibiting NF-κB Activation in Mice. Inflammation 2018; 41:1276-1289. [PMID: 29633103 DOI: 10.1007/s10753-018-0776-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
The idiopathic inflammatory bowel diseases (IBD) comprise two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. Recruited neutrophils and macrophages contribute to intestinal tissue damage via production of ROS and NF-κB-dependent pro-inflammatory cytokines. The introduction of anti-TNF-α therapies in the treatment of IBD patients was a seminal advance. This therapy is often limited by a loss of efficacy due to the development of adaptive immune response, underscoring the need for novel therapies targeting similar pathways. Vinpocetine is a nootropic drug and in addition to its antioxidant effect, it is known to have anti-inflammatory and analgesic properties, partly by inhibition of NF-κB and downstream cytokines. Therefore, the present study evaluated the effect of the vinpocetine in a model of acid acetic-induced colitis in mice. Treatment with vinpocetine reduced edema, MPO activity, microscopic score and macroscopic damage, and visceral mechanical hyperalgesia. Vinpocetine prevented the reduction of colonic levels of GSH, ABTS radical scavenging ability, and normalized levels of anti-inflammatory cytokine IL-10. Moreover, vinpocetine reduced NF-κB activation and thereby NF-κB-dependent pro-inflammatory cytokines IL-1β, TNF-α, and IL-33 in the colon. Thus, we demonstrate for the first time that vinpocetine has anti-inflammatory, antioxidant, and analgesic effects in a model of acid acetic-induced colitis in mice and deserves further screening to address its suitability as an approach for the treatment of IBD.
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Ubale RV, Shastri PN, Oettinger C, D’Souza MJ. Pulmonary Administration of Microparticulate Antisense Oligonucleotide (ASO) for the Treatment of Lung Inflammation. AAPS PharmSciTech 2018; 19:1908-1919. [PMID: 29663290 DOI: 10.1208/s12249-018-1002-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 03/19/2018] [Indexed: 01/01/2023] Open
Abstract
Targeted delivery to the lung for controlling lung inflammation is an area that we have explored in this study. The purpose was to use microparticles containing an antisense oligonucleotide (ASO) to NF-κB to inhibit the production of proinflammatory cytokines. Microparticles were prepared using the B-290 Buchi Spray Dryer using albumin as the microparticle matrix. Physicochemical characterization of the microparticles showed the size ranged from 2 to 5 μm, the charge was - 38.4 mV, and they had a sustained release profile over 72 h. Uptake of FITC-labeled ASO-loaded microparticles versus FITC-labeled ASO solution by RAW264.7 murine macrophage cells was 5-10-fold higher. After pulmonary delivery of microparticles to Sprague-Dawley rats, the microparticles were uniformly distributed throughout the lung and were retained in the lungs until 48 h. Serum cytokine (TNF-α and IL-1β) levels of rats after induction of lung inflammation by lipopolysaccharide were measured until 72 h. Animals receiving ASO-loaded microparticles were successful in significantly controlling lung inflammation during this period as compared to animals receiving no treatment. This study was successful in proving that microparticulate ASO therapy was capable of controlling lung inflammation.
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Liu PF, Du Y, Meng L, Li X, Liu Y. ALDH7A1 is a protein that protects Atlantic salmon against Aeromonas salmonicida at the early stages of infection. FISH & SHELLFISH IMMUNOLOGY 2017; 70:30-39. [PMID: 28867386 DOI: 10.1016/j.fsi.2017.08.043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 07/12/2017] [Accepted: 08/29/2017] [Indexed: 06/07/2023]
Abstract
Aldehyde dehydrogenases (ALDHs) belong to a super-family of detoxifying proteins and perform a significant role in developing epithelial homeostasis, protecting cells from toxic aldehydes and drug resistance. However, the activity and function of these detoxifying proteins remain unknown, especially in fish. In our research, we aimed to study functions of aldehyde dehydrogenase 7A1 (ALDH7A1) in Atlantic salmon infected by Aeromonas salmonicida. Recombinant ALDH7A1 (rALDH7A1) was verified by SDS-PAGE and western blot. The molecular mass of the deduced amino acid sequence of rALDH7A1 is 58.9 kDa with an estimated pI of 7.09. Only a low complexity region (141yvegvgevqeyvdv153) without a signal peptide existed in rALDH7A1. Results of ELISA indicated that rALDH7A1 exhibited apparent binding activities with A. salmonicida and its expression was highest in fish kidney. A Real-Time PCR (qRT-PCR) assay in kidneys confirmed that fish in this experiment were authentically infected and bacterial loads in rALDH7A1-adminsitered fish were significantly reduced at an early stage of infection. Meanwhile, we found the mRNA expression of NF-kβ, P-38 MAPK, caspase-3 and TNF-α were mainly up-regulated at 72 h in the kidneys and livers of highly infected fish injected with rALDH7A1, and the same variation trend existed in fish spleens at 12 h. Consistent with these observations, neutralization experiments in vivo indicated that rALDH7A1 could obviously reduce the death rate compared to the BSA and control group. Taken together, we concluded that rALDH7A1 could act in host immune defense against bacterial infection and decrease the mortality rate of Atlantic salmon at early stages of infection with A. salmonicida.
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Affiliation(s)
- Peng-Fei Liu
- Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China; University of Chinese Academy of Sciences, Beijing, 100039, China.
| | - Yishuai Du
- Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China
| | - Lingjie Meng
- Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China; University of Chinese Academy of Sciences, Beijing, 100039, China
| | - Xian Li
- Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China
| | - Ying Liu
- Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China; Dalian Ocean University, Dalian, China.
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29
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Jiang WD, Tang RJ, Liu Y, Wu P, Kuang SY, Jiang J, Tang L, Tang WN, Zhang YA, Zhou XQ, Feng L. Impairment of gill structural integrity by manganese deficiency or excess related to induction of oxidative damage, apoptosis and dysfunction of the physical barrier as regulated by NF-κB, caspase and Nrf2 signaling in fish. FISH & SHELLFISH IMMUNOLOGY 2017; 70:280-292. [PMID: 28887111 DOI: 10.1016/j.fsi.2017.09.022] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 08/24/2017] [Accepted: 09/05/2017] [Indexed: 06/07/2023]
Abstract
This study is for the first time to explore the possible effects of dietary manganese (Mn) on structural integrity and the related signaling in the gills of fish. Grass carp (Ctenopharyngodon idella) were fed with six diets containing graded levels of Mn [3.65-27.86 mg Mn/kg diet] for 8 weeks. The results firstly demonstrated that Mn deficiency aggravated inflammation indicated by up-regulation of pro-inflammatory cytokines (tumour necrosis factor α, interleukin 8, and interleukin 1β mRNA levels) and down-regulation of anti-inflammatory cytokines (interleukin 10, transforming growth factor-β1) mRNA levels, which might be partially related to the up-regulation of nuclear factor kappa B (NF-κB p65) and down-regulation of nuclear inhibitor factor κBα (iκBα) mRNA levels in the gills of fish. Meanwhile, Mn deficiency caused DNA fragmentation, which might be partially associated with the up-regulation of the apoptosis signaling (caspase-3, caspase-8 and caspase-9) in the gills of fish. Furthermore, Mn deficiency-caused apoptosis might be partly related to the increases of oxidative damage that indicated by increases of lipid peroxidation and protein oxidation, and decreases of antioxidant enzyme activities [included Mn superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)]. However, Mn deficiency only down-regulated MnSOD and GST mRNA levels, which might be partially related to the up-regulation of NF-E2-related factor-2 (Nrf2) inhibitor (Keap1), and only down-regulated the gene expression of claudin-b and claudin-15 to disrupt the TJ in the gills of fish. Excessive Mn led to negative effects on partial parameters studied in the gills of fish. The optimal levels of Mn based on protecting against ROS, MDA and PC in the gills of grass carp were 17.04, 16.86 and 21.20 mg/kg diet, respectively. Collectively, Mn deficiency or excess could cause inflammation, apoptosis, antioxidant system disruption and change tight junction protein (claudin-b and claudin-15) transcription abundances, which might be partially related to the NF-κB p65, caspase-(3,8,9) and Nrf2 signaling, in the gills of fish.
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Affiliation(s)
- Wei-Dan Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Ren-Jun Tang
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Yang Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Pei Wu
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Sheng-Yao Kuang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Jun Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Ling Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Wu-Neng Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Yong-An Zhang
- Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Xiao-Qiu Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China.
| | - Lin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China.
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Xiong H, Tian L, Zhao Z, Chen S, Zhao Q, Hong J, Xie Y, Zhou N, Fu Y. The sinomenine enteric-coated microspheres suppressed the TLR/NF-κB signaling in DSS-induced experimental colitis. Int Immunopharmacol 2017; 50:251-262. [PMID: 28711031 DOI: 10.1016/j.intimp.2017.06.033] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Revised: 06/27/2017] [Accepted: 06/29/2017] [Indexed: 10/19/2022]
Abstract
Sinomenine is a pure alkaloid with immunosuppressive effects that is extracted from the Chinese medicinal plant Sinomenium acutum. We studied the therapeutic effects of sinomenine on inflammatory bowel disease. In this study, we randomly divided mice into the following ten groups: Control group; DSS-induced colitis group; Salicylazosulfapyridine (SASP)-treated group; Chitosan-treated group; low-, medium-, and high-dose sinomenine-treated and sinomenine enteric-coated microspheres-treated groups. We recorded changes in colon length, disease activity index (DAI), and colon pathology, measured TLR4, MyD88, SIGIRR, NF-κB p65 protein levels and inflammatory serum cytokine levels. Except for the Control group, the weight of mice in each group decreased, the DAI of the DSS-induced colitis group was significantly higher than the other groups, and the DAIs of the sinomenine- and sinomenine enteric-coated microspheres-treated groups were significantly lower than that of the SASP-treated group. TLR4, MyD88, NF-κB p65 and proinflammatory cytokine expressions decreased dose dependently in the sinomenine and sinomenine enteric-coated microspheres-treated groups and were generally lower in the sinomenine enteric-coated microspheres groups. However, SIGIRR and anti-inflammatory IL-10 expressions exhibited the opposite pattern. Based on the superior therapeutic effect, sinomenine enteric-coated microspheres might regulate TLR/NF-κB signaling and would be beneficial for an effective and safe therapy of inflammatory bowel disease.
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Affiliation(s)
- Huifang Xiong
- Department of Gastroenterology, the First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - Liang Tian
- Department of Pharmacy, Shanghai Neuromedical Center, Shanghai, China
| | - Zihan Zhao
- First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu Province, China
| | - Shuping Chen
- Department of Gastroenterology, the First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - Qiaoyun Zhao
- Department of Gastroenterology, the First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - Junbo Hong
- Department of Gastroenterology, the First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China
| | - Yong Xie
- Department of Gastroenterology, the First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, China.
| | - Nanjin Zhou
- Jiangxi Provincial Academy of Medical Science, Nanchang University, Nanchang, Jiangxi Province, China.
| | - Yingjun Fu
- School of Pharmacy, Nanchang University, Nanchang, Jiangxi Province, China
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Zhang CN, Zhang JL, Ren HT, Zhou BH, Wu QJ, Sun P. Effect of tributyltin on antioxidant ability and immune responses of zebrafish (Danio rerio). ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2017; 138:1-8. [PMID: 27987418 DOI: 10.1016/j.ecoenv.2016.12.016] [Citation(s) in RCA: 77] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Revised: 12/10/2016] [Accepted: 12/12/2016] [Indexed: 05/21/2023]
Abstract
Tributyltin (TBT) is a toxic compound released into aquatic ecosystems through antifouling paints. This study was designed to examine the effects of TBT on antioxidant ability and immune responses of zebrafish (Danio rerio). Three hundred sixty healthy zebrafish were randomly grouped into four groups and exposed to different doses of TBT (0, 1, 10 and 100ngL-1). At the end of 8 weeks, the fish were sampled, and antioxidant capability, immune parameters and immune-related genes were assessed. The results showed that with an increase in TBT dose, the concentration of malonaldehyde in the liver was significantly increased (p<0.05), whereas the activities of total superoxide dismutase, catalase and glutathione peroxidase were significantly decreased (p<0.05) compared to the control. The activity and expression of lysozyme and the content of immunoglobulin M were significantly decreased compared to those of the fish exposed to 0ngL-1 TBT (p<0.05). However, the expression of the HSP70, HSP90, tumor necrosis factor-α(TNF-α), interleukins (IL-1β, IL-6), and nuclear factor-kappa B p65 (NF-κ B p65) genes were all enhanced with an increase in TBT dose. The results indicated that TBT induced oxidative stress and had immunotoxic effects on zebrafish.
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Affiliation(s)
- Chun-Nuan Zhang
- College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang 471003, People's Republic of China.
| | - Ji-Liang Zhang
- College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang 471003, People's Republic of China
| | - Hong-Tao Ren
- College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang 471003, People's Republic of China
| | - Bian-Hua Zhou
- College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang 471003, People's Republic of China
| | - Qiu-Jue Wu
- College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang 471003, People's Republic of China
| | - Ping Sun
- College of Animal Science and Technology, Henan University of Scientific and Technology, Luoyang 471003, People's Republic of China
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Giri SS, Sen SS, Jun JW, Sukumaran V, Park SC. Role of Bacillus licheniformis VS16-Derived Biosurfactant in Mediating Immune Responses in Carp Rohu and its Application to the Food Industry. Front Microbiol 2017; 8:514. [PMID: 28400765 PMCID: PMC5368236 DOI: 10.3389/fmicb.2017.00514] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 03/13/2017] [Indexed: 01/31/2023] Open
Abstract
Multifarious applications of Bacillus licheniformis VS16-derived biosurfactant were explored. Labeo rohita fingerlings were injected intraperitoneally with 0.1 mL of phosphate-buffered saline (PBS) containing purified biosurfactant at 0 (control), 55 (S55), 110 (S110), 220 (S220), or 330 (S330) μg mL-1 concentrations. Various immunological parameters and the expression of immune-related genes were measured at 7, 14, and 21 days post-administration (dpa). At 21 dpa, fish were challenged with Aeromonas hydrophila and mortality was recorded for 14 days. Immune parameters such as lysozyme levels (39.29 ± 2.14 U mL-1), alternative complement pathway (61.21 ± 2.38 U mL-1), and phagocytic activities (33.37 ± 1.2%) were maximum (P < 0.05) in the S220 group at 14 dpa; but immunoglobulin levels (11.07 ± 0.83 mg mL-1) were highest in the S220 group at 7 dpa, compared to that in controls. Activities of digestive enzymes (amylase, protease, and lipase) were higher (P < 0.05) in the S220 and S330 groups than in the control group. Regarding cytokine gene expression, pro-inflammatory cytokines (TNF-α and IL-1β) were down-regulated (P < 0.05) in the S220 and S330 groups. Expression of IL-10, TGF-β, and IKB-α were up-regulated in the S220 and S330 groups at 14 dpa, with the highest levels in the S220 group. The expression of NF-κB p65 and IKK-β were down-regulated in treatment groups, and were lowest (P < 0.05) in the S220 group. The highest post-challenge survival rate (72.7%) was recorded in S220 group. Further, the potential of this substance to inhibit biofilm formation, and heavy metal removal from vegetables were also evaluated. Biosurfactant was effective in inhibiting biofilm formation up to 54.71 ± 1.27%. Moreover, it efficiently removed cadmium (Cd) from tested vegetables such as carrot, radish, ginger, and potato, with the highest removal efficiency (60.98 ± 1.29%) recorded in ginger contaminated with Cd. Collectively, these results suggest that isolated biosurfactant could be used in the aquaculture industry, in addition to its potential application to the food industry.
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Affiliation(s)
- Sib Sankar Giri
- Department of Biotechnology, Periyar Maniammai UniversityThanjavur, India; Laboratory of Aquatic Biomedicine, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National UniversitySeoul, South Korea
| | - Shib Sankar Sen
- School of Life Sciences, Jawaharlal Nehru University New Delhi, India
| | - Jin Woo Jun
- Laboratory of Aquatic Biomedicine, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University Seoul, South Korea
| | - V Sukumaran
- Department of Biotechnology, Periyar Maniammai University Thanjavur, India
| | - Se Chang Park
- Laboratory of Aquatic Biomedicine, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University Seoul, South Korea
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Xu HJ, Jiang WD, Feng L, Liu Y, Wu P, Jiang J, Kuang SY, Tang L, Tang WN, Zhang YA, Zhou XQ. Dietary vitamin C deficiency depressed the gill physical barriers and immune barriers referring to Nrf2, apoptosis, MLCK, NF-κB and TOR signaling in grass carp (Ctenopharyngodon idella) under infection of Flavobacterium columnare. FISH & SHELLFISH IMMUNOLOGY 2016; 58:177-192. [PMID: 27640333 DOI: 10.1016/j.fsi.2016.09.029] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2016] [Revised: 09/12/2016] [Accepted: 09/13/2016] [Indexed: 06/06/2023]
Abstract
This study explored the effects of vitamin C on the physical barriers and immune barriers, and relative mRNA levels of signaling molecules in the gill of grass carp (Ctenopharyngodon idella) under infection of Flavobacterium columnare. The results indicated that compared with optimal vitamin C supplementation, vitamin C deficiency (2.9 mg/kg diet) (1) increased reactive oxygen species, malondialdehyde and protein carbonyl (PC) contents (P < 0.05), decreased the copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities and mRNA levels (P < 0.05), and glutathione and vitamin C contents (P < 0.05), down-regulated NF-E2-related factor 2 mRNA level (P < 0.05), and up-regulated Kelch-like ECH-associating protein (Keap) 1a (rather than Keap1b) mRNA level (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency induced oxidative injury in fish gill; (2) up-regulated caspase-3, -7, -8, -9, Fas ligand, B-cell lymphoma protein 2 associated X protein, apoptotic protease activating factor-1 mRNA levels (P < 0.05), and down-regulated inhibitor of apoptosis protein and B-cell lymphoma-2 (rather than myeloid cell leukemia-1) mRNA level (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency aggravated cell apoptosis in fish gill; (3) up-regulated pore-forming TJs Claudin-12, 15a, -15b, and related signaling molecules myosin light chain kinase, p38 mitogen-activated protein kinase (rather than c-Jun N-terminal kinases) mRNA levels (P < 0.05), and down-regulated barrier-forming TJs Occludin, zonula occludens (ZO) 1, ZO-2, Claudin-c, -3c, -7a, -7b mRNA levels (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency disrupted tight junctional complexes in fish gill; (4) decreased lysozyme and acid phosphatase (ACP) activities, and complement 3 (C3), C4 and IgM contents (P < 0.05), down-regulated the mRNA levels of antimicrobial peptides liver expressed antimicrobial peptide (LEAP) 2A, LEAP-2B, Hepcidin, β-defensin mRNA levels (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency decrease fish gill immune function; (5) down-regulated the mRNA levels of anti-inflammatory cytokines-related factors interleukin 10 (IL-10), IL-11, transforming growth factor (TGF) β1, TGF-β2, inhibitor of κBa and eIF4E-binding protein 1 (4E-BP1) (rather than 4E-BP2) (P < 0.05), and up-regulated pro-inflammatory cytokines-related factors interferon γ2, IL-1β, IL-6, IL-8, IL-12 P35, IL-12 P40, nuclear factor κB (NF-κB) p65 (rather than NF-κB p52), IκB kinases (IKK) (only IKKα and IKKγ), target of rapamycin and ribosomal protein S6 kinase 1 mRNA levels (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency aggravated fish gill inflammation. In conclusion, vitamin C deficiency disrupted physical barriers and immune barriers, and regulated relative mRNA levels of signaling molecules in fish gill. The vitamin C requirement for against gill rot morbidity of grass carp (264-1031 g) was estimated to be 156.0 mg/kg diet. In addition, based on the gill biochemical indices (antioxidant indices MDA, PC and vitamin C contents, and immune indices LA and ACP activity) the vitamin C requirements for grass carp (264-1031 g) were estimated to be 116.8, 156.6, 110.8, 57.8 and 134.9 mg/kg diet, respectively.
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Affiliation(s)
- Hui-Jun Xu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China
| | - Wei-Dan Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, China
| | - Lin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, China
| | - Yang Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, China
| | - Pei Wu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, China
| | - Jun Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, China
| | - Sheng-Yao Kuang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Ling Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Wu-Neng Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Yong-An Zhang
- Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Xiao-Qiu Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, China.
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Liu S, Feng L, Jiang WD, Liu Y, Jiang J, Wu P, Zeng YY, Xu SD, Kuang SY, Tang L, Tang WN, Zhang YA, Zhou XQ. Impact of exogenous lipase supplementation on growth, intestinal function, mucosal immune and physical barrier, and related signaling molecules mRNA expression of young grass carp (Ctenopharyngodon idella). FISH & SHELLFISH IMMUNOLOGY 2016; 55:88-105. [PMID: 27164217 DOI: 10.1016/j.fsi.2016.05.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 04/30/2016] [Accepted: 05/04/2016] [Indexed: 06/05/2023]
Abstract
This study investigated the effects of exogenous lipase supplementation on the growth performance, intestinal growth and function, immune response and physical barrier function, and related signaling molecules mRNA expression of young grass carp (Ctenopharyngodon idella). A total of 450 grass carp (255.02 ± 0.34 g) were fed five diets for 60 days. There were 5 dietary treatments that included a normal protein and lipid diet containing 30% crude protein (CP) with 5% ether extract (EE), and the low-protein and high-lipid diets (28% CP, 6% EE) supplemented with graded levels of exogenous lipase supplementation activity at 0, 1193, 2560 and 3730 U/kg diet. The results indicated that compared with a normal protein and lipid diet (30% CP, 5% EE), a low-protein and high-lipid diet (28% CP, 6% EE) (un-supplemented lipase) improved lysozyme activities and complement component 3 contents in the distal intestine (DI), interleukin 10 mRNA expression in the proximal intestine (PI), and glutathione S-transferases activity and glutathione content in the intestine of young grass carp. In addition, in low-protein and high-lipid diets, optimal exogenous lipase supplementation significantly increased acid phosphatase (ACP) activities and complement component 3 (C3) contents (P < 0.05), up-regulated the relative mRNA levels of antimicrobial peptides (liver expressed antimicrobial peptide 2 and hepcidin) and anti-inflammatory cytokines (interleukin 10 and transforming growth factor β1) and signaling molecules inhibitor protein-κBα (IκBα) and target of rapamycin (TOR) (P < 0.05), down-regulated the mRNA levels of pro-inflammatory cytokines (tumor necrosis factor α, interleukin 8, interferon γ2, and interleukin 1β), and signaling molecules (nuclear factor kappa B p65, IκB kinase β, IκB kinase γ) (P < 0.05) in the intestine of young grass carp. Moreover, optimal exogenous lipase supplementation significantly decreased reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl (PC) contents (P < 0.05), improved the activities of anti-superoxide anion (ASA) and anti-hydroxyl radical (AHR), glutathione content, and the activities and mRNA levels of antioxidant enzymes (copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferases and glutathione reductase) (P < 0.05), up-regulated signaling molecule NF-E2-related factor 2 (Nrf2) (P < 0.05), down-regulated signaling molecules (Kelch-like-ECH-associated protein 1a, Kelch-like-ECH-associated protein 1b) (P < 0.05) in the intestine of young grass carp. Furthermore, optimal exogenous lipase supplementation significantly elevated the mRNA levels of tight junction proteins (Occludin, zonula occludens 1, Claudin b, Claudin c and Claudin 3) (P < 0.05), down-regulated the mRNA levels of tight junction proteins (Claudin 12 and Claudin 15a) (P < 0.05), down-regulated signaling molecules myosin light chain kinase (P < 0.05) in the intestine of young grass carp. In conclusion, dietary lipid could partially spare protein, and the low-protein and high-lipid diet could improve growth, intestinal growth and function, immune response and antioxidant capability of fish. Meanwhile, in high-fat and low-protein diets, optimal exogenous lipase supplementation improved growth, intestinal growth and function, intestinal immunity, physical barrier, and regulated the mRNA expression of related signal molecules of fish. The optimal level of exogenous lipase supplementation in young grass carp (255-771 g) was estimated to be 1193 U kg(-1) diet.
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Affiliation(s)
- Sen Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
| | - Lin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Wei-Dan Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Yang Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Jun Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Pei Wu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Yun-Yun Zeng
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Shu-De Xu
- Guangdong Vtr Bio-tech Co., Ltd., Zhuhai 519060, China
| | - Sheng-Yao Kuang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Ling Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Wu-Neng Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Yong-An Zhang
- Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
| | - Xiao-Qiu Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China.
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Gao W, Guo Y, Wang C, Lin Y, Yu L, Sheng T, Wu Z, Gong Y. Indirubin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice through the inhibition of inflammation and the induction of Foxp3-expressing regulatory T cells. Acta Histochem 2016; 118:606-614. [PMID: 27396532 DOI: 10.1016/j.acthis.2016.06.004] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 06/19/2016] [Accepted: 06/20/2016] [Indexed: 02/08/2023]
Abstract
Indirubin, an active ingredient of a traditional Chinese medicine prescription named Danggui Longhui Wan, has been reported to exhibit abroad anti-cancer and anti-inflammation activities. However, the effect of indirubin on ulcerative colitis (UC) has not been addressed. Here, we investigated the therapeutic efficacy of indirubin on dextran sulfate sodium (DSS)-induced UC in mice and explored its underlying mechanisms. UC model was induced in BALB/c mice by administrating with 3% DSS in drinking water for 7days. Subsequently, indirubin treatment (10mg/kg) for 7days obviously inhibited the loss of body weight, reversed the elevation of disease activity index (DAI), alleviated crypt distortion and mucosal injury, and reduced inflammatory cell infiltration in the colon mucosa, thereby ameliorating DSS-induced UC. Mechanically, the levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-2 as well as myeloperoxidase (MPO) activity in colon tissues were decreased significantly, while the levels of IL-4 and IL-10 were increased remarkably by indirubin treatment. Moreover, indirubin administration effectively suppressed CD4(+) T cell infiltration in the colon of DSS-induced UC mice and promoted the generation of Foxp3-expressing regulatory T cells. Additionally, further studies showed that indirubin obviously inhibited DSS-induced activation of nuclear factor (NF)-κB signaling. These results reveal that the significant anti-UC effect of indirubin may be attributable to its inhibition of inflammatory responses and promotion of Foxp3(+) T cells. Our studies provide the first evidence for the anti-UC effect of indirubin as well as the related molecular mechanisms and suggest a promising candidate drug for UC therapy.
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Giri SS, Sen SS, Jun JW, Sukumaran V, Park SC. Role of Bacillus subtilis VSG4-derived biosurfactant in mediating immune responses in Labeo rohita. FISH & SHELLFISH IMMUNOLOGY 2016; 54:220-229. [PMID: 27079425 DOI: 10.1016/j.fsi.2016.04.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2016] [Revised: 03/16/2016] [Accepted: 04/08/2016] [Indexed: 06/05/2023]
Abstract
This study aimed to isolate biosurfactant from CO2-sequestering Bacillus subtilis VSG4 and to evaluate its immunostimulatory effect in Labeo rohita fingerlings. Fish were injected intraperitoneally (i.p.) with 0.1 mL of phosphate-buffered saline (PBS) containing the water-soluble fraction of purified biosurfactant at 50 (S50), 100 (S100), 200 (S200), or 300 (S300) μg mL(-1). Fish injected with PBS served as controls. Various immunological parameters, including immune-related gene expression, were measured at 14, 21, and 28 days post administration (dpa). At 28 dpa, the fish were challenged with Aeromonas hydrophila and mortality was recorded up to 14 days. Among the immune parameters tested, lysozyme levels (36.32 ± 1.79 U mL(-1)), alternative complement pathway activity (76.26 ± 2.18 U mL(-1)), phagocytic activity (32.18 ± 0.67%), and serum bactericidal activity (73.2 ± 4.7%) were significantly higher (P < 0.05) in the S200 group at 21 dpa than in the controls. Respiratory burst activity (0.386 ± 0.008 OD630nm) was the highest in the S200 group at 28 dpa. Of the immune-related genes examined, pro-inflammatory cytokines (TNF-α and IL-1β) were significantly down-regulated in the S200 and S300 groups. Expression of anti-inflammatory cytokines (IL-10 and TGF-β) as well as IKB-α was higher (P < 0.05) in the S100‒S300 groups at 21 dpa. The expression of NF-κB p65, IKK-β, MAPKp38, and Myd88 was down-regulated in the treated groups when compared to the controls. Fish in the S200 group exhibited the highest post-challenge relative survival rate (67.88%). Collectively, these results suggest that secondary metabolite (biosurfactant) isolated from B. subtilis VSG4 at 200 μg mL(-1) can positively influence immune responses, enhance disease resistance, and stimulate immune-related gene expression in L. rohita.
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Affiliation(s)
- Sib Sankar Giri
- Laboratory of Aquatic Biomedicine, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, 151742, South Korea.
| | - Shib Sankar Sen
- School of Life Sciences, Jawharlal Nehru University, New Delhi, 110067, India.
| | - Jin Woo Jun
- Laboratory of Aquatic Biomedicine, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, 151742, South Korea.
| | - Venkatachalam Sukumaran
- Department of Biotechnology, Periyar Maniammai University, Thanjavur, 613403, Tamil Nadu, India.
| | - Se Chang Park
- Laboratory of Aquatic Biomedicine, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, 151742, South Korea.
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Zhang H, Gong C, Qu L, Ding X, Cao W, Chen H, Zhang B, Zhou G. Therapeutic effects of triptolide via the inhibition of IL-1β expression in a mouse model of ulcerative colitis. Exp Ther Med 2016; 12:1279-1286. [PMID: 27588050 PMCID: PMC4997980 DOI: 10.3892/etm.2016.3490] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Accepted: 03/29/2016] [Indexed: 12/13/2022] Open
Abstract
The present study aimed to investigate the effect of triptolide (TL) on ulcerative colitis (UC) and explore the potential association between the therapeutic effects of TL and IL-1β expression using a 4,4-dimethyl-4-silapentane-1-sulfonic acid (DSS)-induced mouse model to simulate human UC. A total of 70 BALB/c female mice were randomly allocated into seven equal groups: Group A, blank control; group B, normal saline injection; group C, propylene glycol injection; group D (TL1), 0.2 mg/kg TL; group E (TL2), 0.4 mg/kg TL; group F (TL3), 0.6 mg/kg TL; and group G, dexamethasone injection. Mice activity, diet and stool characteristics were recorded daily. Mice were sacrificed by cervical dislocation on day 8, and disease activity indices, colon tissue histological scores and colonic histopathological scores were subsequently calculated. Serum levels of IL-1β were evaluated by enzyme-linked immunosorbent assay, and IL-1β expression levels were examined by reverse transcription-quantitative polymerase chain reaction with colonic mucosa specimen at the gene level and western blot analysis at the protein level. The IL-1β mRNA and protein expression levels were significantly elevated in the normal saline injection and propylene glycol injection groups compared with the blank control group and (P<0.01). In TL (TL2 and TL3)- and dexamethasone-treated mice, IL-1β expression levels were significantly decreased, as compared with the normal saline and propylene glycol injection groups (P<0.05). No significant difference was detected between TL (TL2 and TL3) and dexamethasone treatments. The results of the present study indicated that IL-1β expression was upregulated in the UC mouse model, which may be associated with the development and progression of UC. Furthermore, TL inhibited IL-1β expression, suggesting that TL may be a novel therapeutic target for the treatment of UC.
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Affiliation(s)
- Haifeng Zhang
- Department of Infectious Diseases, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Chen Gong
- Department of Gastroenterology, The First People's Hospital of Taicang, Taicang, Jiangsu 215401, P.R. China
| | - Lishuai Qu
- Department of Gastroenterology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Xiaoling Ding
- Department of Gastroenterology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Wei Cao
- Department of Gastroenterology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Haiqin Chen
- Department of Gastroenterology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Bin Zhang
- Department of Infectious Diseases, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Guoxiong Zhou
- Department of Gastroenterology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
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Feng L, Chen YP, Jiang WD, Liu Y, Jiang J, Wu P, Zhao J, Kuang SY, Tang L, Tang WN, Zhang YA, Zhou XQ. Modulation of immune response, physical barrier and related signaling factors in the gills of juvenile grass carp (Ctenopharyngodon idella) fed supplemented diet with phospholipids. FISH & SHELLFISH IMMUNOLOGY 2016; 48:79-93. [PMID: 26584756 DOI: 10.1016/j.fsi.2015.11.020] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 10/27/2015] [Accepted: 11/10/2015] [Indexed: 06/05/2023]
Abstract
This study was conducted to investigate the effects of dietary phospholipids (PL) on the gill immune response and physical barrier of juvenile grass carp (Ctenopharyngodon idella). A total of 1080 juvenile grass carp with an average initial weight of 9.34 ± 0.03 g were fed six semi-purified diets containing 0.40% (unsupplemented control group), 1.43%, 2.38%, 3.29%, 4.37% and 5.42% PL for 2 months. Compared with the control group, optimal PL supplementation increased (P < 0.05): (1) the lysozyme activity, acid phosphatase activity, complement component 3 (C3) content, liver expressed antimicrobial peptide 1 (LEAP-1) and LEAP-2 mRNA expression; (2) the relative mRNA expression of interleukin 10, transforming growth factor β1, inhibitor factor κBα (IκBα) and target of rapamycin (TOR); (3) the activities of anti-superoxide anion (ASA), anti-hydroxyl radical (AHR), copper/zinc superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), glutathione content and mRNA levels of SOD1, CAT, GPx, GR and NF-E2-related factor 2 (Nrf2) genes; (4) the transcription abundance of occludin, claudin b, claudin c, claudin 12 and zonula occludens 1 genes. At the same time, appropriate PL supplementation decreased (P < 0.05): (1) tumor necrosis factor α, interleukin 1β, nuclear factor κB p65 (NF-κB p65), IκB kinase β (IKKβ) and IκB kinase γ (IKKγ) mRNA expression; (2) malondialdehyde (MDA), protein carbonyl (PC) and reactive oxygen species (ROS) content and the relative mRNA expression of Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b; (3) the transcription abundance of myosin light chain kinase (MLCK) and p38 mitogen-activated protein kinase (p38 MAPK) genes. In conclusion, the positive effect of PL on gill health is associated with the improvement of the immunity, antioxidant status and tight junction barrier of fish gills. Finally, based on ACP activity, C3 content, PC content and ASA activity in the gills, the optimal dietary PL level for juvenile grass carp (9.34-87.50 g) was estimated to be 3.62%, 4.30%, 3.91% and 3.86%, respectively.
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Affiliation(s)
- Lin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Yong-Po Chen
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Wei-Dan Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Yang Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Jun Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Pei Wu
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Juan Zhao
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Sheng-Yao Kuang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Ling Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Wu-Neng Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Yong-An Zhang
- Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Xiao-Qiu Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China.
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Chen L, Feng L, Jiang WD, Jiang J, Wu P, Zhao J, Kuang SY, Tang L, Tang WN, Zhang YA, Zhou XQ, Liu Y. Intestinal immune function, antioxidant status and tight junction proteins mRNA expression in young grass carp (Ctenopharyngodon idella) fed riboflavin deficient diet. FISH & SHELLFISH IMMUNOLOGY 2015; 47:470-484. [PMID: 26419312 DOI: 10.1016/j.fsi.2015.09.037] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Revised: 09/14/2015] [Accepted: 09/24/2015] [Indexed: 06/05/2023]
Abstract
This study investigated the effects of riboflavin on intestinal immunity, tight junctions and antioxidant status of young grass carp (Ctenopharyngodon idella). Fish were fed diets containing graded levels of riboflavin (0.63-10.04 mg/kg diet) for 8 weeks. The study indicated that riboflavin deficiency decreased lysozyme, acid phosphatase, copper/zinc superoxide dismutase, glutathione reductase and glutathione peroxidase activities, and contents of complement component 3 and reduced glutathione in the intestine of fish (P < 0.05). Meanwhile, riboflavin deficiency increased reactive oxygen species, malondialdehyde and protein carbonyl contents and catalase activity (P < 0.05) in the intestine of fish. Furthermore, real-time polymerase chain reaction analysis was used to investigate mRNA expression patterns and found that the mRNA levels of interleukin 10 and transforming growth factor β1, Occludin, zonula occludens 1, Claudin-b and Claudin-c, inhibitor protein κBα, target of rapamycin, ribosomal S6 protein kinase 1 and NF-E2-related factor 2, copper/zinc superoxide dismutase, glutathione peroxidase and glutathione reductase were decreased (P < 0.05) in the intestine of fish fed riboflavin-deficient diet. Conversely, the mRNA levels of tumor necrosis factor α, interleukin 1β, interleukin 8, nuclear factor kappa B p65, Ikappa B kinase β, Ikappa B kinase γ, Kelch-like-ECH-associated protein 1b, p38 mitogen-activated protein kinase, myosin light chain kinase and Claudin-12 were increased (P < 0.05) in the intestine of fish fed riboflavin-deficient diet. In conclusion, riboflavin deficiency decreased immunity and structural integrity of fish intestine. The optimum riboflavin level for intestinal acid phosphatase activity of young grass carp was estimated to be 6.65 mg/kg diet.
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Affiliation(s)
- Liang Chen
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
| | - Lin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Wei-Dan Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Jun Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Pei Wu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Juan Zhao
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
| | - Sheng-Yao Kuang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Ling Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Wu-Neng Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Yong-An Zhang
- Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
| | - Xiao-Qiu Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China.
| | - Yang Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China.
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Chen YP, Jiang WD, Liu Y, Jiang J, Wu P, Zhao J, Kuang SY, Tang L, Tang WN, Zhang YA, Zhou XQ, Feng L. Exogenous phospholipids supplementation improves growth and modulates immune response and physical barrier referring to NF-κB, TOR, MLCK and Nrf2 signaling factors in the intestine of juvenile grass carp (Ctenopharyngodon idella). FISH & SHELLFISH IMMUNOLOGY 2015; 47:46-62. [PMID: 26306855 DOI: 10.1016/j.fsi.2015.08.024] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2015] [Revised: 06/29/2015] [Accepted: 08/21/2015] [Indexed: 06/04/2023]
Abstract
This study was conducted to investigate the effects of dietary phospholipids (PL) on the growth performance, intestinal enzyme activity and immune response and intestinal physical barrier of juvenile grass carp (Ctenopharyngodon idella). A total of 1080 juvenile grass carp with an average initial weight of 9.34 ± 0.03 g were fed six semi-purified diets containing 0.40% (unsupplemented control group), 1.43%, 2.38%, 3.29%, 4.37% and 5.42% PL for 2 months. Results indicated that 3.29% PL increased lysozyme (LZ) and acid phosphatase (ACP) activities and complement component 3 (C3) content (P < 0.05), up-regulated the mRNA relative expression levels of interleukin 10, transforming growth factor β1 (TGF-β1), inhibitor protein κBα (IκBα), target of rapamycin (TOR) and casein kinase 2 (CK2) (P < 0.05), and down-regulated tumor necrosis factor α (TNF-α), interleukin 1β, nuclear factor κB p65 (NF-κB p65), IκB kinase β (IKKβ) and IκB kinase γ (IKKγ) mRNA relative expression levels (P < 0.05) in the intestine, suggesting that optimum PL could improve fish intestinal immunity. In addition, 3.29% PL increased the activities of anti-superoxide anion (ASA), anti-hydroxyl radical, copper/zinc superoxide dismutase (SOD1), glutathione peroxidase (GPx) and glutathione reductase (GR), the content of glutathione (P < 0.05), and the mRNA relative expression levels of occludin, zonula occludens 1 (ZO-1), claudin 3, claudin 12, claudin b, claudin c, SOD1, GPx, GR and NF-E2-related factor 2 (Nrf2) and decreased malondialdehyde (MDA), protein carbonyl (PC) and ROS content (P < 0.05), the mRNA relative expression levels of Kelch-like-ECH-associated protein 1a (Keap1a), myosin light chain kinase (MLCK) and p38 mitogen-activated protein kinase (p38 MAPK) in the intestine, indicating that the optimum PL could improve fish intestinal physical barrier. Finally, based on the PWG, C3 content in the DI, ACP activity in the DI, intestinal PC content and intestinal ASA activity, the optimal dietary PL levels for juvenile grass carp (9.34-87.50 g) were estimated to be 3.46%, 3.79%, 3.93%, 3.72%, and 4.12%, respectively.
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Affiliation(s)
- Yong-Po Chen
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu 611130, China
| | - Wei-Dan Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu 611130, China
| | - Yang Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu 611130, China
| | - Jun Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu 611130, China
| | - Pei Wu
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu 611130, China
| | - Juan Zhao
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu 611130, China
| | - Sheng-Yao Kuang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Ling Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Wu-Neng Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Yong-An Zhang
- Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
| | - Xiao-Qiu Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu 611130, China.
| | - Lin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Sichuan, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu 611130, China.
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Arya A, Pathak DP, Majumdar DK, Manchanda S. Methacrylic acid-co-butylmethacrylate copolymers: design, characterization and evaluation as encapsulating material for colon targeted formulations. Des Monomers Polym 2015. [DOI: 10.1080/15685551.2015.1092011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Jiang WD, Wen HL, Liu Y, Jiang J, Kuang SY, Wu P, Zhao J, Tang L, Tang WN, Zhang YA, Zhou XQ, Feng L. The tight junction protein transcript abundance changes and oxidative damage by tryptophan deficiency or excess are related to the modulation of the signalling molecules, NF-κB p65, TOR, caspase-(3,8,9) and Nrf2 mRNA levels, in the gill of young grass carp (Ctenopharyngodon idellus). FISH & SHELLFISH IMMUNOLOGY 2015; 46:168-180. [PMID: 26057461 DOI: 10.1016/j.fsi.2015.06.002] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Revised: 06/01/2015] [Accepted: 06/02/2015] [Indexed: 06/04/2023]
Abstract
This study is for the first time to explore the possible effects of dietary tryptophan (Trp) on structural integrity and the related signalling factor gene expression in the gill of young grass carp (Ctenopharyngodon idella). Fish were fed with six different experimental diets containing graded levels of Trp at 0.7 (control), 1.7, 3.1, 4.0, 5.2 and 6.1 g kg(-1) diet for 8 weeks. The results firstly demonstrated that Trp deficiency or excess caused increases in reactive oxygen species (ROS) contents, and severe oxidative damage (lipid peroxidation and protein oxidation) in the gill of fish, and those negative effects could be reversed by optimal Trp levels. Secondly, compared with the optimal Trp levels, Trp deficiency could cause decreases in the mRNA levels of the barrier functional proteins (occludin, zonula occludens-1, claudin-c, and -3) and increases in the mRNA levels of the pore-formation proteins (claudin-12 and -15) mRNA levels in the gill of fish, and those were reversed by the optimal levels of Trp. The negative effects of Trp deficiency on those tight junction protein gene expression might be partly related to the increases in the mRNA levels of pro-inflammatory cytokines and related signalling factors (tumor necrosis factor α, interleukin 8, interleukin 1β and transcription factor-κB) and decreases in the mRNA levels of anti-inflammatory cytokines and related signalling factors [interleukin 10, transforming growth factor-β1, nuclear inhibitor factor κBα (iκBα), target of rapamyc and ribosome protein S6 kinase 1 (S6K1)] in the gill of fish. In addition, optimal dietary Trp protected the gill of fish against its deficiency-caused increases in the mRNA levels of the apoptosis signalling (caspase-3, caspase-8, caspase-9) and decreases in anti-superoxide radicals capacity, anti-hydroxyl radical capacity, glutathione contents and the activities of Cu/Zn superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) in the gill of fish. Additionally, compared with the Trp deficiency, optimal Trp up-regulated the mRNA levels of SOD, CAT, GPx, GR and GST, which might be partly ascribed to the up-regulation of the NF-E2-related factor 2 (Nrf2) mRNA levels and the down-regulation of Kelch-like-ECH-associated protein 1 (Keap1) mRNA levels in the gill of fish. Interestingly, excessive Trp caused similar results with its deficiency. Collectively, Trp deficiency or excess could cause antioxidant system disruption and change tight junction protein transcription abundances, which were partly related to the signalling factors, NF-κB p65, TOR, caspase-(3,8,9) and Nrf2, in fish gill, those could be blocked by the optimal Trp levels.
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Affiliation(s)
- Wei-Dan Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Hai-Lang Wen
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Yang Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Jun Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Sheng-Yao Kuang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Pei Wu
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Juan Zhao
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China
| | - Ling Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Wu-Neng Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Yong-An Zhang
- Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Xiao-Qiu Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China.
| | - Lin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Fish Nutrition and Safety in Production Sichuan University Key Laboratory, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Sichuan, Chengdu, 611130, China.
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Wang Y, Mao G, Lv Y, Huang Q, Wang G. MicroRNA-181b stimulates inflammation via the nuclear factor-κB signaling pathway in vitro. Exp Ther Med 2015; 10:1584-1590. [PMID: 26622531 DOI: 10.3892/etm.2015.2702] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2014] [Accepted: 07/29/2015] [Indexed: 01/11/2023] Open
Abstract
Acute lung injury (ALI) is characterized by severe lung edema and an increase in the inflammatory reaction. Considerable evidence has indicated that microRNAs (miRNAs or miRs) are involved in various human diseases; however, the expression profile and function of miRNAs in ALI have been rarely reported. The present study used miRNA microarray and reverse transcription-quantitative polymerase chain reaction to demonstrate that miR-181b is the one of the most significantly upregulated miRNA after lipopolysaccharide (LPS) stimulation in human bronchial epithelial cells, BEAS-2B. To elaborate the role of miR-181b in ALI, an assay was performed to investigate the overexpression of miR-181b in BEAS-2B cells, and the expression of inflammatory factors was then analyzed. The overexpression of miR-181b resulted in the induction of an increment in interleukin (IL)-6 levels. p65 was identified to be a primary component of NF-κB, since it was upregulated in the miR-181b overexpression in the BEAS-2B cells, while pyrrolidine dithiocarbamate, a specific inhibitor of NF-κB, was found to be able to abrogate the upregulation of the expression of p65. In conclusion, the findings of the present study suggested that miR-181b may be involved in the process of LPS-induced inflammation in BEAS-2B cells by activating the NF-κB signaling pathway, which implies that it may serve as a potential therapeutic target for ALI.
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Affiliation(s)
- Yazhen Wang
- Zhejiang Provincial Key Laboratory of Geriatrics and Geriatrics Institute of Zhejiang, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
| | - Genxiang Mao
- Zhejiang Provincial Key Laboratory of Geriatrics and Geriatrics Institute of Zhejiang, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
| | - Yuandong Lv
- Zhejiang Provincial Key Laboratory of Geriatrics and Geriatrics Institute of Zhejiang, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
| | - Qingdong Huang
- Zhejiang Provincial Key Laboratory of Geriatrics and Geriatrics Institute of Zhejiang, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
| | - Guofu Wang
- Zhejiang Provincial Key Laboratory of Geriatrics and Geriatrics Institute of Zhejiang, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China
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Chen L, Feng L, Jiang WD, Jiang J, Wu P, Zhao J, Kuang SY, Tang L, Tang WN, Zhang YA, Zhou XQ, Liu Y. Dietary riboflavin deficiency decreases immunity and antioxidant capacity, and changes tight junction proteins and related signaling molecules mRNA expression in the gills of young grass carp (Ctenopharyngodon idella). FISH & SHELLFISH IMMUNOLOGY 2015; 45:307-320. [PMID: 25882633 DOI: 10.1016/j.fsi.2015.04.004] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Revised: 03/31/2015] [Accepted: 04/04/2015] [Indexed: 06/04/2023]
Abstract
This study investigated the effects of dietary riboflavin on the growth, gill immunity, tight junction proteins, antioxidant system and related signaling molecules mRNA expression of young grass carp (Ctenopharyngodon idella). Fish were fed six diets containing graded levels of riboflavin (0.63-10.04 mg/kg diet) for 8 weeks. The study indicated that riboflavin deficiency decreased lysozyme and acid phosphatase activities, and complement component 3 content in the gills of fish (P < 0.05). Moreover, riboflavin deficiency caused oxidative damage, which might be partly due to decrease copper, zinc superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and glutathione-S-transferase activities and reduced glutathione content in the gills of fish (P < 0.05). Furthermore, the relative mRNA levels of antimicrobial peptides (liver expressed antimicrobial peptide 2 and Hepcidin), anti-inflammatory cytokines (interleukin 10 and transforming growth factor β1), tight junction proteins (Occludin, zonula occludens 1, Claudin-c and Claudin-3), signaling molecules (inhibitor of κBα, target of rapamycin and NF-E2-related factor 2) and antioxidant enzymes (copper, zinc superoxide dismutase and glutathione reductase) were significantly decreased (P < 0.05) in the gills of fish fed riboflavin-deficient diet. Conversely, the mRNA levels of pro-inflammatory cytokines (tumor necrosis factor α, interleukin 8, interferon γ2, and interleukin 1β), signaling molecules (nuclear factor kappa B p65, IκB kinase β, IκB kinase γ, Kelch-like-ECH-associated protein 1b and myosin light chain kinase) and tight junction protein Claudin-12 were significantly increased (P < 0.05) in the gills of fish fed riboflavin-deficient diet. In addition, this study indicated for the first time that young fish fed a riboflavin-deficient diet exhibited anorexia and poor growth. In conclusion, riboflavin deficiency decreased growth and gill immunity, impaired gill antioxidant system, as well as regulated mRNA expression of gill tight junction proteins and related signaling molecules of fish. Based on percent weight gain, gill lysozyme activity and reduced glutathione content, the dietary riboflavin requirements for young grass carp (275-722 g) were estimated to be 5.85, 7.39 and 6.34 mg/kg diet, respectively.
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Affiliation(s)
- Liang Chen
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
| | - Lin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Wei-Dan Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Jun Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Pei Wu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Juan Zhao
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
| | - Sheng-Yao Kuang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Ling Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Wu-Neng Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Yong-An Zhang
- Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
| | - Xiao-Qiu Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China.
| | - Yang Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China.
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Feng L, Luo JB, Jiang WD, Liu Y, Wu P, Jiang J, Kuang SY, Tang L, Zhang YA, Zhou XQ. Changes in barrier health status of the gill for grass carp (Ctenopharyngodon idella) during valine deficiency: Regulation of tight junction protein transcript, antioxidant status and apoptosis-related gene expression. FISH & SHELLFISH IMMUNOLOGY 2015; 45:239-249. [PMID: 25917968 DOI: 10.1016/j.fsi.2015.04.023] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Revised: 04/16/2015] [Accepted: 04/18/2015] [Indexed: 06/04/2023]
Abstract
This study investigated the effects of dietary valine on tight junction protein transcription, antioxidant status and apoptosis on grass carp gills (Ctenopharyngodon idella). Fish were fed six different experimental diets containing graded levels of valine (4.3, 8.0, 10.6, 13.1, 16.7, 19.1 g/kg). The results indicated that valine deficiency decreased Claudin b, Claudin 3, Occludin and ZO-1 transcription and increased Claudin 15 expression in the fish gill (P < 0.05). These effects were partly due to the down-regulation of interleukin 10 (IL-10), transforming growth factor β1 (TGF-β1) and IκB α and the up-regulation of relative mRNA expression of interleukin 1β (IL-1β), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α) and nuclear factor κB P65 (NF-κB P65) (P < 0.05). However, valine deficiency and valine supplementation did not have a significant effect on Claudin c and Claudin 12 expression in grass carp gills (P > 0.05). Valine deficiency also disrupted antioxidant status in the gill by decreasing anti-superoxide radicals and hydroxyl radical capacity, glutathione contents and the activities and mRNA levels of Cu/Zn superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) (P < 0.05). These results may be ascribed to the down-regulation of NF-E2-related factor 2 (Nrf2), target of rapamycin (TOR) and ribosomal protein S6 kinase 1 (S6K1) and the up-regulation of Kelch-like-ECH-associated protein 1 (Keap1) (P < 0.05). Additionally, valine deficiency induced DNA fragmentation via the up-regulation of Caspase 3, Caspase 8 and Caspase 9 expressions (P < 0.05). These results may be ascribed to the improvement in ROS levels in the fish gill (P < 0.05). Taken together, the results showed that valine deficiency impaired the structural integrity of fish gill by disrupted fish antioxidant defenses and regulating the expression of tight junction protein, cytokines, antioxidant enzymes, NF-κB p65, IκBα, TOR, Nrf2, Keap1 and apoptosis-related genes in the fish gill.
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Affiliation(s)
- Lin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, China
| | - Jian-Bo Luo
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China
| | - Wei-Dan Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, China
| | - Yang Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, China
| | - Pei Wu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, China
| | - Jun Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, China
| | - Sheng-Yao Kuang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Ling Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, China
| | - Yong-An Zhang
- Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
| | - Xiao-Qiu Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, China.
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Marzaro G, Lampronti I, Borgatti M, Manzini P, Gambari R, Chilin A. Psoralen derivatives as inhibitors of NF-κB interaction: the critical role of the furan ring. Mol Divers 2015; 19:551-61. [PMID: 25869956 DOI: 10.1007/s11030-015-9586-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Accepted: 03/21/2015] [Indexed: 12/26/2022]
Abstract
Simplified analogues of previously reported NF-κB interaction inhibitors, lacking the furan moiety, were synthesized and evaluated by performing experiments based on electrophoretic mobility shift assay (EMSA). The synthetic modifications led to simpler coumarin derivatives with lower activity allowing to better understand the minimal structural requirement for the binding to NF-κB.
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Affiliation(s)
- Giovanni Marzaro
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131, Padova, Italy
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Zhang ZL, Fan HY, Yang MY, Zhang ZK, Liu K. Therapeutic effect of a hydroxynaphthoquinone fraction on dextran sulfate sodium-induced ulcerative colitis. World J Gastroenterol 2014; 20:15310-15318. [PMID: 25386079 PMCID: PMC4223264 DOI: 10.3748/wjg.v20.i41.15310] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Revised: 06/21/2014] [Accepted: 07/16/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the therapeutic effect of hydroxynaphthoquinone mixture (HM) on dextran sulfate sodium (DSS)-induced colitis and explore the underlying mechanisms.
METHODS: BALB/c mice received 3.5% DSS for 6 d to induce ulcerative colitis. Groups of mice were orally administered HM 3.5, 7 and 14 mg/kg and mesalazine 200 mg/kg per day for 7 d. During the experiment, clinical signs and body weight, stool consistency and visible fecal blood were monitored and recorded daily. A disease activity index score was calculated for each animal. At the conclusion of the experiment, the colonic histopathological lesions were evaluated. Myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) levels were determined. Protein expression levels of TNF-α, nuclear factor-κB (NF-κB) p65, inhibitor of κB (IκB) and phosphorylation of IκB (p-IκB) were analyzed by Western blot analysis.
RESULTS: Administration of 3.5% DSS for 6 d successfully induced acute colitis associated with soft stool, diarrhea, rectal bleeding, and colon shortening, as well as a loss of body weight. Administration of HM effectively attenuated the severity of colonic mucosa injury. For histopathological analysis, HM treatment improved histological alterations and lowered pathological scores compared with the DSS only group. This manifested as a reduction in the extent of colon injury and inflammatory cell infiltration, as well as the degree of mucosal destruction. In addition, HM at doses of 7 and 14 mg/kg significantly decreased MPO activity in colonic tissue (0.98 ± 0.22 U/g vs 1.32 ± 0.24 U/g, 0.89 ± 0.37 U/g vs 1.32 ± 0.24 U/g tissue, P < 0.05) and serum TNF-α levels (68.78 ± 7.34 ng/L vs 88.98 ± 17.79 ng/L, 64.13 ± 14.13 ng/L vs 88.98 ± 17.79 ng/L, P < 0.05). Furthermore, HM down-regulated the expression of TNF-α, NF-κB p65 and p-IκBα in colonic tissue while up-regulating IκBα protein expression. These results suggest that the significant anti-inflammatory effect of HM may be attributable to its inhibition of TNF-α production and NF-κB activation.
CONCLUSION: HM had a favorable therapeutic effect on DSS-induced ulcerative colitis, supporting its further development and clinical application in inflammatory bowel disease.
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The anti-inflammation effect of baicalin on experimental colitis through inhibiting TLR4/NF-κB pathway activation. Int Immunopharmacol 2014; 23:294-303. [PMID: 25239813 DOI: 10.1016/j.intimp.2014.09.005] [Citation(s) in RCA: 157] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2014] [Revised: 08/19/2014] [Accepted: 09/05/2014] [Indexed: 12/25/2022]
Abstract
BACKGROUND Baicalin holds a protective effect on inflammatory responses in several diseases. However, its molecular mechanism of anti-inflammatory activity on ulcerative colitis (UC) remains unknown. The present study was conducted to verify whether the anti-inflammation effect of baicalin on experimental colitis is via inhibiting TLR4/NF-κB pathway activation. METHODS The inflammatory response in RAW264.7 cells was induced by LPS and in rats by intrarectal administration of TNBS. Western blot analysis was carried out to examine toll-like receptor 4 (TLR4), NF-κB, p-NF-κB p65, IκB and p-IκB protein expressions in cells. Furthermore, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), cyclo-oxygenase-2 (Cox-2), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 levels in cell supernatant and rat serum were detected by appropriate kits. An immunohistochemical assay was applied to examine TNF-α and IL-1β protein expression in colon tissues and TLR4 and p-NF-κB p65 protein expressions in RAW264.7 cells. RESULTS Baicalin ameliorates the considered inflammatory symptoms of induced colitis. It could also down-regulate pro-inflammatory mediators in the colon mucosa. The decline in the production of pro-inflammatory cytokines was correlated with the decrease in mucosal TLR4 protein expression. The expression of p-NF-κB p65 protein was significantly decreased, which correlated with a similar decrease in p-IκB protein. Consistent with the in vivo results, baicalin blocked LPS-stimulated nuclear translocation of p-NF-κB p65 in mouse macrophage RAW264.7 cells. CONCLUSIONS The present study indicates for the first time that the mechanism for baicalin on abrogating experimental colitis was targeted inhibition of the TLR4/NF-κB pathway activation.
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Dou W, Zhang J, Ren G, Ding L, Sun A, Deng C, Wu X, Wei X, Mani S, Wang Z. Mangiferin attenuates the symptoms of dextran sulfate sodium-induced colitis in mice via NF-κB and MAPK signaling inactivation. Int Immunopharmacol 2014; 23:170-8. [PMID: 25194678 DOI: 10.1016/j.intimp.2014.08.025] [Citation(s) in RCA: 108] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2014] [Revised: 08/06/2014] [Accepted: 08/26/2014] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal (GI) tract, and currently no curative treatment is available. Mangiferin, a natural glucosylxanthone mainly from the fruit, leaves and stem bark of a mango tree, has a strong anti-inflammatory activity. We sought to investigate whether mangiferin attenuates inflammation in a mouse model of chemically induced IBD. Pre-administration of mangiferin significantly attenuated dextran sulfate sodium (DSS)-induced body weight loss, diarrhea, colon shortening and histological injury, which correlated with the decline in the activity of myeloperoxidase (MPO) and the level of tumor necrosis factor-α (TNF-α) in the colon. DSS-induced degradation of inhibitory κBα (IκBα) and the phosphorylation of nuclear factor-kappa B (NF-κB) p65 as well as the mRNA expression of pro-inflammatory mediators (inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), TNF-α, interleukin-1β (IL-1β) and IL-6) in the colon were also downregulated by mangiferin treatment. Additionally, the phosphorylation/activation of DSS-induced mitogen-activated protein kinase (MAPK) proteins was also inhibited by mangiferin treatment. In accordance with the in vivo results, mangiferin exposure blocked TNF-α-stimulated nuclear translocation of NF-κB in RAW264.7 mouse macrophage cells. Transient transfection gene reporter assay performed in TNF-α-stimulated HT-29 human colorectal adenocarcinoma cells indicated that mangiferin inhibits NF-κB transcriptional activity in a dose-dependent manner. The current study clearly demonstrates a protective role for mangiferin in experimental IBD through NF-κB and MAPK signaling inhibition. Since mangiferin is a natural compound with little toxicity, the results may contribute to the effective utilization of mangiferin in the treatment of human IBD.
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Affiliation(s)
- Wei Dou
- Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Jingjing Zhang
- Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Gaiyan Ren
- Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Lili Ding
- Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Aning Sun
- Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Chao Deng
- Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xiaojun Wu
- Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xiaohui Wei
- Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Sridhar Mani
- Department of Medicine, Albert Einstein College of Medicine, NY 10461, USA
| | - Zhengtao Wang
- Shanghai Key Laboratory of Formulated Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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Luo JB, Feng L, Jiang WD, Liu Y, Wu P, Jiang J, Kuang SY, Tang L, Zhang YA, Zhou XQ. The impaired intestinal mucosal immune system by valine deficiency for young grass carp (Ctenopharyngodon idella) is associated with decreasing immune status and regulating tight junction proteins transcript abundance in the intestine. FISH & SHELLFISH IMMUNOLOGY 2014; 40:197-207. [PMID: 25014314 DOI: 10.1016/j.fsi.2014.07.003] [Citation(s) in RCA: 104] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2014] [Revised: 07/02/2014] [Accepted: 07/02/2014] [Indexed: 06/03/2023]
Abstract
This study investigated the effects of dietary valine on the growth, intestinal immune response, tight junction proteins transcript abundance and gene expression of immune-related signaling molecules in the intestine of young grass carp (Ctenopharyngodon idella). Six iso-nitrogenous diets containing graded levels of valine (4.3-19.1 g kg(-)(1) diet) were fed to the fish for 8 weeks. The results showed that percentage weight gain (PWG), feed intake and feed efficiency of fish were the lowest in fish fed the valine-deficient diet (P < 0.05). In addition, valine deficiency decreased lysozyme, acid phosphatase activities and complement 3 content in the intestine (P < 0.05), down-regulated mRNA levels of interleukin 10, transforming growth factor β1, IκBα and target of rapamycin (TOR) (P < 0.05), and up-regulated tumor necrosis factor α, interleukin 8 and nuclear factor κB P65 (NF-κB P65) gene expression (P < 0.05). Additionally, valine deficiency significantly decreased transcript of Occludin, Claudin b, Claudin c, Claudin 3, and ZO-1 (P < 0.05), and improved Claudin 15 expression in the fish intestine (P < 0.05). However, valine did not have a significant effect on expression of Claudin 12 in the intestine of grass carp (P > 0.05). In conclusion, valine deficiency decreased fish growth and intestinal immune status, as well as regulated gene expression of tight junction proteins, NF-κB P65, IκBα and TOR in the fish intestine. Based on the quadratic regression analysis of lysozyme activity or PWG, the dietary valine requirement of young grass carp (268-679 g) were established to be 14.47 g kg(-1) diet (4.82 g 100 g(-1) CP) or 14.00 g kg(-1) diet (4.77 g 100 g(-1) CP), respectively.
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Affiliation(s)
- Jian-Bo Luo
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
| | - Lin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China.
| | - Wei-Dan Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Yang Liu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Pei Wu
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Jun Jiang
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Sheng-Yao Kuang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Ling Tang
- Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu 610066, China
| | - Yong-An Zhang
- Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
| | - Xiao-Qiu Zhou
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China.
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