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Wang Z, Xie J, Wang G, Yang H, Li Z, Zhang K, Shu R, Xie W, Tian J, Li H, Gong W, Xia Y. Enhanced gut damage and microbial imbalance in bullfrog tadpoles (Lithobates catesbeiana) exposed to polystyrene microplastics under high-temperature conditions. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2025; 375:126339. [PMID: 40318781 DOI: 10.1016/j.envpol.2025.126339] [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: 01/07/2025] [Revised: 04/21/2025] [Accepted: 04/28/2025] [Indexed: 05/07/2025]
Abstract
The potential threat posed by microplastic pollution to ecosystems has garnered widespread attention. Additionally, the combined effects of climate warming and environmental pollutants may further exacerbate the negative impacts on aquatic organisms. In this study, the effects of polystyrene microplastics (PS-MPs) on the oxidative stress status, inflammatory response, and gut microbiota composition of bullfrog tadpoles (Lithobates catesbeiana) were systematically evaluated under different temperatures. Histological analysis, various biomarkers, and microbiome methods were used. Tadpoles were exposed to 0 (control), 100, and 1000 μg/L of PS-MPs at both 25 °C and 32 °C for 28 days. The results showed that compared to low-temperature conditions, PS-MP exposure under high-temperature conditions significantly increased the total antioxidant capacity, glutathione, acid phosphatase, and lysozyme levels in the gut. Additionally, PS-MP exposure under 32 °C significantly disrupted the intestinal epithelial cell structure and increased the expression levels of pro-inflammatory factor genes. Gut microbiota analysis showed that the abundance of Cetobacterium continuously increasing with the concentration of PS-MPs. Under high-temperature conditions, PS-MP exposure further led to a decrease in microbial community diversity. These findings indicate that high-temperature environments exacerbate the negative effects of PS-MP exposure and enhance the oxidative stress and inflammatory response in the intestines of bullfrog tadpoles, which may be the primary factor leading to gut microbiota dysbiosis. This study provides scientific evidence for assessing the environmental risks of microplastics and formulating corresponding environmental protection measures, highlighting the urgency of addressing combined environmental stressors in the context of global warming.
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Affiliation(s)
- Zhilong Wang
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China
| | - Jun Xie
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China
| | - Guangjun Wang
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China
| | - Huirong Yang
- College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China
| | - Zhifei Li
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China
| | - Kai Zhang
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China
| | - Rui Shu
- Guangdong Xingwa Agricultural Technology Co., Ltd., Zhaoqing, 526070, China
| | - Wenping Xie
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China
| | - Jingjing Tian
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China
| | - Hongyan Li
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China
| | - Wangbao Gong
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China.
| | - Yun Xia
- Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China.
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Wei X, Leng X, Liang J, Liu J, Chi L, Deng H, Sun D. Pharmacological potential of natural medicine Astragali Radix in treating intestinal diseases. Biomed Pharmacother 2024; 180:117580. [PMID: 39413615 DOI: 10.1016/j.biopha.2024.117580] [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: 07/31/2024] [Revised: 10/07/2024] [Accepted: 10/14/2024] [Indexed: 10/18/2024] Open
Abstract
Due to changes in diet and lifestyle, the prevalence of intestinal diseases has been increasing annually. Current treatment methods exhibit several limitations, including adverse reactions and drug resistance, necessitating the development of new, safe, and effective therapies. Astragali Radix, a natural medicine utilized for over two millennia, offers unique advantages in treating intestinal ailments due to its multi-component and multi-target properties. This study aims to review the effective components of Astragali Radix that provide intestinal protection and to explore its pharmacological effects and molecular mechanisms across various intestinal diseases. This will provide a comprehensive foundation for using Astragali Radix in treating intestinal diseases and serve as a reference for future research directions. The active components of Astragali Radix with protective effects on the intestines include astragaloside (AS)-IV, AS-III, AS-II, astragalus polysaccharide (APS), cycloastagenol, calycosin, formononetin, and ononin. Astragali Radix and its active components primarily address intestinal diseases such as colorectal cancer (CRC), inflammatory bowel disease (IBD), and enterocolitis through mechanisms including anti-inflammatory actions, antioxidative stress responses, anti-proliferation and invasion activities, regulation of programmed cell death, immunoregulation, restoration of the intestinal epithelial barrier, and modulation of the intestinal microbiota and its metabolites. Consequently, Astragali Radix demonstrates significant intestinal protective activity and represents a promising natural treatment for intestinal diseases. However, the pharmacological actions and mechanisms of some active components in Astragali Radix remain unexplored. Moreover, further comprehensive toxicological and clinical studies are required to ascertain its safety and clinical effectiveness.
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Affiliation(s)
- Xiunan Wei
- First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
| | - Xiaohui Leng
- First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
| | - Junwei Liang
- Department of Gastroenterology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
| | - Jiahui Liu
- Department of Gastroenterology, Shandong Provincial Third Hospital, Jinan 250014, China.
| | - Lili Chi
- Department of Gastroenterology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
| | - Hualiang Deng
- Department of Gastroenterology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
| | - Dajuan Sun
- First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, China; Department of Gastroenterology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
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Mohammadgholi-Beiki A, Sheibani M, Jafari-Sabet M, Motevalian M, Rahimi-Moghaddam P. Anti-inflammatory and protective effects of Aripiprazole on TNBS-Induced colitis and associated depression in rats: Role of kynurenine pathway. Int Immunopharmacol 2024; 133:112158. [PMID: 38691917 DOI: 10.1016/j.intimp.2024.112158] [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: 02/06/2024] [Revised: 04/08/2024] [Accepted: 04/23/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND The prevalence of depression is higher in patients with inflammatory bowel disease (IBD) than in the general population. Inflammatory cytokines and the kynurenine pathway (KP) play important roles in IBD and associated depression. Aripiprazole (ARP), an atypical antipsychotic, shows various anti-inflammatory properties and may be useful in treating major depressive disorder. This study aimed to evaluate the protective effects of ARP on TNBS-induced colitis and subsequent depression in rats, highlighting the role of the KP. MATERIAL AND METHODS Fifty-six male Wistar rats were used, and all groups except for the normal and sham groups received a single dose of intra-rectal TNBS. Three different doses of ARP and dexamethasone were injected intraperitoneally for two weeks in treatment groups. On the 15th day, behavioral tests were performed to evaluate depressive-like behaviors. Colon ulcer index and histological changes were assessed. The tissue levels of inflammatory cytokines, KP markers, lipopolysaccharide (LPS), nuclear factor-kappa-B (NF-κB), and zonula occludens (ZO-1) were evaluated in the colon and hippocampus. RESULTS TNBS effectively induced intestinal damages and subsequent depressive-like symptoms in rats. TNBS treatment significantly elevated the intestinal content of inflammatory cytokines and NF-κB expression, dysregulated the KP markers balance in both colon and hippocampus tissues, and increased the serum levels of LPS. However, treatment with ARP for 14 days successfully reversed these alterations, particularly at higher doses. CONCLUSION ARP could alleviate IBD-induced colon damage and associated depressive-like behaviors mainly via suppressing inflammatory cytokines activity, serum LPS concentration, and affecting the NF-κB/kynurenine pathway.
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Affiliation(s)
| | - Mohammad Sheibani
- Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Razi Drug Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Majid Jafari-Sabet
- Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Razi Drug Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Manijeh Motevalian
- Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Razi Drug Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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Pekacar S, Özüpek B, Akkol EK, Taştan H, Ersan H, Orhan DD. Identification of bioactive components on antihemorrhoidal activity of Cistus laurifolius L. using RP-HPLC and LC-QTOF-MS. JOURNAL OF ETHNOPHARMACOLOGY 2024; 319:117122. [PMID: 37660958 DOI: 10.1016/j.jep.2023.117122] [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: 05/25/2023] [Revised: 08/30/2023] [Accepted: 08/31/2023] [Indexed: 09/05/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cistus laurifolius is widely used in folk medicine in Anatolia for the treatment of many ailments. The leaves of the plant are used in the form of tea in the treatment of hemorrhoids in the Western Black Sea Region and Central Anatolia. AIMS OF THE STUDY It was aimed at evaluating the anti-hemorrhoidal effects of C. laurifolus leaves in croton oil-induced hemorrhoid model in rats. MATERIALS AND METHODS The methanolic and aqueous extracts of C. laurifolius were tested for in vivo anti-hemorrhoidal efficacy using an experimental hemorrhoid model, followed by histological and biochemical analysis. Hemorrhoid was created by using croton oil on the anal region of the rats. TNF-α and VEGF mRNA expression levels were assessed using real-time PCR detections. The extract was also tested for anti-inflammatory properties, which are based on the suppression of an increase in capillary permeability caused by acetic acid. LC-QTOF-MS and RP-HPLC were used for the phytochemical analysis. RESULTS In comparison to the control, histological and biochemical assessment showed that the methanolic extract of C. laurifolius is particularly effective against hemorrhoids. The same extract group's TNF-α mRNA expression was found to be the lowest. Additionally, the methanolic extract showed a strong inhibitory effect on the increase in capillary permeability resulted on by acetic acid. Three phenolic compounds were discovered in the extracts by phytochemical analyses, while more than eighteen compounds were found by LC-QTOF-MS analysis. Five of these compounds are phenolic acid derivatives, and flavonoids constitute the majority of the group. CONCLUSION This is the first evidence from the research that C. laurifolius possesses strong anti-inflammatory and anti-hemorrhoidal properties.
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Affiliation(s)
- Sultan Pekacar
- Faculty of Pharmacy, Department of Pharmacognosy, Gazi University, 06330, Ankara, Turkey.
| | - Burçin Özüpek
- Faculty of Pharmacy, Department of Pharmacognosy, Gazi University, 06330, Ankara, Turkey.
| | - Esra Küpeli Akkol
- Faculty of Pharmacy, Department of Pharmacognosy, Gazi University, 06330, Ankara, Turkey.
| | - Hakkı Taştan
- Department of Biology, Faculty of Science, Gazi University, Etiler, 06330, Ankara, Turkey.
| | - Halil Ersan
- Hükümet Konağı Çocuk Büro Amirliği, Kapaklı, 59510, Tekirdağ, Turkey.
| | - Didem Deliorman Orhan
- Faculty of Pharmacy, Department of Pharmacognosy, Gazi University, 06330, Ankara, Turkey.
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Xue JC, Yuan S, Hou XT, Meng H, Liu BH, Cheng WW, Zhao M, Li HB, Guo XF, Di C, Li MJ, Zhang QG. Natural products modulate NLRP3 in ulcerative colitis. Front Pharmacol 2023; 14:1265825. [PMID: 37849728 PMCID: PMC10577194 DOI: 10.3389/fphar.2023.1265825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Accepted: 09/21/2023] [Indexed: 10/19/2023] Open
Abstract
Ulcerative colitis (UC) is a clinically common, progressive, devastating, chronic inflammatory disease of the intestine that is recurrent and difficult to treat. Nod-like receptor protein 3 (NLRP3) is a protein complex composed of multiple proteins whose formation activates cysteine aspartate protease-1 (caspase-1) to induce the maturation and secretion of inflammatory mediators such as interleukin (IL)-1β and IL-18, promoting the development of inflammatory responses. Recent studies have shown that NLRP3 is associated with UC susceptibility, and that it maintains a stable intestinal environment by responding to a wide range of pathogenic microorganisms. The mainstay of treatment for UC is to control inflammation and relieve symptoms. Despite a certain curative effect, there are problems such as easy recurrence after drug withdrawal and many side effects associated with long-term medication. NLRP3 serves as a core link in the inflammatory response. If the relationship between NLRP3 and gut microbes and inflammation-associated factors can be analyzed concerning its related inflammatory signaling pathways, its expression status as well as specific mechanism in the course of IBD can be elucidated and further considered for clinical diagnosis and treatment of IBD, it is expected that the development of lead compounds targeting the NLRP3 inflammasome can be developed for the treatment of IBD. Research into the prevention and treatment of UC, which has become a hotbed of research in recent years, has shown that natural products are rich in therapeutic means, and multi-targets, with fewer adverse effects. Natural products have shown promise in treating UC in numerous basic and clinical trials over the past few years. This paper describes the regulatory role of the NLRP3 inflammasome in UC and the mechanism of recent natural products targeting NLRP3 against UC, which provides a reference for the clinical treatment of this disease.
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Affiliation(s)
- Jia-Chen Xue
- Department of Nuclear Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
- Chronic Disease Research Center, Medical College, Dalian University, Dalian, Liaoning, China
- Department of Immunology and Pathogenic Biology, Yanbian University College of Basic Medicine, Yanji, Jilin, China
| | - Shuo Yuan
- Chronic Disease Research Center, Medical College, Dalian University, Dalian, Liaoning, China
- Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, China
| | - Xiao-Ting Hou
- Chronic Disease Research Center, Medical College, Dalian University, Dalian, Liaoning, China
| | - Huan Meng
- Chronic Disease Research Center, Medical College, Dalian University, Dalian, Liaoning, China
| | - Bao-Hong Liu
- Chronic Disease Research Center, Medical College, Dalian University, Dalian, Liaoning, China
| | - Wen-Wen Cheng
- Chronic Disease Research Center, Medical College, Dalian University, Dalian, Liaoning, China
| | - Ming Zhao
- Department of Nuclear Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
| | - Hong-Ben Li
- Department of Nuclear Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
| | - Xue-Fen Guo
- Department of Nuclear Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
| | - Chang Di
- Department of Nuclear Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
| | - Min-Jie Li
- Department of Nuclear Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China
| | - Qing-Gao Zhang
- Chronic Disease Research Center, Medical College, Dalian University, Dalian, Liaoning, China
- Department of Immunology and Pathogenic Biology, Yanbian University College of Basic Medicine, Yanji, Jilin, China
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Lee SY, Cho HY, Oh JP, Park J, Bae SH, Park H, Kim EJ, Lee JH. Therapeutic Effects of Combination of Nebivolol and Donepezil: Targeting Multifactorial Mechanisms in ALS. Neurotherapeutics 2023; 20:1779-1795. [PMID: 37782409 PMCID: PMC10684847 DOI: 10.1007/s13311-023-01444-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2023] [Indexed: 10/03/2023] Open
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor neurons in the spinal cord. Although the disease's pathophysiological mechanism remains poorly understood, multifactorial mechanisms affecting motor neuron loss converge to worsen the disease. Although two FDA-approved drugs, riluzole and edaravone, targeting excitotoxicity and oxidative stress, respectively, are available, their efficacies are limited to extending survival by only a few months. Here, we developed combinatorial drugs targeting multifactorial mechanisms underlying key components in ALS disease progression. Using data analysis based on the genetic information of patients with ALS-derived cells and pharmacogenomic data of the drugs, a combination of nebivolol and donepezil (nebivolol-donepezil) was identified for ALS therapy. Here, nebivolol-donepezil markedly reduced the levels of cytokines in the microglial cell line, inhibited nuclear factor-κB (NF-κB) nucleus translocation in the HeLa cell and substantially protected against excitotoxicity-induced neuronal loss by regulating the PI3K-Akt pathway. Nebivolol-donepezil significantly promoted the differentiation of neural progenitor cells (NPC) into motor neurons. Furthermore, we verified the low dose efficacy of nebivolol-donepezil on multiple indices corresponding to the quality of life of patients with ALS in vivo using SOD1G93A mice. Nebivolol-donepezil delayed motor function deterioration and halted motor neuronal loss in the spinal cord. Drug administration effectively suppressed muscle atrophy by mitigating the proportion of smaller myofibers and substantially reducing phospho-neurofilament heavy chain (pNF-H) levels in the serum, a promising ALS biomarker. High-dose nebivolol-donepezil significantly prolonged survival and delayed disease onset compared with vehicle-treated mice. These results indicate that the combination of nebivolol-donepezil efficiently prevents ALS disease progression, benefiting the patients' quality of life and life expectancy.
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Affiliation(s)
- Soo Yeon Lee
- DR. NOAH BIOTECH Inc., 91, Changnyong-daero 256beon-gil, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16229, Republic of Korea
| | - Hye-Yeon Cho
- DR. NOAH BIOTECH Inc., 91, Changnyong-daero 256beon-gil, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16229, Republic of Korea
| | - Jung-Pyo Oh
- DR. NOAH BIOTECH Inc., 91, Changnyong-daero 256beon-gil, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16229, Republic of Korea
| | - Jiae Park
- DR. NOAH BIOTECH Inc., 91, Changnyong-daero 256beon-gil, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16229, Republic of Korea
| | - Sang-Hun Bae
- DR. NOAH BIOTECH Inc., 91, Changnyong-daero 256beon-gil, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16229, Republic of Korea
| | - Haesun Park
- DR. NOAH BIOTECH Inc., 91, Changnyong-daero 256beon-gil, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16229, Republic of Korea
| | - Eun Jung Kim
- DR. NOAH BIOTECH Inc., 91, Changnyong-daero 256beon-gil, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16229, Republic of Korea.
| | - Ji-Hyun Lee
- DR. NOAH BIOTECH Inc., 91, Changnyong-daero 256beon-gil, Yeongtong-gu, Suwon-si, Gyeonggi-do, 16229, Republic of Korea.
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Zhu MZ, Yang MF, Song Y, Xu HM, Xu J, Yue NN, Zhang Y, Tian CM, Shi RY, Liang YJ, Yao J, Wang LS, Nie YQ, Li DF. Exploring the efficacy of herbal medicinal products as oral therapy for inflammatory bowel disease. Biomed Pharmacother 2023; 165:115266. [PMID: 37541177 DOI: 10.1016/j.biopha.2023.115266] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 07/30/2023] [Accepted: 07/31/2023] [Indexed: 08/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) encompasses a collection of idiopathic diseases characterized by chronic inflammation in the gastrointestinal (GI) tract. Patients diagnosed with IBD often experience necessitate long-term pharmacological interventions. Among the multitude of administration routes available for treating IBD, oral administration has gained significant popularity owing to its convenience and widespread utilization. In recent years, there has been extensive evaluation of the efficacy of orally administered herbal medicinal products and their extracts as a means of treating IBD. Consequently, substantial evidence has emerged, supporting their effectiveness in IBD treatment. This review aimed to provide a comprehensive summary of recent studies evaluating the effects of herbal medicinal products in the treatment of IBD. We delved into the regulatory role of these products in modulating immunity and maintaining the integrity of the intestinal epithelial barrier. Additionally, we examined their impact on antioxidant activity, anti-inflammatory properties, and the modulation of intestinal flora. By exploring these aspects, we aimed to emphasize the significant advantages associated with the use of oral herbal medicinal products in the treatment of IBD. Of particular note, this review introduced the concept of herbal plant-derived exosome-like nanoparticles (PDENs) as the active ingredient in herbal medicinal products for the treatment of IBD. The inclusion of PDENs offers distinct advantages, including enhanced tissue penetration and improved physical and chemical stability. These unique attributes not only demonstrate the potential of PDENs but also pave the way for the modernization of herbal medicinal products in IBD treatment.
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Affiliation(s)
- Min-Zheng Zhu
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China
| | - Mei-Feng Yang
- Department of Hematology, Yantian District People's Hospital, Shenzhen 518020, Guangdong, China
| | - Yang Song
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China; Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China
| | - Hao-Ming Xu
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China
| | - Jing Xu
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China
| | - Ning-Ning Yue
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University), Shenzhen 518020, Guangdong, China
| | - Yuan Zhang
- Department of Medical Administration, Huizhou Institute of Occupational Diseases Control and Prevention, Huizhou 516000, Guangdong, China
| | - Cheng-Mei Tian
- Department of Emergency, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
| | - Rui-Yue Shi
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China; Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China
| | - Yu-Jie Liang
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen 518020, Guangdong, China.
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China; Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China.
| | - Li-Sheng Wang
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China; Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China.
| | - Yu-Qiang Nie
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China.
| | - De-Feng Li
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China; Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China.
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Hou M, Leng Y, Shi Y, Tan Z, Min X. Astragalus membranaceus as a Drug Candidate for Inflammatory Bowel Disease: The Preclinical Evidence. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2023; 51:1501-1526. [PMID: 37530507 DOI: 10.1142/s0192415x23500684] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/03/2023]
Abstract
Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that include Crohn's disease (CD) and ulcerative colitis (UC). Today, IBD has no successful treatment. As a result, it is of paramount importance to develop novel therapeutic agents for IBD prevention and treatment. Astragalus membranaceus (AMS) is a traditional Chinese medicine found in the AMS root. Modern pharmacological studies indicate that AMS and its constituents exhibit multiple bioactivities, such as anti-inflammatory, anti-oxidant, immune regulatory, anticancer, hypolipidemic, hypoglycemic, hepatoprotective, expectorant, and diuretic effects. AMS and its active constituents, which have been reported to be effective in IBD treatment, are believed to be viable candidate drugs for IBD treatment. These underlying mechanisms are associated with anti-inflammation, anti-oxidation, immunomodulation, intestinal epithelial repair, gut microbiota homeostasis, and improved energy metabolism. In this review, we summarize the efficacy and underlying mechanisms involved in IBD treatment with AMS and its active constituents in preclinical studies.
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Affiliation(s)
- Min Hou
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, P. R. China
| | - Yufang Leng
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, P. R. China
- Department of Anesthesiology, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China
| | - Yajing Shi
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, P. R. China
| | - Zhiguo Tan
- The First Clinical Medical College, Lanzhou University, Lanzhou 730000, P. R. China
| | - Xiangzhen Min
- Department of Anesthesiology, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China
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Dong M, Li J, Yang D, Li M, Wei J. Biosynthesis and Pharmacological Activities of Flavonoids, Triterpene Saponins and Polysaccharides Derived from Astragalus membranaceus. Molecules 2023; 28:5018. [PMID: 37446680 PMCID: PMC10343288 DOI: 10.3390/molecules28135018] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 06/19/2023] [Accepted: 06/25/2023] [Indexed: 07/15/2023] Open
Abstract
Astragalus membranaceus (A. membranaceus), a well-known traditional herbal medicine, has been widely used in ailments for more than 2000 years. The main bioactive compounds including flavonoids, triterpene saponins and polysaccharides obtained from A. membranaceus have shown a wide range of biological activities and pharmacological effects. These bioactive compounds have a significant role in protecting the liver, immunomodulation, anticancer, antidiabetic, antiviral, antiinflammatory, antioxidant and anti-cardiovascular activities. The flavonoids are initially synthesized through the phenylpropanoid pathway, followed by catalysis with corresponding enzymes, while the triterpenoid saponins, especially astragalosides, are synthesized through the universal upstream pathways of mevalonate (MVA) and methylerythritol phosphate (MEP), and the downstream pathway of triterpenoid skeleton formation and modification. Moreover, the Astragalus polysaccharide (APS) possesses multiple pharmacological activities. In this review, we comprehensively discussed the biosynthesis pathway of flavonoids and triterpenoid saponins, and the structural features of polysaccharides in A. membranaceus. We further systematically summarized the pharmacological effects of bioactive ingredients in A. membranaceus, which laid the foundation for the development of clinical candidate agents. Finally, we proposed potential strategies of heterologous biosynthesis to improve the industrialized production and sustainable supply of natural products with pharmacological activities from A. membranaceus, thereby providing an important guide for their future development trend.
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Affiliation(s)
- Miaoyin Dong
- College of Life Science and Technology, Gansu Agricultural University, Lanzhou 730070, China; (M.D.); (D.Y.)
- State Key Laboratory of Arid Land Crop Science, Gansu Agricultural University, Lanzhou 730070, China
| | - Jinjuan Li
- Institute of Agricultural Quality Standards and Testing Technology, Gansu Academy of Agricultural Sciences, Lanzhou 730070, China;
| | - Delong Yang
- College of Life Science and Technology, Gansu Agricultural University, Lanzhou 730070, China; (M.D.); (D.Y.)
- State Key Laboratory of Arid Land Crop Science, Gansu Agricultural University, Lanzhou 730070, China
| | - Mengfei Li
- State Key Laboratory of Arid Land Crop Science, Gansu Agricultural University, Lanzhou 730070, China
- Agronomy College, Gansu Agricultural University, Lanzhou 730070, China
| | - Jianhe Wei
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
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10
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Bayer IS. Controlled Drug Release from Nanoengineered Polysaccharides. Pharmaceutics 2023; 15:pharmaceutics15051364. [PMID: 37242606 DOI: 10.3390/pharmaceutics15051364] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 04/18/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
Polysaccharides are naturally occurring complex molecules with exceptional physicochemical properties and bioactivities. They originate from plant, animal, and microbial-based resources and processes and can be chemically modified. The biocompatibility and biodegradability of polysaccharides enable their increased use in nanoscale synthesis and engineering for drug encapsulation and release. This review focuses on sustained drug release studies from nanoscale polysaccharides in the fields of nanotechnology and biomedical sciences. Particular emphasis is placed on drug release kinetics and relevant mathematical models. An effective release model can be used to envision the behavior of specific nanoscale polysaccharide matrices and reduce impending experimental trial and error, saving time and resources. A robust model can also assist in translating from in vitro to in vivo experiments. The main aim of this review is to demonstrate that any study that establishes sustained release from nanoscale polysaccharide matrices should be accompanied by a detailed analysis of drug release kinetics by modeling since sustained release from polysaccharides not only involves diffusion and degradation but also surface erosion, complicated swelling dynamics, crosslinking, and drug-polymer interactions. As such, in the first part, we discuss the classification and role of polysaccharides in various applications and later elaborate on the specific pharmaceutical processes of polysaccharides in ionic gelling, stabilization, cross-linking, grafting, and encapsulation of drugs. We also document several drug release models applied to nanoscale hydrogels, nanofibers, and nanoparticles of polysaccharides and conclude that, at times, more than one model can accurately describe the sustained release profiles, indicating the existence of release mechanisms running in parallel. Finally, we conclude with the future opportunities and advanced applications of nanoengineered polysaccharides and their theranostic aptitudes for future clinical applications.
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Affiliation(s)
- Ilker S Bayer
- Smart Materials, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy
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11
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Wang P, Yang Q, Yan Z, Huang X, Gao X, Gun S. Identification of MicroRNAs Regulating Clostridium perfringens Type C Infection in the Spleen of Diarrheic Piglets. Curr Issues Mol Biol 2023; 45:3193-3207. [PMID: 37185732 PMCID: PMC10136749 DOI: 10.3390/cimb45040208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 04/02/2023] [Accepted: 04/04/2023] [Indexed: 05/17/2023] Open
Abstract
Clostridium perfringens (C. perfringens) type C is one of the common bacteria in piglet diarrhea, which seriously affects the swine industry's development. The spleen plays crucial roles in the resistance and elimination of pathogenic microorganisms, and miRNAs play important roles in regulating piglet diarrhea caused by pathogens. However, the mechanism by which miRNAs in the spleen are involved in regulating C. perfringens type C causing diarrhea in piglets remains unclear. The expression profiles of the spleen miRNAs of 7-day-old piglets challenged by C. perfringens type C were studied using small RNA-sequencing in control (SC), susceptible (SS), and resistant (SR) groups. Eight-eight differentially expressed miRNAs were screened. The KEGG pathway analysis of target genes revealed that the miRNAs were involved in the MAPK, p53, and ECM-receptor interaction signaling pathways. NFATC4 was determined to be a direct target of miR-532-3p and miR-133b using a dual-luciferase reporter assay. Thus, miR-133b and miR-532-3p targeted to NFATC4 were likely involved to piglet resistance to C. perfringens type C. This paper provides the valuable resources to deeply understand the genetic basis of C. perfringens type C resistance in piglets and a solid foundation to identify novel markers of C. perfringens type C resistance.
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Affiliation(s)
- Pengfei Wang
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China
| | - Qiaoli Yang
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China
| | - Zunqiang Yan
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China
| | - Xiaoyu Huang
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China
| | - Xiaoli Gao
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China
| | - Shuangbao Gun
- College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Research Center for Swine Production Engineering and Technology, Gansu Agricultural University, Lanzhou 730070, China
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12
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Hu HC, Zhang W, Xiong PY, Song L, Jia B, Liu XL. Anti-inflammatory and antioxidant activity of astragalus polysaccharide in ulcerative colitis: A systematic review and meta-analysis of animal studies. Front Pharmacol 2022; 13:1043236. [PMID: 36532736 PMCID: PMC9755193 DOI: 10.3389/fphar.2022.1043236] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 11/18/2022] [Indexed: 09/26/2023] Open
Abstract
Background: Accumulated evidence indicates that astragalus polysaccharide (APS) may have a beneficial impact on ulcerative colitis (UC) by suppressing inflammation and decreasing oxidative stress. Nevertheless, the credibility of the evidence for this practice is unclear. Therefore, we intended to conduct a systematic review and meta-analysis of animal studies to assess the anti-inflammatory and antioxidant activity of APS when used in the treatment of UC. Methods: Electronic bibliographic databases including PubMed, EMBASE, Web of Science, Chinese Biomedical Literature (CBM), Wanfang Database, CQVIP Database and China National Knowledge Infrastructure (CNKI) were retrieved for relevant animal studies. The methodological quality of animal studies was evaluated based on the SYstematic Review Center for Laboratory animal Experimentation (SYRCLE's RoB tool). A meta-analysis was performed according to the Cochrane Handbook for Systematic Reviews of Interventions by using STATA 12.0 software. This study was registered with PROSPERO, number CRD42021272595. Results: Twenty qualified publications involving 591 animals were included in this study. There was a significant association of APS with levels of disease activity index (DAI), colon macroscopic damage index (CMDI), colon histopathologic score (CHS), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), superoxide dismutase (SOD) and malondialdehyde (MDA) compared with that in the control group. Sensitivity analysis that eliminated one study at each stage did not change these results. Egger's test and funnel plot showed that publication bias was existed. Conclusion: In this meta-analysis, APS treatment significantly mitigated colonic damage by reducing the levels of MPO, TNF-α, IL-6, IL-1β, and MDA and recovering the SOD activity. These results demonstrated a protective role of APS in the treatment of UC and showed that the anti-inflammatory and antioxidant activity were implicated in the underlying mechanisms. Hence, APS may represent a promising candidate for treating UC. However, due to potential publication bias, a cautious interpretation is needed. Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/).
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Affiliation(s)
| | | | | | | | - Bo Jia
- College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xing-Long Liu
- College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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13
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Lu S, Yuan Y, Chen F, Zheng Y, Li C, Cao J, Xia G, Liu Z, Shen X, He Y, Zhou D, Zhu K. Holothuria Leucospilota polysaccharides alleviate hyperlipidemia via alteration of lipid metabolism and inflammation-related gene expression. J Food Biochem 2022; 46:e14392. [PMID: 36111651 DOI: 10.1111/jfbc.14392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 08/05/2022] [Accepted: 08/29/2022] [Indexed: 01/13/2023]
Abstract
Hyperlipemia is becoming a chronic disease that threatens human health. At the same time, people pay more and more attention to hyperlipemia. Holothuria Leucospilota polysaccharide (HLP) has been reported to ameliorate hyperlipidemia in high-fat diet-induced rats. Therefore, this study aimed to explore further metabolomics' role in improving liver function and reveal its mechanism. After oral administration of HLP for 4 weeks, total cholesterol (TC) and triglycerides (TG) levels of the liver in 100 and 200 mg/kg HLP groups were both decreased significantly (p < .05). The results showed that serum AST and ALT activity decreased by professing to be convinced of HLP. HLP also exerted antioxidant activities and up-regulated the expression of ACC, CD36, TNF-α and NF-κB in the liver of diabetic rats. Six potential biomarkers were recognized by UPLC-Q-TOF/MS and OPLS-DA. HLP alleviated liver injury by regulating the contents of metabolic end products in the serum of hyperlipidemic rats, such as nadolol and glycodeoxycholic acid. The results indicated that HLP effectively relieved HFD-induced hyperlipidemia by regulating metabolic disorders. PRACTICAL APPLICATIONS: As a chronic disease, hyperlipidemia has attracted more and more attention. Studies have shown that HLP regulates dyslipidemia, oxidative damage and inflammation to relieve hyperlipidemia. It mainly improved the liver damage caused by hyperlipidemia by inhibiting the expression of hepatic lipogenesis, oxidative stress and inflammatory factors. At the same time, we also detected six metabolites, among which high GDCA content indicated serious liver damage. Therefore, in the future, it can be suggested that HLP may be used as a functional, active substance in health products to assist in relieving hyperlipidemia, and GDCA may be used as an essential metabolic marker for the degree of liver injury.
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Affiliation(s)
- Shanshan Lu
- Engineering Research Centre of Utilization of Tropical Polysaccharide Resources of MOE, School of Food Science and Engineering, Hainan University, Haikou, China
| | - Yiqiong Yuan
- Engineering Research Centre of Utilization of Tropical Polysaccharide Resources of MOE, School of Food Science and Engineering, Hainan University, Haikou, China
| | - Fei Chen
- Engineering Research Centre of Utilization of Tropical Polysaccharide Resources of MOE, School of Food Science and Engineering, Hainan University, Haikou, China
| | - Yuanping Zheng
- Engineering Research Centre of Utilization of Tropical Polysaccharide Resources of MOE, School of Food Science and Engineering, Hainan University, Haikou, China
| | - Chuan Li
- Engineering Research Centre of Utilization of Tropical Polysaccharide Resources of MOE, School of Food Science and Engineering, Hainan University, Haikou, China.,Collaborative Innovation Center of Provincial and ministerial co-construction for Marine Food Deep Processing, Dalian Polytechnic University, Dalian, China
| | - Jun Cao
- Engineering Research Centre of Utilization of Tropical Polysaccharide Resources of MOE, School of Food Science and Engineering, Hainan University, Haikou, China
| | - Guanghua Xia
- Engineering Research Centre of Utilization of Tropical Polysaccharide Resources of MOE, School of Food Science and Engineering, Hainan University, Haikou, China.,Collaborative Innovation Center of Provincial and ministerial co-construction for Marine Food Deep Processing, Dalian Polytechnic University, Dalian, China
| | - Zhongyuan Liu
- Engineering Research Centre of Utilization of Tropical Polysaccharide Resources of MOE, School of Food Science and Engineering, Hainan University, Haikou, China.,Collaborative Innovation Center of Provincial and ministerial co-construction for Marine Food Deep Processing, Dalian Polytechnic University, Dalian, China
| | - Xuanri Shen
- Engineering Research Centre of Utilization of Tropical Polysaccharide Resources of MOE, School of Food Science and Engineering, Hainan University, Haikou, China.,Collaborative Innovation Center of Provincial and ministerial co-construction for Marine Food Deep Processing, Dalian Polytechnic University, Dalian, China
| | - Yanfu He
- Engineering Research Centre of Utilization of Tropical Polysaccharide Resources of MOE, School of Food Science and Engineering, Hainan University, Haikou, China
| | - Dayong Zhou
- Collaborative Innovation Center of Provincial and ministerial co-construction for Marine Food Deep Processing, Dalian Polytechnic University, Dalian, China
| | - Kexue Zhu
- Spice and Beverage Research Institute, Chinese Academy of Tropical Agricultural Sciences, Wanning, China
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14
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Akkol EK, Karpuz B, Türkcanoğlu G, Coşgunçelebi FG, Taştan H, Aschner M, Khatkar A, Sobarzo-Sánchez E. The Phytochemical Profile and Biological Activity of Malva neglecta Wallr. in Surgically Induced Endometriosis Model in Rats. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27227869. [PMID: 36431970 PMCID: PMC9695446 DOI: 10.3390/molecules27227869] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 11/02/2022] [Accepted: 11/03/2022] [Indexed: 11/16/2022]
Abstract
Leaves and aerial parts of Malva neglecta Wallr. have been traditionally used in Anatolia for the treatment of pain, inflammation, hemorrhoids, renal stones, constipation, and infertility. This study investigated the effects of M. neglecta leaves in a rat endometriosis model. The dried plant material was extracted with n-hexane, ethyl acetate, and methanol, successively. Experimental endometriosis was surgically induced in six-week-old female, non-pregnant, Wistar albino rats by autotransplant of endometrial tissue to the abdominal wall. After twenty-eight days, rats were evaluated for a second laparotomy. Endometrial foci areas were assessed, and intraabdominal adhesions were scored. Rats were divided into five groups as control, n-hexane, ethyl acetate, methanol, and aqueous extracts, as well as reference. At the end of the treatment, all rats were sacrificed and endometriotic foci areas and intraabdominal adhesions were re-evaluated and compared with the previous findings. Moreover, peritoneal fluid was collected to detect tumor necrosis factor- α (TNF-α), vascular endothelial growth factor (VEGF), and interleukin-6 (IL-6) levels, and cDNA synthesis, and a quantitative real-time polymerase chain reaction (PCR) test was done. The phytochemical content of the most active extract was determined using High-Performance Liquid Chromatography (HPLC). Both endometrial volume and adhesion score decreased significantly in the group treated with methanol extract. In addition, significant decreases were observed in TNF-α, VEGF, and IL-6 levels in animals administered methanol extract. HPLC results showed that the activity caused by the methanol extract of M. neglecta was due to the polyphenols. Taken together, these novel findings indicate that M. neglecta may be a promising alternative for the treatment of endometriosis.
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Affiliation(s)
- Esra Küpeli Akkol
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey
- Correspondence: (E.K.A.); (E.S.-S.); Tel.: +90-(31)-22023185 (E.K.A.); +90-(56)-953972783 (E.S.-S.)
| | - Büşra Karpuz
- Department of Pharmacognosy, Faculty of Pharmacy, Başkent University, 06810 Ankara, Turkey
| | - Gizem Türkcanoğlu
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey
| | | | - Hakkı Taştan
- Department of Biology, Faculty of Science, Gazi University, 06560 Ankara, Turkey
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Anurag Khatkar
- Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India
| | - Eduardo Sobarzo-Sánchez
- Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
- Facultad de Ciencias de la Salud, Instituto de Investigación y Postgrado, Universidad Central de Chile, Santiago 8330507, Chile
- Correspondence: (E.K.A.); (E.S.-S.); Tel.: +90-(31)-22023185 (E.K.A.); +90-(56)-953972783 (E.S.-S.)
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15
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A Potential Role of Plant/Macrofungi/Algae-Derived Non-Starch Polysaccharide in Colitis Curing: Review of Possible Mechanisms of Action. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27196467. [PMID: 36235004 PMCID: PMC9573148 DOI: 10.3390/molecules27196467] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 09/23/2022] [Accepted: 09/23/2022] [Indexed: 11/09/2022]
Abstract
Multiple in vitro and in vivo model investigations have suggested a broad spectrum of potential mechanisms by which plant/macrofungi-derived non-starch polysaccharides may play a role in the treatment of inflammatory bowel disease (IBD). This article reviews the in vivo and in vitro evidence of different plant-derived polysaccharides for IBD therapy. Their underlying mechanisms, particularly the molecular mechanisms associated with protective effects in the treatment and prevention of IDB, have been well summarized, including anti-inflammatory, epithelial barrier repair, and the regulation of intestinal flora. Emerging studies have observed the potent role of probiotics in IBD, particularly its ability to modulate gut microbiota, a well-known key factor for IBD. In summary, plant/macrofungi-derived polysaccharides have the potential to be a promising agent for the adjuvant treatment and prevention of IBD and will contribute to the design of well-designed clinical intervention trials that will ultimately improve the therapy of IBD.
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16
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Li H, Cao W, Xie J, Che H, Liu L, Dong X, Song L, Xie W. α-D-1,6-glucan from Castanea mollissima Blume alleviates dextran sulfate sodium-induced colitis in vivo. Carbohydr Polym 2022; 289:119410. [DOI: 10.1016/j.carbpol.2022.119410] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 03/16/2022] [Accepted: 03/22/2022] [Indexed: 12/14/2022]
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17
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Zhang S, Luo H, Tan D, Peng B, Zhong Z, Wang Y. Holism of Chinese herbal medicine prescriptions for inflammatory bowel disease: A review based on clinical evidence and experimental research. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 102:154202. [PMID: 35665678 DOI: 10.1016/j.phymed.2022.154202] [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: 03/02/2022] [Revised: 05/17/2022] [Accepted: 05/22/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic nonspecific inflammatory disease that causes a heavy burden and lacks effective treatments. Chinese herbal medicine prescriptions (CHMPs), which are characterized by a synergistic usage of herbs, are widely used in the management of IBD. The molecular mechanisms of action of CHMP are still ambiguous as the canonical "one-compound-one-target" approach has difficulty describing the dynamic bioreactions among CHMP objects. It seems more flexible to define the holism of CHMP for IBD by employing high-throughput analysis. However, studies that discuss the development of CHMP in treating IBD in a holistic view are still lacking. PURPOSE This review appraised preclinical and clinical research to fully describe the anti-IBD capacity of CHMPs and discussed CHMPs' holistic characteristics that can contribute to better management of IBD. METHODS & RESULTS We screened clinical and preclinical references of CHMP being used as treatments for IBD. We discussed the complexity of IBD and the development of CHMP to present the sophistication of CHMP treatments. To describe the clinical effectiveness of CHMPs against IBD, we performed an umbrella review of CHMP-associated META analyses, in which 1174 records were filtered down to 12 references. Then, we discussed 14 kinds of CHMPs that had a long history of use and analyzed their mechanisms of action. Representative herbs were employed to provide a subordinate explanation for the whole prescription. As holism is the dominant characteristic of CHMPs, we explored applications of CHMPs for IBD with the help of omics, gut microbiome, and network pharmacology, which are potential approaches to a dynamic figure of bioactions of CHMPs. CONCLUSION This review is the first to discuss the potential of CHMPs to manage IBD in a holistic context and will provide inspiring explanations for CHMP applications for further product transformation and application to other diseases.
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Affiliation(s)
- Siyuan Zhang
- Macau Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China
| | - Hua Luo
- Macau Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China
| | - Dechao Tan
- Macau Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China
| | - Bo Peng
- Macau Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China
| | - Zhangfeng Zhong
- Macau Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China.
| | - Yitao Wang
- Macau Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China.
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18
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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: 38] [Impact Index Per Article: 12.7] [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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19
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Zhong QH, Zha SW, Lau ATY, Xu YM. Recent knowledge of NFATc4 in oncogenesis and cancer prognosis. Cancer Cell Int 2022; 22:212. [PMID: 35698138 PMCID: PMC9190084 DOI: 10.1186/s12935-022-02619-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 05/20/2022] [Indexed: 02/05/2023] Open
Abstract
Nuclear factor of activated T-cells, cytoplasmic 4 (NFATc4), a transcription factor of NFAT family, which is activated by Ca2+/calcineurin signaling. Recently, it is reported that aberrantly activated NFATc4 participated and modulated in the initiation, proliferation, invasion, and metastasis of various cancers (including cancers of the lung, breast, ovary, cervix, skin, liver, pancreas, as well as glioma, primary myelofibrosis and acute myelocytic leukemia). In this review, we cover the latest knowledge on NFATc4 expression pattern, post-translational modification, epigenetic regulation, transcriptional activity regulation and its downstream targets. Furthermore, we perform database analysis to reveal the prognostic value of NFATc4 in various cancers and discuss the current unexplored areas of NFATc4 research. All in all, the result from these studies strongly suggest that NFATc4 has the potential as a molecular therapeutic target in multiple human cancer types.
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Affiliation(s)
- Qiu-Hua Zhong
- Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041 People’s Republic of China
| | - Si-Wei Zha
- Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041 People’s Republic of China
| | - Andy T. Y. Lau
- Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041 People’s Republic of China
| | - Yan-Ming Xu
- Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041 People’s Republic of China
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Tang Z, Huang G. Extraction, structure, and activity of polysaccharide from Radix astragali. Biomed Pharmacother 2022; 150:113015. [PMID: 35468585 DOI: 10.1016/j.biopha.2022.113015] [Citation(s) in RCA: 76] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/19/2022] [Accepted: 04/19/2022] [Indexed: 11/30/2022] Open
Abstract
Radix astragali polysaccharide (RAP) is a water-soluble heteropolysaccharide. It is an immune promoter and regulator, and has antivirus, antitumor, anti-aging, anti-radiation, anti-stress, anti-oxidation and other activitys. The extraction, separation, purification, structure, activity and modification of RAP were summarized. Some extraction methods of RAP had been introduced, and the separation and purification methods of RAP were reviewed, and the structure and activity of RAP were highly discussed. Current derivatization of RAP was outlined. Through the above discussion that the yield of crude polysaccharides from Radix astragali by enzyme-assisted extraction was significantly higher than that by other extraction methods, but each extraction method had different extraction effects under certain conditions, and the activity efficiency of RAP was also different. Therefore, it is particularly important to optimize the extraction method with known better yield for the study of RAP. In addition, the purification and separation of RAP are the key factors affecting the yield and activity of RAP. At the same time, there are still few studies on the derivatiration of Radix astragali polysaccharide, but the researches in this area are very important. RAP also has many important pharmacological effects on human body, but its practical application needs further study. Finally, studies on the structure-activity relationship of RAP still need to be carried out by many scholars. This review would provide some help for further researches on various important applications of RAP.
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Affiliation(s)
- Zhenjie Tang
- Laboratory of Carbohydrate Science and Engineering, Chongqing Key Laboratory of Inorganic Functional Materials, Chongqing Normal University, Chongqing 401331, China
| | - Gangliang Huang
- Laboratory of Carbohydrate Science and Engineering, Chongqing Key Laboratory of Inorganic Functional Materials, Chongqing Normal University, Chongqing 401331, China.
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Li HL, Wei YY, Li XH, Zhang SS, Zhang RT, Li JH, Ma BW, Shao SB, Lv ZW, Ruan H, Zhou HG, Yang C. Diosmetin has therapeutic efficacy in colitis regulating gut microbiota, inflammation, and oxidative stress via the circ-Sirt1/Sirt1 axis. Acta Pharmacol Sin 2022; 43:919-932. [PMID: 34262136 PMCID: PMC8976001 DOI: 10.1038/s41401-021-00726-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023]
Abstract
Diosmetin (3',5,7 -trihydroxy-4'-methoxy flavone) is a natural flavonoid compound in the citrus species, it exhibits a variety of pharmacological activities, but little is known of its effects on colitis. In this study we evaluated the therapeutic effects of diosmetin on mouse models of chronic and acute colitis. Chronic colitis was induced in mice by drinking water containing 3% dextran sulfate sodium (DSS) from D0 to D8, followed by administration of diosmetin (25, 50 mg · kg-1 · d-1) for another 8 days. Acute colitis was induced by drinking water containing 5% DSS from D0 to D7, the mice concomitantly received diosmetin (25, 50 mg · kg-1 · d-1) from D1 to D7. During the experiments, body weight and disease activity index (DAI) were assessed daily. After the mice were sacrificed, colon tissue and feces samples were collected, and colon length was measured. We showed that in both models, diosmetin administration significantly decreased DAI score and ameliorated microscopic colon tissue damage; increased the expression of tight junction proteins (occludin, claudin-1, and zonula occludens-1), and reduced the secretion of proinflammatory cytokines IL-1β, IL-6, TNF-α, and Cox-2 in colon tissue. We found that diosmetin administration remarkably inhibited colon oxidative damage by adjusting the levels of intracellular and mitochondrial reactive oxygen species, GSH-Px, SOD, MDA and GSH in colon tissue. The protection of diosmetin against intestinal epithelial barrier damage and oxidative stress were also observed in LPS-treated Caco-2 and IEC-6 cells in vitro. Furthermore, we demonstrated that diosmetin markedly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, which inhibited oxidative stress and inflammation in vivo and in vitro. Diosmetin reversed the effects of si-circSirt1 and si-Sirt1 in LPS-treated Caco-2 and IEC-6 cells. When the gut microbiota was analyzed in the mouse model of colitis, we found that diosmetin administration modulated the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were crucial for inflammatory bowel disease. Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is activated by diosmetin. The results imply that diosmetin may be a novel candidate to alleviate DSS-induced colitis and can be a lead compound for future optimization and modification.
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Affiliation(s)
- Hai-long Li
- grid.216938.70000 0000 9878 7032The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350 China ,grid.488175.7High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin, 300350 China
| | - Yi-ying Wei
- grid.216938.70000 0000 9878 7032The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350 China ,grid.488175.7High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin, 300350 China
| | - Xiao-he Li
- grid.216938.70000 0000 9878 7032The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350 China ,grid.488175.7High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin, 300350 China
| | - Shan-shan Zhang
- grid.216938.70000 0000 9878 7032The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350 China ,grid.488175.7High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin, 300350 China
| | - Ruo-tong Zhang
- grid.216938.70000 0000 9878 7032The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350 China ,grid.488175.7High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin, 300350 China
| | - Jin-he Li
- grid.216938.70000 0000 9878 7032The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350 China ,grid.488175.7High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin, 300350 China
| | - Bo-wei Ma
- grid.216938.70000 0000 9878 7032The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350 China ,grid.488175.7High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin, 300350 China
| | - Shuai-bo Shao
- grid.216938.70000 0000 9878 7032The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350 China ,grid.488175.7High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin, 300350 China
| | - Zi-wei Lv
- grid.216938.70000 0000 9878 7032The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350 China ,grid.488175.7High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin, 300350 China
| | - Hao Ruan
- grid.216938.70000 0000 9878 7032The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350 China ,grid.488175.7High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin, 300350 China
| | - Hong-gang Zhou
- grid.216938.70000 0000 9878 7032The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350 China ,grid.488175.7High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin, 300350 China
| | - Cheng Yang
- grid.216938.70000 0000 9878 7032The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350 China ,grid.488175.7High-throughput Molecular Drug Screening Centre, Tianjin International Joint Academy of Biomedicine, Tianjin, 300350 China
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Chu S, Wang W, Zhang N, Liu T, Li J, Chu X, Zuo S, Ma Z, Ma D, Chu L. Protective effects of 18β-Glycyrrhetinic acid against myocardial infarction: Involvement of PI3K/Akt pathway activation and inhibiting Ca 2+ influx via L-type Ca 2+ channels. Food Sci Nutr 2021; 9:6831-6843. [PMID: 34925811 PMCID: PMC8645779 DOI: 10.1002/fsn3.2639] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 09/15/2021] [Accepted: 10/16/2021] [Indexed: 12/24/2022] Open
Abstract
18β-Glycyrrhetinic acid (18β-GA) is a component extracted from licorice. This study aimed to evaluate the effects of 18β-GA on isoproterenol (ISO)-induced acute myocardial infarction in rats and mice. Two consecutive days of subcutaneous injection of ISO (85 mg/kg/day) resulted in acute myocardial infarction. We examined the pathological changes, oxidative stress, inflammatory response, and expression of apoptosis in mouse hearts. The expressions of phosphoinositol-3-kinase (PI3K), protein kinase B (Akt), and the phosphorylation levels of PI3K (p-PI3K) and Akt (p-Akt) were determined by western blotting. The whole-cell patch-clamp technique was applied to observe the L-type Ca2+ currents, and the Ion Optix detection system was used for cell contraction and Ca2+ transient in isolated rat cardiac ventricular myocytes. In ISO-induced myocardial infarction, the J-point, heart rate, creatine kinase, lactate dehydrogenase, superoxide dismutase, catalase, malondialdehyde, glutathion, and reactive oxygen species decreased in mice after 18β-GA treatment. 18β-GA improved ISO-induced morphologic pathology, inhibited the inflammatory pathway response and cardiomyocyte apoptosis, and inhibited PI3K/Akt signaling. 18β-GA could significantly inhibit ICa-L, myocardial contraction, and Ca2+ transient. This study demonstrates that 18β-GA has cardioprotective effects on acute myocardial infarction, which may be related to inhibiting oxidative stress, inflammation, apoptosis via the PI3K/Akt pathway, and reducing cell contractility and Ca2+ concentration via L-type Ca2+ channels.
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Affiliation(s)
- Sijie Chu
- School of Basic MedicineHebei University of Chinese MedicineShijiazhuangChina
| | - Weijie Wang
- Department of SurgeryThe Second Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Ning Zhang
- School of Basic MedicineHebei University of Chinese MedicineShijiazhuangChina
| | - Tong Liu
- School of Basic MedicineHebei University of Chinese MedicineShijiazhuangChina
| | - Jing Li
- School of PharmacyHebei University of Chinese MedicineShijiazhuangChina
| | - Xi Chu
- Department of PharmacyThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina
| | - Saijie Zuo
- School of PharmacyHebei University of Chinese MedicineShijiazhuangChina
| | - Zhihong Ma
- School of Basic MedicineHebei University of Chinese MedicineShijiazhuangChina
- Department of Immunology and PathobiologyHebei University of Chinese MedicineShijiazhuangChina
| | - Donglai Ma
- School of PharmacyHebei University of Chinese MedicineShijiazhuangChina
| | - Li Chu
- School of PharmacyHebei University of Chinese MedicineShijiazhuangChina
- Hebei Key Laboratory of Integrative Medicine on Liver‐Kidney PatternsHebei University of Chinese MedicineShijiazhuangChina
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Chen Y, Wang J, Li J, Zhu J, Wang R, Xi Q, Wu H, Shi T, Chen W. Astragalus polysaccharide prevents ferroptosis in a murine model of experimental colitis and human Caco-2 cells via inhibiting NRF2/HO-1 pathway. Eur J Pharmacol 2021; 911:174518. [PMID: 34562468 DOI: 10.1016/j.ejphar.2021.174518] [Citation(s) in RCA: 91] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 09/17/2021] [Accepted: 09/18/2021] [Indexed: 02/08/2023]
Abstract
Ulcerative colitis (UC) is a relapsing and remitting inflammatory bowel disease (IBD), but current conventional drugs lack efficacy. Astragalus polysaccharide (APS) is an active ingredient of Astragalus membranaceus and has been shown to ameliorate experimental colitis. In the present study, we aimed to investigate how APS affects the ferroptosis of intestinal epithelial cells in dextran sulfate sodium (DSS)-induced experimental colitis in mice. Our data showed that APS administration attenuated total weight loss, colon length shortening, disease activity index (DAI) scores, histological damage, and the expression of inflammatory cytokines in the colon of DSS-challenged mice. Moreover, we observed that treatment with APS obviously inhibited ferroptosis in both DSS-challenged mice and RSL3-stimulated Caco-2 cells, as indicated by the decrease in the expression of ferroptosis-associated genes (PTGS2, FTH, and FTL) and the levels of surrogate ferroptosis markers (MDA, GSH, and iron load). Mechanistically, the inhibitory effects of APS on ferroptosis in DSS-challenged mice and RSL3-stimulated Caco-2 cells were associated with the NRF2/HO-1 pathway. Collectively, our findings identify a new role of APS in preventing ferroptosis in a murine model of experimental colitis and human Caco-2 cells via inhibiting NRF2/HO-1 pathway.
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Affiliation(s)
- Yanjun Chen
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Suzhou Key Laboratory for Tumor Immunology of Digestive Tract, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China
| | - Jiayu Wang
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Suzhou Key Laboratory for Tumor Immunology of Digestive Tract, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China
| | - Juntao Li
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China
| | - Jinghan Zhu
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China
| | - Ruoqin Wang
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China
| | - Qinhua Xi
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China
| | - Hongya Wu
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Suzhou Key Laboratory for Tumor Immunology of Digestive Tract, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, Jiangsu, 215000, China
| | - Tongguo Shi
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Suzhou Key Laboratory for Tumor Immunology of Digestive Tract, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, Jiangsu, 215000, China; Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China.
| | - Weichang Chen
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China; Suzhou Key Laboratory for Tumor Immunology of Digestive Tract, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China.
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Zhai R, Feng L, Zhang Y, Liu W, Li S, Hu Z. Combined Transcriptomic and Lipidomic Analysis Reveals Dysregulated Genes Expression and Lipid Metabolism Profiles in the Early Stage of Fatty Liver Disease in Rats. Front Nutr 2021; 8:733197. [PMID: 34604283 PMCID: PMC8484319 DOI: 10.3389/fnut.2021.733197] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 08/20/2021] [Indexed: 12/25/2022] Open
Abstract
Non-alcoholic fatty liver disease develops from simple steatosis to non-alcoholic steatohepatitis (NASH), which then potentially develops into liver cirrhosis. It is a serious threat to human health. Therefore, investigating the formation and development mechanism of non-alcoholic fatty liver disease (NAFLD) is of great significance. Herein, an early model of NAFLD was successfully established by feeding rats with a high-fat and choline-deficient diet. Liver tissue samples were obtained from rats in the fatty liver model group (NAFL) and normal diet control group (CON). Afterward, transcriptome and lipidomic analysis was performed. Transcriptome results revealed that 178 differentially expressed genes were detected in NAFL and CON groups. Out of which, 105 genes were up-regulated, 73 genes were downregulated, and 8 pathways were significantly enriched. A total of 982 metabolites were detected in lipidomic analysis. Out of which 474 metabolites were significantly different, 273 were up-regulated, 201 were downregulated, and 7 pathways were significantly enriched. Based on the joint analysis, 3 common enrichment pathways were found, including cholesterol metabolism and fat digestion and absorption metabolic pathways. Overall, in the early stage of NAFLD, a small number of genetic changes caused a strong response to lipid components. The strongest reflection was glycerides and glycerophospholipids. A significant increase in fatty acid uptake accompanied by cholesterol metabolism is the most prominent metabolic feature of the liver in the early stage of NAFLD. In the early stage of fatty liver, the liver had shown the characteristics of NASH.
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Affiliation(s)
- Ruina Zhai
- College of Animal Science, Xinjiang Agricultural University, Urumqi, China
| | - Lei Feng
- Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian, China
| | - Yu Zhang
- Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian, China
| | - Wei Liu
- Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian, China
| | - Shengli Li
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Zhiyong Hu
- Ruminant Nutrition and Physiology Laboratory, College of Animal Science and Technology, Shandong Agricultural University, Taian, China
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Duan L, Cheng S, Li L, Liu Y, Wang D, Liu G. Natural Anti-Inflammatory Compounds as Drug Candidates for Inflammatory Bowel Disease. Front Pharmacol 2021; 12:684486. [PMID: 34335253 PMCID: PMC8316996 DOI: 10.3389/fphar.2021.684486] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 07/02/2021] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel disease (IBD) represents chronic recurrent intestinal inflammation resulting from various factors. Crohn’s disease (CD) and ulcerative colitis (UC) have been identified as the two major types of IBD. Currently, most of the drugs for IBD used commonly in the clinic have adverse reactions, and only a few drugs present long-lasting treatment effects. Moreover, issues of drug resistance and disease recurrence are frequent and difficult to resolve. Together, these issues cause difficulties in treating patients with IBD. Therefore, the development of novel therapeutic agents for the prevention and treatment of IBD is of significance. In this context, research on natural compounds exhibiting anti-inflammatory activity could be a novel approach to developing effective therapeutic strategies for IBD. Phytochemicals such as astragalus polysaccharide (APS), quercetin, limonin, ginsenoside Rd, luteolin, kaempferol, and icariin are reported to be effective in IBD treatment. In brief, natural compounds with anti-inflammatory activities are considered important candidate drugs for IBD treatment. The present review discusses the potential of certain natural compounds and their synthetic derivatives in the prevention and treatment of IBD.
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Affiliation(s)
- Linshan Duan
- School of Pharmaceutical Sciences Xiamen University, Xiamen, China
| | - Shuyu Cheng
- Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, China
| | - Long Li
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China
| | - Yanling Liu
- School of Pharmaceutical Sciences Xiamen University, Xiamen, China
| | - Dan Wang
- Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, China
| | - Guoyan Liu
- School of Pharmaceutical Sciences Xiamen University, Xiamen, China.,Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, China.,Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China
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Li B, Yuan H, Li H, Luo B, Yu X, Wang Y, Liu W. Mechanism of Aquaporin-4 Up-Regulation After Traumatic Brain Injury and Preventative Action of Astragalus Polysaccharides in Mice. J BIOMATER TISS ENG 2021. [DOI: 10.1166/jbt.2021.2502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Here, we aimed to clarify the anti-inflammatory function of Astragalus Polysaccharides (APS), a chemical compound derived from Astragalus membranaceus, and the action of AQP4 on brain injury. We hypothesized that APS could improve the traumatic brain injury (TBI) outcome via
inhibiting expression of AQP4 in astrocytes. The present study elucidated that AQP4 was up-regulated and was effectively blocked by APS in mice with severe controlled cortical impact (CCI). Pre-treatment with APS effectively inhibited the up-regulation of AQP4 and diminished the neurological
deficits in mice. Additionally, primary astrocytes treated with mechanically-injured astrocyte supernatant, to mimic TBI in vitro, showed a significant up-regulation in swelling. We confirmed various signal molecules (NF-ĸB, MAPKs, and ERK) to have a role in astrocyte
swelling, after activation in trauma, and to be involved in the up-regulation of AQP4. These signal molecules also significantly decreased with APS treatment. In conclusion, our study suggests that APS attenuated neurological deficits and brain edema by decreasing AQP4 up-regulation in astrocytes
following TBI in mice, via reducing NF-ĸB, MAPKs, and the ERK signal molecules.
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Affiliation(s)
- Bin Li
- Department of Neurosurgery, The People’s Hospital of Hanchuan, Xiaogan 431600, Hubei, PR China
| | - Honggang Yuan
- Department of Neurosurgery, The People’s Hospital of Hanchuan, Xiaogan 431600, Hubei, PR China
| | - Huibing Li
- Department of Neurosurgery, The People’s Hospital of Hanchuan, Xiaogan 431600, Hubei, PR China
| | - Baochang Luo
- Department of Neurosurgery, The People’s Hospital of Hanchuan, Xiaogan 431600, Hubei, PR China
| | - Xiaoping Yu
- Department of Neurosurgery, The People’s Hospital of Hanchuan, Xiaogan 431600, Hubei, PR China
| | - Yanhua Wang
- Department of Neurosurgery, The People’s Hospital of Hanchuan, Xiaogan 431600, Hubei, PR China
| | - Wen Liu
- Department of Neurosurgery, The People’s Hospital of Hanchuan, Xiaogan 431600, Hubei, PR China
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Durmus A, Durmus I, Bender O, Karatepe O. The effect of Hericium erinaceum on the prevention of chemically induced experimental colitis in rats. Korean J Intern Med 2021; 36:S44-S52. [PMID: 32550720 PMCID: PMC8009150 DOI: 10.3904/kjim.2019.050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 12/18/2019] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND/AIMS The aim of this study is to investigate the effects of the Hericium erinaceum on an experimental colitis model. METHODS Twenty-four Wistar albino were included in this study. Rats were divided into three groups. Group 1 (n = 8) was sham group. Group 2 is the group of chemically induced by intrarectal administration of trinitrobenzene sulfonic acid (TNBS) resulting in colitis. Group 3 (n = 8) is the group that was treated 7 days before and 7 days after with H. erinaceum resulting in colitis. The activity of colitis was evaluated macroscopically and microscopically in rats. In other words, nitric oxide (NO) levels, malondialdehyde (MDA), interleukin 6 (IL-6), nuclear factor-kappa B (NF-κB) and, tumor necrosis factor-α (TNF-α) in addition to the myeloperoxidasem (MPO) activities was determined. RESULTS The rate of TNBS-induced colitis caused to increase the level of MDA activities meaningfully in the colitis group than the control group. The results indicated that MDA (p = 0.001), NO (p = 0.001), IL-6 (p = 0.001), MPO (p = 0.878), TNF-α (p = 0.001), and NF-κB levels of treatment group decreased in the blood and colon tissues because of the H. erinaceum treatment when compared to the colitis group. H. erinaceum treatment was related to the declining of MDA, NF-κB, NO, IL-6, and TNF-α levels. CONCLUSION H. erinaceum had a positive effect on the colitis by reducing oxidative damage in blood and tissue.
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Affiliation(s)
- Ali Durmus
- Department of Surgery, Nisantasi University, Istanbul, Turkey
| | - Ilgim Durmus
- Department of Medical Biotechnology, Acibadem University, Istanbul, Turkey
- Correspondence to Ilgim Durmus, Ph.D. Department of Medical Biotechnology, Acibadem University, İçerenköy Mahallesi, Kayışdağı Cd. No. 32, 34752, Ataşehir/Istanbul, Turkey Tel: +90-212-230-2008 Fax: +90-212-230-4949 E-mail:
| | - Omer Bender
- Department of SHMYO (Health Occupation School), Yeni Yuzyil University, Istanbul, Turkey
| | - Oguzhan Karatepe
- Department of SHMYO (Health Occupation School), Yeni Yuzyil University, Istanbul, Turkey
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Liao L, Li J, Li J, Huang Y, Wu Y. Effects of Astragalus polysaccharides on intestinal morphology and intestinal immune cells of Muscovy ducklings infected with Muscovy duck reovirus. Poult Sci 2021; 100:64-72. [PMID: 33357708 PMCID: PMC7772699 DOI: 10.1016/j.psj.2020.10.021] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 09/05/2020] [Accepted: 10/07/2020] [Indexed: 12/13/2022] Open
Abstract
Muscovy duck reovirus (MDRV) infection induces serious immunosuppression and intestinal injury in Muscovy ducklings with a high morbidity and mortality, and Astragalus polysaccharide (APS) pretreatment could efficiently protect ducklings from MDRV infection, although the underlying immunoregulatory mechanisms remain unclear. Thus, the objective of this study was to investigate effects of APS on the intestinal mucosal immunity in MDRV-infected Muscovy ducklings. A total of 190 1-day-old healthy Muscovy ducklings were randomly assigned to 3 groups (n = 50): normal control group, APS pretreatment for MDRV-infected group, and cohabitation infection group, then pretreated with 0.6 g/L APS or only drinking water followed by MDRV cohabitation infection with the remaining 40 artificially infected ducklings, respectively. At the 2, 3, 4, 6, 9 and 15 d after cohabitation infection, the intestinal samples were prepared to measure intestinal parameters including villus length, villus length/crypt depth (V/C) ratio, and wall thickness, together with counts of intraepithelial lymphocyte (IEL) and goblet cell (GC) by hematoxylin-eosin staining. Meanwhile, ileal secretory IgA (sIgA) and duodenal cytokine levels of IL-4, IL-6, IL-15, tumor necrosis factor-alpha, and interferon gamma were detected by the ELISA and radioimmunoassay, respectively. The results showed that APS significantly improved intestinal injuries of villi length, V/C ratio, and wall thickness of the small intestine infected with MDRV, effectively inhibited the reduction of IEL and GC caused by MDRV infection, subsequently increased sIgA and all the cytokine secretions at most time points, suggesting that APS pretreatment can effectively stimulate mucosal immune function by improving intestinal morphology and repair MDRV caused injures of small intestinal mucosal immune barrier in infected ducklings. Our findings lay the foundation for further application of APS in prevention and treatment of MDRV infection.
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Affiliation(s)
- Lvyan Liao
- College of Animal Science, Fujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of China; Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agricultural and Forestry University, Fuzhou 350002, People's Republic of China
| | - Jian Li
- College of Animal Science, Fujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of China; Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agricultural and Forestry University, Fuzhou 350002, People's Republic of China
| | - Jun Li
- College of Animal Science, Fujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of China
| | - Yifan Huang
- College of Animal Science, Fujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of China; Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agricultural and Forestry University, Fuzhou 350002, People's Republic of China
| | - Yijian Wu
- College of Animal Science, Fujian Agriculture and Forestry University, Fuzhou 350002, People's Republic of China; Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agricultural and Forestry University, Fuzhou 350002, People's Republic of China.
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Mohammed ASA, Naveed M, Jost N. Polysaccharides; Classification, Chemical Properties, and Future Perspective Applications in Fields of Pharmacology and Biological Medicine (A Review of Current Applications and Upcoming Potentialities). JOURNAL OF POLYMERS AND THE ENVIRONMENT 2021; 29:2359-2371. [PMID: 33526994 PMCID: PMC7838237 DOI: 10.1007/s10924-021-02052-2] [Citation(s) in RCA: 212] [Impact Index Per Article: 53.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 01/06/2021] [Indexed: 05/06/2023]
Abstract
Polysaccharides are essential macromolecules which almost exist in all living forms, and have important biological functions, they are getting more attention because they exhibit a wide range of biological and pharmacological activities, such as anti-tumour, immunomodulatory, antimicrobial, antioxidant, anticoagulant, antidiabetic, antiviral, and hypoglycemia activities, making them one of the most promising candidates in biomedical and pharmaceutical fields. Polysaccharides can be obtained from many different sources, such as plants, microorganisms, algae, and animals. Due to their physicochemical properties, they are susceptible to physical and chemical modifications leading to enhanced properties, which is the basic concept for their diverse applications in biomedical and pharmaceutical fields. In this review, we will give insight into the most recent updated applications of polysaccharides and their potentialities as alternatives for traditional and conventional therapies. Challenges and limitations for polysaccharides in pharmaceutical utilities are discussed as well.
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Affiliation(s)
- Aiman Saleh A. Mohammed
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Interdisciplinary Excellence Centre, University of Szeged, Szeged, 6720 Hungary
- Department of Pharmacology, Faculty of Pharmacy, University of Aden, Aden, Yemen
| | - Muhammad Naveed
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Interdisciplinary Excellence Centre, University of Szeged, Szeged, 6720 Hungary
| | - Norbert Jost
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Interdisciplinary Excellence Centre, University of Szeged, Szeged, 6720 Hungary
- ELKH-SZTE Research Group of Cardiovascular Pharmacology, Szeged, 6720 Hungary
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Niu X, Shang H, Chen S, Chen R, Huang J, Miao Y, Cui W, Wang H, Sha Z, Peng D, Zhu R. Effects of Pinus massoniana pollen polysaccharides on intestinal microenvironment and colitis in mice. Food Funct 2020; 12:252-266. [PMID: 33295902 DOI: 10.1039/d0fo02190c] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The stability of the intestinal microenvironment is the basis for maintaining the normal physiological activities of the intestine. On the contrary, disordered dynamic processes lead to chronic inflammation and disease pathology. Pinus massoniana pollen polysaccharide (PPPS), isolated from Taishan Pinus massoniana pollen, has been reported with extensive biological activities, including immune regulation. However, the role of PPPS in the intestinal microenvironment and intestinal diseases is still unknown. In this work, we initiated our investigation by using 16S rRNA high-throughput sequencing technology to assess the effect of PPPS on gut microbiota in mice. The result showed that PPPS regulated the composition of gut microbiota in mice and increased the proportion of probiotics. Subsequently, we established immunosuppressive mice using cyclophosphamide (CTX) and found that PPPS regulated the immunosuppressive state of lymphocytes in Peyer's patches (PPs). Moreover, PPPS also regulated systemic immunity by acting on intestinal PPs. PPPS alleviated lipopolysaccharide (LPS) -induced Caco2 cell damage, indicating that PPPS has the ability to reduce the damage and effectively improve the barrier dysfunction in Caco2 cells. In addition, PPPS alleviated colonic injury and relieved colitis symptoms in dextran sodium sulfate (DSS)-induced colitis mice. Overall, our findings indicate that PPPS shows a practical regulatory effect in the intestinal microenvironment, which provides an essential theoretical basis for us to develop the potential application value of PPPS further.
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Affiliation(s)
- Xiangyun Niu
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an, China. and Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an, China
| | - Hongqi Shang
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an, China. and Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an, China
| | - Siyan Chen
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an, China. and Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an, China
| | - Ruichang Chen
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an, China. and Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an, China
| | - Jin Huang
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an, China. and Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an, China
| | - Yongqiang Miao
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an, China. and Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an, China
| | - Wenping Cui
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an, China. and Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an, China
| | - Huan Wang
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an, China. and Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an, China
| | - Zhou Sha
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an, China. and Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an, China
| | - Duo Peng
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
| | - Ruiliang Zhu
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an, China. and Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an, China
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Sodium houttuyfonate enhances the intestinal barrier and attenuates inflammation induced by Salmonella typhimurium through the NF-κB pathway in mice. Int Immunopharmacol 2020; 89:107058. [DOI: 10.1016/j.intimp.2020.107058] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 08/28/2020] [Accepted: 09/27/2020] [Indexed: 02/07/2023]
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Niu W, Chen X, Xu R, Dong H, Yang F, Wang Y, Zhang Z, Ju J. Polysaccharides from natural resources exhibit great potential in the treatment of ulcerative colitis: A review. Carbohydr Polym 2020; 254:117189. [PMID: 33357839 DOI: 10.1016/j.carbpol.2020.117189] [Citation(s) in RCA: 137] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 09/29/2020] [Accepted: 09/30/2020] [Indexed: 02/08/2023]
Abstract
The incidence of ulcerative colitis (UC) is high. Despite the availability of various therapeutic agents for the treatment of UC, the routine treatment has limitations and serious side effects. Therefore, a new drug that safely and effectively treats UC is urgently needed. Polysaccharides from natural resources have recently become a hot topic of study for their therapeutic effects on UC. These effects are associated with the regulation of inflammatory cytokines, intestinal flora, and immune system and protection of the intestinal mucosa. This review focuses on the recent advances of polysaccharides from natural resources in the treatment of UC. The mechanisms and practicability of polysaccharides, including pectin, guar gum, rhamnogalacturonan, chitosan, fructan, psyllium, glycosaminoglycan, algal polysaccharides, polysaccharides from fungi and traditional Chinese medicine, and polysaccharide derivatives, are discussed in detail. The good efficacy and safety of polysaccharides make them promising drugs for treating UC.
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Affiliation(s)
- Wei Niu
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China
| | - Xiaoqing Chen
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China
| | - Ruling Xu
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China; Anhui University of Chinese Medicine, Hefei, PR China
| | - Huimin Dong
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China
| | - Fuyan Yang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China; Anhui University of Chinese Medicine, Hefei, PR China
| | - Yun Wang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China
| | - Zhenhai Zhang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China.
| | - Jianming Ju
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China.
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Molecular mechanisms of polysaccharides from Ziziphus jujuba Mill var. spinosa seeds regulating the bioavailability of spinosin and preventing colitis. Int J Biol Macromol 2020; 163:1393-1402. [DOI: 10.1016/j.ijbiomac.2020.07.229] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 07/15/2020] [Accepted: 07/23/2020] [Indexed: 12/12/2022]
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Comparative Transcriptome Analysis Reveals the Protective Mechanism of Glycyrrhinic Acid for Deoxynivalenol-Induced Inflammation and Apoptosis in IPEC-J2 Cells. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:5974157. [PMID: 33163144 PMCID: PMC7604610 DOI: 10.1155/2020/5974157] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 09/17/2020] [Accepted: 10/05/2020] [Indexed: 12/12/2022]
Abstract
Deoxynivalenol (DON) is the most common mycotoxin that frequently contaminates human food and animal feed, resulting in intestinal diseases and systemic immunosuppression. Glycyrrhinic acid (GA) exhibits various pharmacological activities. To investigate the protective mechanism of GA for DON-induced inflammation and apoptosis in IPEC-J2 cells, RNA-seq analysis was used in the current study. The IPEC-J2 cells were treated with the control group (CON), 0.5 μg/mL DON, 400 μg/mL GA, and 400 μg/mL GA+0.5 μg/mL DON (GAD) for 6 h. Results showed that 0.5 μg/mL DON exposure for 6 h could induce oxidative stress, inflammation, and apoptosis in IPEC-J2 cells. GA addition could specifically promote the proliferation of DON-induced IPEC-J2 cells in a dose- and time-dependent manner. In addition, GA addition significantly increased Bcl-2 gene expression (P < 0.05) and superoxide dismutase and catalase activities (P < 0.01) and decreased lactate dehydrogenase release, the contents of malonaldehyde, IL-8, and NF-κB (P < 0.05), the relative mRNA abundances of IL-6, IL-8, TNF-α, COX-2, NF-κB, Bax, and caspase 3 (P < 0.01), and the protein expressions of Bax and TNF-α. Moreover, a total of 1576, 289, 1398, and 154 differentially expressed genes were identified in CON vs. DON, CON vs. GA, CON vs. GAD, and DON vs. GAD, respectively. Transcriptome analysis revealed that MAPK, TNF, and NF-κB signaling pathways and some chemokines played significant roles in the regulation of inflammation and apoptosis induced by DON. GA may alleviate DON cytotoxicity via the TNF signaling pathway by downregulating IL-15, CCL5, and other gene expressions. These results indicated that GA could alleviate DON-induced oxidative stress, inflammation, and apoptosis via the TNF signaling pathway in IPEC-J2 cells.
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Semiz A, Ozgun Acar O, Cetin H, Semiz G, Sen A. Suppression of Inflammatory Cytokines Expression with Bitter Melon ( Momordica Charantia) in TNBS-instigated Ulcerative Colitis. J Transl Int Med 2020; 8:177-187. [PMID: 33062594 PMCID: PMC7534491 DOI: 10.2478/jtim-2020-0027] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND AND OBJECTIVE This study was aimed to elucidate the molecular mechanism of Momordica charantia (MCh), along with a standard drug prednisolone, in a rat model of colitis induced by trinitrobenzene sulfonic acid (TNBS). METHODS After the induction of the experimental colitis, the animals were treated with MCh (4 g/kg/day) for 14 consecutive days by intragastric gavage. The colonic tissue expression levels of C-C motif chemokine ligand 17 (CCL-17), interleukin (IL)-1β, IL-6, IL-23, interferon-γ (IFN-γ), nuclear factor kappa B (NF-kB), and tumor necrosis factor-α (TNF-α), were determined at both mRNA and protein levels to estimate the effect of MCh. Besides, colonic specimens were analyzed histopathologically after staining with hematoxylin and eosin. RESULTS The body weights from TNBS-instigated colitis rats were found to be significantly lower than untreated animals. Also, the IFN-γ, IL-1β, IL-6, Il-23, TNF-α, CCL-17, and NF-kB mRNA and protein levels were increased significantly from 1.86-4.91-fold and 1.46-5.50-fold, respectively, in the TNBS-instigated colitis group as compared to the control. Both the MCh and prednisolone treatment significantly reduced the bodyweight loss. It also restored the induced colonic tissue levels of IL-1β, IL-6, IFN-γ, and TNF-α to normal levels seen in untreated animals. These results were also supported with the histochemical staining of the colonic tissues from both control and treated animals. CONCLUSION The presented data strongly suggests that MCh has the anti-inflammatory effect that might be modulated through vitamin D metabolism. It is the right candidate for the treatment of UC as an alternative and complementary therapeutics.
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Affiliation(s)
- Asli Semiz
- Pamukkale University, Faculty of Technology, Department of Biomedical Engineering, Denizli20070, Turkey
| | - Ozden Ozgun Acar
- Pamukkale University, Seed Breeding & Genetic Application and Research CentreDenizli20070, Turkey
| | - Hulya Cetin
- Pamukkale University, Faculty of Medicine, Basic Medical Sciences-Histology and Embryology, Denizli20070, Turkey
| | - Gurkan Semiz
- Pamukkale University, Faculty of Arts and Sciences, Biology Department, 20070Denizli, Turkey
| | - Alaattin Sen
- Pamukkale University, Faculty of Arts and Sciences, Biology Department, 20070Denizli, Turkey
- Abdullah Gul University, Faculty of Life and Natural Sciences, Department of Molecular Biology and Genetics, 38080Kayseri, Turkey
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Chen Z, Liu L, Gao C, Chen W, Vong CT, Yao P, Yang Y, Li X, Tang X, Wang S, Wang Y. Astragali Radix (Huangqi): A promising edible immunomodulatory herbal medicine. JOURNAL OF ETHNOPHARMACOLOGY 2020; 258:112895. [PMID: 32330511 DOI: 10.1016/j.jep.2020.112895] [Citation(s) in RCA: 183] [Impact Index Per Article: 36.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Revised: 04/11/2020] [Accepted: 04/17/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Astragali Radix (AR, Huangqi in Chinese), the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or A. membranaceus (Fisch.) Bge., possesses diverse therapeutic effects against fatigue, dyspepsia, diarrhea, heart diseases, hepatitis, and anemia. In recent years, increasing evidence has indicated the multiple immunomodulatory activities of AR in preclinical and clinical studies. AIM OF THE REVIEW This review attempts to elaborate the immunomodulatory effects of AR and its potential application in the treatment of immune related diseases. MATERIALS AND METHODS A comprehensive literature search AR was carried out using multiple internationally recognized databases (including Web of Science, Google Scholar, PubMed, ScienceDirect, Wiley, ACS, Springer, Taylor & Francis, and CNKI). RESULTS The immunomodulatory effects of AR are closely attributed to its active constituents such as polysaccharides, saponins, and flavonoids. We also demonstrate that AR can be used as a potential therapeutic intervention for immune related diseases through regulating immune organs, mucosal immune, and immune system (innate immunity and acquired immunity). CONCLUSION AR promotes the development of immune organs, enhances mucosal immune function, increases the quantity and phagocytic capacity of innate immunity, promotes the maturation and differentiation of acquired immunity cells, and improves the expression of antibodies in acquired immunity. We believe that AR has a broad research space in the adjuvant treatment of immune related diseases, which could be a breakthrough point to improve the application value of AR.
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Affiliation(s)
- Zhejie Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
| | - Lijuan Liu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China; PU-UM Innovative Institute of Chinese Medical Sciences, Guangdong-Macau Traditional Chinese Medicine Technology Industrial Park Development Co., Ltd, Hengqin New Area, Zhuhai, China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Caifang Gao
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
| | - Weijie Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
| | - Chi Teng Vong
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
| | - Peifen Yao
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
| | - Yuhan Yang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
| | - Xiuzhu Li
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
| | - Xudong Tang
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Shengpeng Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
| | - Yitao Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
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Zhao X, Liu H, Wu Y, Hu N, Lei M, Zhang Y, Wang S. Intervention with the crude polysaccharides of Physalis pubescens L. mitigates colitis by preventing oxidative damage, aberrant immune responses, and dysbacteriosis. J Food Sci 2020; 85:2596-2607. [PMID: 32696986 DOI: 10.1111/1750-3841.15330] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/15/2020] [Accepted: 05/18/2020] [Indexed: 12/22/2022]
Abstract
In this study, a colitis mouse model induced by dextran sulfate sodium (DSS) was used to investigate the mechanisms of action of an extract of crude polysaccharides (POL) from Physalis pubescens L. as a dietary intervention for colitis. Our results showed that the administration of POL prior to DSS-induced colitis protected the colon mucosal layer; maintained intestinal barrier integrity; alleviated oxidative damage; and lowered neutrophil infiltration by downregulating intercellular cell adhesion molecule-1 and monocyte chemoattractant protein-1 expression. More importantly, POL pretreatment reduced the expression of the proinflammatory factors tumor necrosis factor-α, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), thereby modulating the nuclear factor-κB/iNOS-COX-2 signal transduction pathway. In addition, POL reversed DSS-induced gut dysbiosis, accompanied by reducing the relative abundance of Helicobacter, Mucispirillum, and Erysipelatoclostridium. In conclusion, POL ameliorated DSS-induced intestinal injury in mice, indicating that POL could be a useful dietary nutrient to protect against colitis. PRACTICAL APPLICATION: Physalis pubescens L. is an edible fruit. The results of this study show that the intervention with Physalis pubescens L. crude polysaccharides may help prevent ulcerative colitis.
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Affiliation(s)
- Xiuli Zhao
- State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology, Tianjin, China
| | - Hengchao Liu
- State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology, Tianjin, China
| | - Yajing Wu
- State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology, Tianjin, China
| | - Nan Hu
- State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology, Tianjin, China
| | - Ming Lei
- State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology, Tianjin, China
| | - Yan Zhang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin, China
| | - Shuo Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin, China
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Cheng H, Sun L, Shen D, Ren A, Ma F, Tai G, Fan L, Zhou Y. Beta-1,6 glucan converts tumor-associated macrophages into an M1-like phenotype. Carbohydr Polym 2020; 247:116715. [PMID: 32829842 DOI: 10.1016/j.carbpol.2020.116715] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 06/30/2020] [Accepted: 07/01/2020] [Indexed: 02/06/2023]
Abstract
Tumor-associated macrophages (TAMs) with an M2-like phenotype have been linked to immunosuppression and resistance to chemotherapies of cancer, thus targeting TAMs has been an attractive therapeutic strategy to cancer immunotherapy. We have reported that the β-D-(1→6) glucan (AAMP-A70) isolated from Amillariella Mellea could promote macrophage activation. The present study showed that the β-1,6-glucan could promote the transformation of M2-like macrophages to M1-like phenotype and inhibit the viability of colon cancer cells in vitro and in vivo. On a cellular mechanistic level, the β-1,6-glucan reset tumor-promoting M2-like macrophages to tumor-inhibiting M1-like phenotype via increasing the phosphorylation of Akt/NF-κB and MAPK. Further, TLR2 was identified as the receptor of β-1,6-glucan in the transformation effect. In addition, a very similar β-1,6-glucan with side chains of β-Glc or α-Galρ which was purified from Lentinus edodes showed same activities with those from Amillariella Mellea. Our findings shed light on the action mode of β-1,6-glucan in cancer immunotherapy.
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Affiliation(s)
- Hairong Cheng
- Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun, 130024, China
| | - Lin Sun
- Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun, 130024, China
| | - Danyang Shen
- Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun, 130024, China
| | - Ai Ren
- Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun, 130024, China
| | - Fangli Ma
- Infinitus (China) Company Ltd., Guangzhou, 510663, China
| | - Guihua Tai
- Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun, 130024, China
| | - Luodi Fan
- Infinitus (China) Company Ltd., Guangzhou, 510663, China.
| | - Yifa Zhou
- Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun, 130024, China.
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Tang X, Huang G, Zhang T, Li S. Elucidation of colon-protective efficacy of diosgenin in experimental TNBS-induced colitis: inhibition of NF-κB/IkB-α and Bax/Caspase-1 signaling pathways. Biosci Biotechnol Biochem 2020; 84:1903-1912. [PMID: 32525764 DOI: 10.1080/09168451.2020.1776590] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
The aim of present investigation was to elucidate the unrevealed beneficial role of diosgenin against an experimental model of TNBS (2,4,6-trinitrobenzenesufonic acid)-induced ulcerative colitis (UC). Colitis was induced in Sprague-Dawley rats by intrarectal administration of TNBS (in 50% ethanol). Then animals were treated with diosgenin (50, 100, and 200 mg/kg) for 14 days. Various biochemical, behavioral, molecular, and histological analysis was performed. Diosgenin significantly decreased (p < 0.05) TNBS-induced elevated colonic oxido-nitrosative damage, myeloperoxidase, hydroxyproline, mRNA expressions of proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IFN-γ) and inflammatory markers (iNOs and COX-2) induced by TNBS. Western blot analysis relevated that TNBS-induced up-regulated protein expressions of NF-κB, IκBα, Bax, and Caspase-1 were markedly decreased (p < 0.05) by diosgenin treatment. It also markedly ameliorated the histological insults induced in the colon by TNBS. In conclusion, diosgenin exerts its colon-protective efficacy probably through the inhibition of NF-κB/IkB-α and Bax/Caspase-1 signaling pathways to experimental TNBS-induced ulcerative colitis. ABBREVIATIONS ANOVA: Analysis of variance; 5-ASA: 5-aminosalicylic acid; Bax: Bcl-2-associated X protein; COX-2: Cyclooxygenase-2; DAI: Disease Activity Index; DMSO: Dimethyl sulfoxide; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase; GSH: Glutathione; HP: Hydroxyproline; IAEC: International Animal Ethics Committee; IBD: Inflammatory Bowel Disease; IBS: Inflammatory Bowel Syndrome; IL's: Interleukin's; IFN-γ: Interferon-gamma; IκBα: nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha; iNOs: Inducible nitric oxide synthase; LTB4: Leukotriene B4; MDA: Malondialdehyde; MPO: Myeloperoxidase; NO: Nitric Oxide; NF-κB: Nuclear Factor-κB; ROS: Reactive Oxygen Species; SOD: Superoxide Dismutase; TNBS: Trinitrobenzene Sulfonic Acid; TNF-α: Tumor necrosis factor-α.
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Affiliation(s)
- Xiaobo Tang
- Gastroenterology Department, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical , Nanchong, Sichuan, China
| | - Gengzhen Huang
- Gastroenterology Department, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical , Nanchong, Sichuan, China
| | - Tao Zhang
- Gastroenterology Department, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical , Nanchong, Sichuan, China
| | - Shiqing Li
- Gastroenterology Department, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical , Nanchong, Sichuan, China
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Awad A, Khalil SR, Hendam BM, Abd El-Aziz RM, Metwally MMM, Imam TS. Protective potency of Astragalus polysaccharides against tilmicosin- induced cardiac injury via targeting oxidative stress and cell apoptosis-encoding pathways in rat. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:20861-20875. [PMID: 32246429 DOI: 10.1007/s11356-020-08565-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 03/23/2020] [Indexed: 06/11/2023]
Abstract
Tilmicosin (Til) was purposed to be used in the treatment of a wide range of respiratory diseases in livestock. However, undesirable adverse effects, cardiac toxicity, in particular, may be associated with Til therapy. In the present study, the response of adult rats administered Til subcutaneously at different doses (10, 25, 50, 75, and 100 mg/kg b.w.; single injection) was evaluated. Astragalus polysaccharide (AP) at two doses (100 and 200 mg/kg b.w.; intraperitoneally) was investigated for its potential to counteract the cardiac influences, involving the oxidative stress-induced damage and apoptotic cell death, elicited by the Til treatment at a dose of 75 mg/kg b.w. in rats. Til induced mortalities and altered the levels of the biomarkers for the cardiac damage, particularly in the rats treated with the doses of 75 and 100 mg/kg b.w.; similarly, morphological alterations in cardiac tissue were seen at all studied doses. AP was found to cause a significant (P ˂ 0.05) decline in the levels of impaired cardiac injury markers (troponin, creatine phosphokinase, and creatine phosphokinase-MB), improvement in the antioxidant endpoints (total antioxidant capacity), and attenuation in the oxidative stress indices (total reactive oxygen species, 8-hydroxy-2-deoxyguanosine, lipid peroxides [malondialdehyde], and protein carbonyl), associated with a significant (P ˂ 0.05) modulation in the mRNA expression levels of the encoding genes (Bcl-2, Bax, caspase-3, P53, Apaf-1, and AIF), related to the intrinsic pathway of apoptotic cell death in the cardiac tissue. AP administration partially restored the morphological changes in the rat's heart. The highest protective efficacy of AP was recorded at a dose level of 200 mg/kg b.w. Taken together, these results indicated that AP is a promising cardioprotective compound capable of attenuating Til-induced cardiac impact by protecting the rat cardiac tissue from Til-induced apoptosis when administered concurrently with and after the Til injection.
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Affiliation(s)
- Ashraf Awad
- Animal Wealth Development Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
| | - Samah R Khalil
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44511, Egypt.
| | - Basma M Hendam
- Department of Husbandry and Development of Animal Wealth, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Reda M Abd El-Aziz
- Physiology Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
| | - Mohamed M M Metwally
- Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
| | - Tamer S Imam
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44511, Egypt
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Zheng Y, Ren W, Zhang L, Zhang Y, Liu D, Liu Y. A Review of the Pharmacological Action of Astragalus Polysaccharide. Front Pharmacol 2020; 11:349. [PMID: 32265719 PMCID: PMC7105737 DOI: 10.3389/fphar.2020.00349] [Citation(s) in RCA: 237] [Impact Index Per Article: 47.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Accepted: 03/09/2020] [Indexed: 12/24/2022] Open
Abstract
Astragalus membranaceus (A. membranaceus) is a type of traditional Chinese medicine with a long history of clinical application. It is used in the improvement and treatment of various diseases as medicine and food to invigorate the spleen and replenish qi. The main components of A. membranaceus are Astragalus polysaccharide (APS), flavonoids compounds, saponins compounds, alkaloids, etc. APS is the most important natural active component in A. membranaceus, and possesses multiple pharmacological properties. At present, APS possess the huge potential to develop a drug improving or treating different diseases. In this review, we reveal the potential approaches of pre-treating and preparation on APS as much as possible and the study on content of APS and its chemical composition including different monosaccharides. More importantly, this paper summarize pharmacological actions on immune regulation, such as enhancing the immune organ index, promoting the proliferation of immune cells, stimulating the release of cytokines, and affecting the secretion of immunoglobulin and conduction of immune signals; anti-aging; anti-tumor by enhancing immunity, inducing apoptosis of tumor cells and inhibiting the proliferation and transfer of tumor cells; antiviral effects; regulation of blood glucose such as type I diabetes mellitus, type II diabetes mellitus and diabetic complications; lipid-lowering; anti-fibrosis; antimicrobial activities and anti-radiation. It provided theoretical basis for the further research such as its structure and mechanism of action, and clinical application of APS.
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Affiliation(s)
- Yijun Zheng
- Provincial-level Key Laboratory for Molecular Medicine of Major Diseases and The Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and University, Gansu University of Chinese Medicine, Lanzhou, China
| | - Weiyu Ren
- Pharmacy College, Gansu University of Chinese Medicine, Lanzhou, China
| | - Lina Zhang
- School of Education, University of Leeds, Leeds, United Kingdom
| | - Yuemei Zhang
- Ophthalmology Department, First Hospital of Lanzhou University, Lanzhou, China
| | - Dongling Liu
- Provincial-level Key Laboratory for Molecular Medicine of Major Diseases and The Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and University, Gansu University of Chinese Medicine, Lanzhou, China
- Pharmacy College, Gansu University of Chinese Medicine, Lanzhou, China
| | - Yongqi Liu
- Provincial-level Key Laboratory for Molecular Medicine of Major Diseases and The Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and University, Gansu University of Chinese Medicine, Lanzhou, China
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Dong N, Li X, Xue C, Zhang L, Wang C, Xu X, Shan A. Astragalus polysaccharides alleviates LPS-induced inflammation via the NF-κB/MAPK signaling pathway. J Cell Physiol 2020; 235:5525-5540. [PMID: 32037545 DOI: 10.1002/jcp.29452] [Citation(s) in RCA: 137] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 01/03/2020] [Indexed: 02/06/2023]
Abstract
Early weaning usually causes intestinal disorders, enteritis, and diarrhea in young animals and human infants. Astragalus polysaccharides (APS) possesses anti-inflammatory activity. To study the anti-inflammatory mechanisms of APS and its potential effects on intestinal health, we performed an RNA sequencing (RNA-seq) study in lipopolysaccharide (LPS)-stimulated porcine intestinal epithelial cells (IPEC-J2) in vitro. In addition, LPS-stimulated BALB/c mice were used to study the effects of APS on intestinal inflammation in vivo. The results from the RNA-seq analysis show that there were 107, 756, and 5 differentially expressed genes in the control versus LPS, LPS versus LPS+APS, and control versus LPS+APS comparison groups, respectively. The results of Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways play significant roles in the regulation of inflammatory factors and chemokine expression by APS. Further verification of the above two pathways by using western blot and immunofluorescence analysis revealed that the gene expression levels of the phosphorylated p38 MAPK, ERK1/2, and NF-κB p65 were inhibited by APS, while the expression of IκB-α protein was significantly increased (p < .05), indicating that APS inhibits the production of inflammatory factors and chemokines by the inhibition of activation of the MAPK and NF-κB inflammatory pathways induced by LPS stimulation. Animal experiments further demonstrated that prefeeding APS in BALB/c mice can alleviate the expression of the jejunal inflammatory factors interleukin 6 (IL-6), IL-Iβ, and tumor necrosis factor-α induced by LPS stimulation and improve jejunal villus morphology.
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Affiliation(s)
- Na Dong
- Laboratory of Molecular Nutrition and Immunity, Northeast Agricultural University, Harbin, P.R. China
| | - Xinran Li
- Laboratory of Molecular Nutrition and Immunity, Northeast Agricultural University, Harbin, P.R. China
| | - Chenyu Xue
- Laboratory of Molecular Nutrition and Immunity, Northeast Agricultural University, Harbin, P.R. China
| | - Lei Zhang
- Laboratory of Molecular Nutrition and Immunity, Northeast Agricultural University, Harbin, P.R. China
| | - Chensi Wang
- Laboratory of Molecular Nutrition and Immunity, Northeast Agricultural University, Harbin, P.R. China
| | - Xinyao Xu
- Laboratory of Molecular Nutrition and Immunity, Northeast Agricultural University, Harbin, P.R. China
| | - Anshan Shan
- Laboratory of Molecular Nutrition and Immunity, Northeast Agricultural University, Harbin, P.R. China
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Guo G, Shi F, Zhu J, Shao Y, Gong W, Zhou G, Wu H, She J, Shi W. Piperine, a functional food alkaloid, exhibits inhibitory potential against TNBS-induced colitis via the inhibition of IκB-α/NF-κB and induces tight junction protein (claudin-1, occludin, and ZO-1) signaling pathway in experimental mice. Hum Exp Toxicol 2019; 39:477-491. [PMID: 31835924 DOI: 10.1177/0960327119892042] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Inflammatory bowel disease is a chronic immunoinflammatory disease of the gastrointestinal tract. Piperine, an alkaloid, has been reported to possess antioxidant, anti-inflammatory, antiapoptotic, and antiulcer potential. AIM To elucidate the plausible mechanisms of action of piperine on experimental trinitrobenzenesufonic acid (TNBS)-induced colitis by assessing various biochemical, molecular, histological, and ultrastructural modifications. METHODS Colitis was induced in male Sprague-Dawley rats via intrarectal instillation of TNBS. Then, the rats were treated with piperine (10, 20, and 40 mg/kg, p.o.) for 14 days. RESULTS TNBS induced significant (p < 0.05) colonic damage, which was assessed by disease activity index, macroscopic score, and stool consistency. The administration of piperine (20 and 40 mg/kg) significantly inhibited (p < 0.05) these damages. Treatments with piperine (20 and 40 mg/kg) notably inhibited (p < 0.05) the TNBS-induced elevation of oxido-nitrosative stress (superoxide dismutase, glutathione, malondialdehyde, and nitric oxide), 5-hydroxytryptamine, and hydroxyproline content in the colon. Furthermore, colonic inducible nitric oxide synthase (iNOs), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma, and cyclooxygenase-2 (COX-2) messenger RNA (mRNA) expressions were upregulated after TNBS instillation and piperine (20 and 40 mg/kg) significantly attenuated (p < 0.05) these elevated mRNA expressions. TNBS decreased the expressions of tight junction (TJ) protein (claudin-1, occludin, and zonula occludens-1 (ZO-1)) and increased the expressions of proapoptotic (caspase-1) protein. These expressions were markedly inhibited (p < 0.05) by piperine treatment. Histological and ultrastructural studies of transmission electron microscopy suggested that piperine significantly ameliorated (p < 0.05) TNBS-induced colonic aberrations. CONCLUSION Piperine ameliorated the progression of TNBS-induced colitis by modulating the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha/nuclear factor-kappa B signaling pathway, thus inhibiting the overexpression of proinflammatory cytokines (TNF-α and IL's), COX-2, iNOs, oxido-nitrosative stress, and proapoptotic proteins (caspase-1) that may improve the expression of TJ protein (claudin-1, occludin, and ZO-1).
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Affiliation(s)
- G Guo
- Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiao Tong University, Xian, China
| | - F Shi
- Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiao Tong University, Xian, China.,Department of General Surgery, The First Affiliated Hospital of Xi'an Jiao Tong University, Xian, China
| | - J Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Y Shao
- Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - W Gong
- Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - G Zhou
- Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China
| | - H Wu
- Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiao Tong University, Xian, China
| | - J She
- Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiao Tong University, Xian, China.,Department of General Surgery, The First Affiliated Hospital of Xi'an Jiao Tong University, Xian, China
| | - W Shi
- Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiao Tong University, Xian, China.,Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Meng X, Hu W, Wu S, Zhu Z, Lu R, Yang G, Qin C, Yang L, Nie G. Chinese yam peel enhances the immunity of the common carp (Cyprinus carpio L.) by improving the gut defence barrier and modulating the intestinal microflora. FISH & SHELLFISH IMMUNOLOGY 2019; 95:528-537. [PMID: 31678187 DOI: 10.1016/j.fsi.2019.10.066] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 10/25/2019] [Accepted: 10/29/2019] [Indexed: 06/10/2023]
Abstract
The Chinese yam peel (CYP) is a by-product of yam processing that is rich in various nutrients and a good source for feed additives. This study investigated the effects of CYP on the intestinal microbiota and gut defence barrier of the common carp (Cyprinus carpio L.). Different groups of experimental fish were fed a normal control diet (NC), a low CYP diet (LYP) and a high CYP diet (HYP) for 8 weeks. After the feeding trial, the fish were assessed for intestinal enzyme activity, intestinal histology, immune-related gene expression, intestinal SCFAs and intestinal microbiota. Our results indicated that the intestinal integrity and antioxidant enzyme (CAT and SOD) activity in the common carp were enhanced following CYP supplementation. The mRNA levels of anti-inflammatory (TGF-β), tight binding protein (occludin and ZO-1) and pathway factor genes (TLR4 and NF-κB) were significantly upregulated in the HYP group (P＜0.05), which was accompanied by an increase in the level of pro-inflammatory IL-1β in the gut (P＜0.05). High-throughput sequencing revealed that Fusobacteria, Proteobacteria, and Bacteroidetes bacteria were most abundant in the microbial community in the gut of the common carp. The relative abundances of Bacteroides, Flavobacterium and Lactobacillus were increased, while the abundances of pathogenic microorganisms such as Enterobacteriaceae, Shewanella, Pseudomonas and Vibrio were reduced after treatment with CYP. Furthermore, the concentrations of acetic acid, propionic acid, butyric acid and total short-chain fatty acids (SCFAs) in the gut were also increased (P＜0.05). Finally, our results revealed correlations between gut microbiota, SCFAs, non-specific immunity and antioxidant enzymes in CYP-fed carp. These results suggest that CYP-supplemented feed could improve the immunity of the common carp by modulating the intestinal microflora and enhancing the gut defence barrier and has the potential to be used as an immunostimulating feed additive in aquaculture.
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Affiliation(s)
- Xiaolin Meng
- College of Fisheries, Henan Normal University, Xinxiang, 453007, PR China; Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, Henan Normal University, Xinxiang, 453007, PR China
| | - Wenpan Hu
- College of Fisheries, Henan Normal University, Xinxiang, 453007, PR China
| | - Shengkui Wu
- College of Fisheries, Henan Normal University, Xinxiang, 453007, PR China
| | - Zhenxiang Zhu
- College of Fisheries, Henan Normal University, Xinxiang, 453007, PR China
| | - Ronghua Lu
- College of Fisheries, Henan Normal University, Xinxiang, 453007, PR China; Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, Henan Normal University, Xinxiang, 453007, PR China
| | - Guokun Yang
- College of Fisheries, Henan Normal University, Xinxiang, 453007, PR China; Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, Henan Normal University, Xinxiang, 453007, PR China
| | - Chaobin Qin
- College of Fisheries, Henan Normal University, Xinxiang, 453007, PR China; Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, Henan Normal University, Xinxiang, 453007, PR China
| | - Liping Yang
- College of Fisheries, Henan Normal University, Xinxiang, 453007, PR China; Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, Henan Normal University, Xinxiang, 453007, PR China
| | - Guoxing Nie
- College of Fisheries, Henan Normal University, Xinxiang, 453007, PR China; Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, Henan Normal University, Xinxiang, 453007, PR China.
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Zhao W, Zeng X, Meng F, Bi X, Xu D, Chen X, Li Q, Han Y. Structural characterization and in vitro-in vivo evaluation of effect of a polysaccharide from Sanguisorba officinalis on acute kidney injury. Food Funct 2019; 10:7142-7151. [PMID: 31595901 DOI: 10.1039/c9fo01891c] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
We report here an acidic polysaccharide, namely RSP-3, which ameliorates acute kidney injury and is obtained from Sanguisorba officinalis. We extracted and purified two polysaccharides from this herb based on the acidity and screened them for their effect in regulating the immunological activity of macrophages. Among them, RSP-3 exhibited significant anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated macrophages by decreasing TNF-α and IL-6 levels. Subsequently, we found that RSP-3 suppressed ER stress, reduced ROS production and blocked NF-κBp65 translocation. After fully characterizing RSP-3 with a series of analytical technologies, we tested its anti-acute kidney injury (AKI) effect in vivo. In a murine AKI model induced by LPS, treatment with RSP-3 effectively ameliorated renal function. Besides, it decreased the levels of TNF-α and IL-6 in serum and reduced macrophage infiltration in injured kidney tissue. In sum, RSP-3, with a significant protective effect against AKI by showing anti-inflammatory activity, may become a meaningful drug candidate for treatment of AKI.
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Affiliation(s)
- Wenwen Zhao
- Qingdao University Medical College, 308 Ningxia Road, Qingdao, Shandong 266021, China.
| | - Xi Zeng
- Qingdao University Medical College, 308 Ningxia Road, Qingdao, Shandong 266021, China.
| | - Fancheng Meng
- College of Pharmaceutical Sciences, Key Laboratory of Luminescent and Real-Time Analytical Chemistry, Southwest University, Chongqing, China
| | - Xiaolin Bi
- Nutrition Department, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Dahai Xu
- Qingdao University Medical College, 308 Ningxia Road, Qingdao, Shandong 266021, China.
| | - Xiuping Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
| | - Qiu Li
- College of Chemistry and Pharmaceutical, Qingdao Agricultural University, Qingdao 266109, China.
| | - Yantao Han
- Qingdao University Medical College, 308 Ningxia Road, Qingdao, Shandong 266021, China.
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Astragalus polysaccharides attenuated inflammation and balanced the gut microflora in mice challenged with Salmonella typhimurium. Int Immunopharmacol 2019; 74:105681. [PMID: 31220694 DOI: 10.1016/j.intimp.2019.105681] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 05/24/2019] [Accepted: 06/03/2019] [Indexed: 01/25/2023]
Abstract
Salmonella typhimurium (S. t.) is one of the main pathogens that causes acute gastroenteritis. To evaluate the anti-inflammatory mechanism of Astragalus polysaccharide (APS) in vivo and its influence on the intestinal flora, BALB/c mice were infected with S. t. to establish a model of diarrhea. The disease activity index (DAI) scores showed that APS attenuated S. t.-induced weight loss and diarrhea in mice. APS significantly reduced the index of the liver and spleen as well as the ALT and AST levels in serum (P < 0.05). Hematoxylin and eosin (H&E) results indicated that APS significantly increased jejunum villus height and crypt depth and reduced the infiltration of inflammatory cells (P < 0.05). Additionally, APS increased the tight junction (TJ) proteins expression levels of ZO-1, Occludin and Claudin-1 in the jejunum. The results of 16S rDNA showed that APS significantly increased the number of Lactobacillus and Bifidobacterium spp. to normal levels (compared with the control group). In addition, APS significantly decreased the mRNA expression levels of the proinflammatory cytokines TNF-α, IL-1β, IL-6 and IL-17 in the jejunum (P < 0.01) as well as the proteins expression levels of COX-2 and iNOS (P < 0.05). Western blot confirmed that prefeeding with APS inhibited S. t.-induced expression of TLR4 and MyD88 in the jejunum and further inhibited nuclear factor-κB (NF-κB) activation, including the nuclear translocation of the p65 NF-κB subunit and the phosphorylation and degradation of IκB-α. This was the key to APS inhibition of the production of inflammatory factors and inflammatory mediators in the jejunum.
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Huang C, Yao R, Zhu Z, Pang D, Cao X, Feng B, Paulsen BS, Li L, Yin Z, Chen X, Jia R, Song X, Ye G, Luo Q, Chen Z, Zou Y. A pectic polysaccharide from water decoction of Xinjiang Lycium barbarum fruit protects against intestinal endoplasmic reticulum stress. Int J Biol Macromol 2019; 130:508-514. [PMID: 30826406 DOI: 10.1016/j.ijbiomac.2019.02.157] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Revised: 02/16/2019] [Accepted: 02/27/2019] [Indexed: 02/05/2023]
Abstract
Neutral polysaccharides from Ningxia L. barbarum fruit have been reported with immunomodulatory and antioxidative biological activities. Few studies on pectic polysaccharides have been reported, especially not from the Xinjiang L. barbarum. In the present study, a pectic polysaccharide, XLBP-I-I, was obtained from water decoction of Xinjiang L. barbarum using anion exchange chromatography and gel filtration. The results from methanolysis, methylation, FT-IR and NMR experiments indicated that XLBP-I-I was a typical pectic polysaccharide. In vitro assay showed that XLBP-I-I could reduce the ER stress and UPR in tunicamycin insult IPEC-J2 cells, and further protect IPEC-J2 cells against apoptosis induced by ER stress. These results reveal a new perspective for pectic L. barbarum polysaccharides on intestine ER stress, and this elicited interests for its further applications.
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Affiliation(s)
- Chao Huang
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China
| | - Ruyu Yao
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China
| | - Zhongkai Zhu
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China
| | - Dejiang Pang
- Neuroscience & Metabolism Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China
| | - Xiyue Cao
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China
| | - Bin Feng
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, PR China
| | | | - Lixia Li
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China
| | - Zhongqiong Yin
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China
| | - Xingfu Chen
- Key Laboratory of Crop Ecophysiology and Farming System in Southwest China, Ministry of Agriculture, College of Agronomy, Sichuan Agricultural University, Chengdu 611130, PR China
| | - Renrong Jia
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China
| | - Xu Song
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China
| | - Gang Ye
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China
| | - Qihui Luo
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China
| | - Zhengli Chen
- Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China.
| | - Yuanfeng Zou
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China.
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Farag MR, Elhady WM, Ahmed SYA, Taha HSA, Alagawany M. Astragalus polysaccharides alleviate tilmicosin-induced toxicity in rats by inhibiting oxidative damage and modulating the expressions of HSP70, NF-kB and Nrf2/HO-1 pathway. Res Vet Sci 2019; 124:137-148. [PMID: 30901666 DOI: 10.1016/j.rvsc.2019.03.010] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Revised: 03/02/2019] [Accepted: 03/12/2019] [Indexed: 12/22/2022]
Abstract
The present study evaluated the toxic effects of Tilmicosin (TIL) on adult rats. The rats received a single subcutaneous injection of TIL at different doses (10, 25, 50, 75 and 100 mg/kg bw). TIL altered the biochemical parameters including liver and kidney function markers, glucose level and lipid profile as well as resulted in histopathological lesions in liver and adrenal glands mostly in rats exposed to 75 and 100 mg/kg bw. Then the role of Astragalus polysaccharide (APS) at 100 and 200 mg/kg bw, in modulating the toxic effects induced by high dose of TIL was evaluated. Single injection of TIL at a dose of 75 mg/kg bw was found to increase the activity of ALT, AST and ALP enzymes, induce the generation of reactive oxygen species (ROS) and decrease the total antioxidant capacity (TAC). TIL upregulated the hepatic mRNA expression of heat shock protein 70 (HSP70) and nuclear factor kappa B (NF-kB) while blocked the Nrf2/HO-1 mediated response. These changes were also associated with increasing tumer necrosis factor-alpha (TNF-α), interlukin1-beta (IL-1β) and nitric oxide levels. On the other hand, the results indicate that APS has a beneficial role particularly at high level in alleviating the stress and the hepatotoxic effects elicited by TIL injection in rats.
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Affiliation(s)
- Mayada Ragab Farag
- Forensic Medicine and Toxicology Department, Veterinary Medicine Faculty, Zagazig University, Zagazig 44519, Egypt.
| | - Wlaa M Elhady
- Forensic Medicine and Toxicology Department, Veterinary Medicine Faculty, Zagazig University, Zagazig 44519, Egypt
| | - Sarah Y A Ahmed
- Microbiology Department, Veterinary Medicine Faculty, Zagazig University, Zagazig 44519, Egypt
| | - Heba S A Taha
- Genetic Department, Faculty of Agriculture, Zagazig University, Zagazig 44519, Egypt
| | - Mahmoud Alagawany
- Poultry Department, Faculty of Agriculture, Zagazig University, Zagazig 44519, Egypt
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49
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Extraction, Structure, and Pharmacological Activities of Astragalus Polysaccharides. APPLIED SCIENCES-BASEL 2018. [DOI: 10.3390/app9010122] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
The Astragalus polysaccharides (APS) are important bioactive components of Astragali Radix, the dry root of Astragalus membranaceus, which has been used in traditional Chinese medicine. In this review, the extraction conditions and extraction rates of APS are first compared for water, microwave-assisted, ultrasonic wave, and enzymatic hydrolysis extraction methods. Some studies have also shown that different methods can be combined to improve the extraction rate of APS. Subsequently, the chemical composition and structure of APS are discussed, as related to the extraction and purification method. Most studies have shown that APS is mainly composed of glucose, in addition to rhamnose, galactose, arabinose, xylose, mannose, glucuronic acid, and galacturonic acid. We also reviewed studies on the modification of APS using chemical methods, including sulfated modification using the chlorosulfonic acid–pyridine method, which is commonly used for chemical modification of APS. Finally, the pharmacological activities and mechanisms of action of APS are summarized, with a special focus on its immunoregulatory, antitumor, anti-inflammatory, and antiviral effects. This review will serve as a valuable resource for the research on APS.
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50
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Xia YG, Wang TL, Yu SM, Liang J, Kuang HX. Structural characteristics and hepatoprotective potential of Aralia elata root bark polysaccharides and their effects on SCFAs produced by intestinal flora metabolism. Carbohydr Polym 2018; 207:256-265. [PMID: 30600007 DOI: 10.1016/j.carbpol.2018.11.097] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Revised: 11/13/2018] [Accepted: 11/29/2018] [Indexed: 12/29/2022]
Abstract
The structural characteristics of the polysaccharides from Aralia elata root barks (AERP) were systematically investigated by FT-IR, HPSEC-ELSD and colorimetric methods as well as by GCMS based monosaccharide compositions, Smith degradations, and methylation analysis. The result showed average molecular weights of AERP were between 42.7 kDa and 93.9 kDa. AERP was composed of Ara, Rha, GlcA, Man, Glc, and Gal in a molar ratio of 22.2: 10.3: 8.1: 32.7: 5.7: 21.2 along with a small number of sulfate (3.38%) and acetyl (4.87%) groups. The abundant glycosidic linkages of Man, Ara, Gal, and Rha were observed as more than 90% of all the monosaccharides detected. Studies to evaluate hepatoprotective potentials of AERP showed that they had potent hepatoprotective effects in vivo in carbon tetrachloride-induced acute liver injury (CIALI) in mice by histopathological evaluation, biochemical examinations and ELISA assays. GCMS was further used to determine the effects of AERP on the chemical profiles of nine common short-chain fatty acids (SCFAs) produced by intestinal flora metabolism in CIALI mice. These findings not only provide novel insights into the pharmacological actions of AERP on the protection from CIALI in mice, but they also demonstrate that determining SCFA profiles by targeted GC-MS metabolomics is an effective technique to investigate the molecular mechanisms of the effects of plant polysaccharides on intestinal flora metabolism.
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Affiliation(s)
- Yong-Gang Xia
- Key Laboratory of Chinese Materia Medica (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin 150040, PR China.
| | - Tian-Long Wang
- Key Laboratory of Chinese Materia Medica (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin 150040, PR China
| | - Si-Miao Yu
- Key Laboratory of Chinese Materia Medica (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin 150040, PR China
| | - Jun Liang
- Key Laboratory of Chinese Materia Medica (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin 150040, PR China
| | - Hai-Xue Kuang
- Key Laboratory of Chinese Materia Medica (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin 150040, PR China.
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