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Lin HH, Yu PR, Tseng CY, Lee MS, Chen JH. Protective Effects of Lotus Seedpod Extract on Hepatic Lipid and Glucose Metabolism via AMPK-Associated Mechanisms in a Mouse Model of Metabolic Syndrome and Oleic Acid-Induced HepG2 Cells. Antioxidants (Basel) 2025; 14:595. [PMID: 40427477 DOI: 10.3390/antiox14050595] [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: 03/13/2025] [Revised: 05/07/2025] [Accepted: 05/12/2025] [Indexed: 05/29/2025] Open
Abstract
Metabolic syndrome (MetS) poses considerable toxicological risks due to its association with an increased likelihood of metabolic dysfunction-associated steatotic liver disease (MASLD), and is characterized by hypertension, hyperglycemia, dyslipidemia, and obesity. This study aimed to investigate the therapeutic potential of flavonoid-rich lotus seedpod extract (LSE) in alleviating MetS and MASLD-related hepatic disturbances. In vivo, mice subjected to a high-fat diet (HFD) and streptozotocin (STZ) injection were supplemented with LSE or simvastatin for 6 weeks. Obesity indicators included body weight and epididymal fat, while insulin resistance was measured by fasting serum glucose, serum insulin, homeostasis model assessment-insulin resistance index (HOMA-IR), and oral glucose tolerance (OGTT). Also, the levels of serum lipid profiles and blood pressure were evaluated. Adipokines, proinflammatory cytokines, liver fat droplets, and peri-portal fibrosis were analyzed to clarify the mechanism of MetS. LSE significantly reduced the HFD/STZ-induced MetS markers better than simvastatin, as demonstrated by hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory effects. In vitro, LSE improved oleic acid (OA)-triggered phenotypes of MASLD in hepatocyte HepG2 cells by reducing lipid accumulation and enhancing cell viability. This effect might be mediated through proteins involved in lipogenesis that are downregulated by adenosine monophosphate-activated protein kinase (AMPK). In addition, LSE reduced reactive oxygen species (ROS) generation and glycogen levels, as demonstrated by enhancing insulin signaling involving reducing insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation and increasing glycogen synthase kinase 3 beta (GSK3β) and protein kinase B (PKB) expression. These benefits were dependent on AMPK activation, as confirmed by the AMPK inhibitor compound C. These results indicate that LSE exhibits protective effects against MetS-caused toxicological disturbances in hepatic carbohydrate and lipid metabolism, potentially contributing to its efficacy in preventing MASLD or MetS.
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Affiliation(s)
- Hui-Hsuan Lin
- Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, Taiwan
- Clinical Laboratory, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan
| | - Pei-Rong Yu
- Department of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan
| | - Chiao-Yun Tseng
- Department of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan
| | - Ming-Shih Lee
- Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, Taiwan
- Clinical Laboratory, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan
| | - Jing-Hsien Chen
- Clinical Laboratory, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan
- Department of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan
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Chen TT, Shan S, Chen YN, Li MQ, Zhang HJ, Li L, Gao PP, Li N, Huang Y, Li XL, Wei W, Sun WY. Deficiency of β-arrestin2 ameliorates MASLD in mice by promoting the activation of TAK1/AMPK signaling. Arch Pharm Res 2025; 48:384-403. [PMID: 40341987 DOI: 10.1007/s12272-025-01544-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 04/24/2025] [Indexed: 05/11/2025]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a liver manifestation of metabolic syndrome characterized by excessive hepatic lipid accumulation and lipid metabolism disorders. It has become the most common chronic liver disease worldwide. β-arrestin2 is a multifunctional scaffold protein that is among the most important regulatory molecules, and it exerts key roles in regulating various cellular processes, such as immune response, cellular collagen production, and inflammation. In the current study, we aimed to explore the function of β-arrestin2 in the development and progression of MASLD. Firstly, we observed that the expression of β-arrestin2 was upregulated in liver samples from patients with MASLD. Then, the western diet (WD) combined with CCl4 injection-induced MASLD was established in wild-type mice, and showed that liver β-arrestin2 expression was also gradually increased, and positively correlated with the degree of lipid metabolism disorder during MASLD progression. Ulteriorly, β-arrestin2 knockout (Arrb2 KO) mice were utilized to induce the MASLD model and found that β-arrestin2 deficiency significantly ameliorated lipid accumulation and inflammatory response in the liver of MASLD mice. Furthermore, the in vitro depletion and overexpression experiments showed that increased β-arrestin2 aggravated lipid accumulation via inhibiting the activation of the TAK1/AMPK pathway, which may be mediated by competitively binding to TAB1 with TAK1. These findings suggest that β-arrestin2 is essential to regulate intrahepatic lipid metabolism. Here, we provide a novel insight in understanding of the expression and function of β-arrestin2 in MASLD, demonstrating that it may be a potential therapeutic target for MASLD treatment.
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Affiliation(s)
- Ting-Ting Chen
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Shan Shan
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Ya-Ning Chen
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Meng-Qi Li
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Hui-Juan Zhang
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Ling Li
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Ping-Ping Gao
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Nan Li
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Yan Huang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Xiao-Lei Li
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Anhui Medical University, Hefei, 230032, Anhui, China
| | - Wei Wei
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Anhui Medical University, Hefei, 230032, Anhui, China.
| | - Wu-Yi Sun
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Anhui Medical University, Hefei, 230032, Anhui, China.
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Hao KX, Zhang YJ, Li YM, Zhong RF, Wang L, Chang X, Jiang JG, Zhu W. Polyphenols From Mallotus peltatus (Geiseler) Mull. Arg. Ameliorates FFA-Induced Hepatic Steatosis in L02 Cells and Reduces Lipid Accumulation in Caenorhabditis elegans. Mol Nutr Food Res 2025:e202400689. [PMID: 40207673 DOI: 10.1002/mnfr.202400689] [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: 08/26/2024] [Revised: 12/09/2024] [Accepted: 01/27/2025] [Indexed: 04/11/2025]
Abstract
Mallotus peltatus (Geiseler) Mull. Arg. (MPMA) is a specialty plant used to make tea in Hainan Province, China. However, its hypolipidemic activity has been rarely studied. In this study, three polyphenol fractions (MPMAP-1, MPMAP-2, and MPMAP-3) were purified from a 60% ethanol extract of MPMA, and the hypolipidemic activities were evaluated by establishing an FFA-induced L02 cell model to determine lipid accumulation, antioxidant enzyme activities, and gene levels related to the Nrf2/ARE pathway and lipid metabolism. In addition, noninduced and high glucose-induced models were established using Caenorhabditis elegans (C. elegans) to evaluate the lipid-lowering activity of MPMAP-1. The results showed that all three polyphenols could significantly inhibit lipid accumulation, reduce intracellular MDA content, and enhance the activities of CAT, SOD, and GPx in FFA-induced L02 cells. The qRT-PCR results indicated that the amount of fat accumulation in L02 cells could be regulated by modulating the relative expression of mRNA in the Nrf2/ARE signaling pathway and lipid metabolism pathway. The noninduced model and high glucose-induced model demonstrated that MPMAP-1 was able to reduce lipid accumulation and ROS levels and increase the activities of antioxidant enzymes in C. elegans. In summary, our results suggested that polyphenol compounds of MPMA may be a promising natural product for lipid-lowering.
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Affiliation(s)
- Ke-Xin Hao
- College of Food and Bioengineering, South China University of Technology, Guangzhou, China
| | - Ying-Jing Zhang
- College of Food and Bioengineering, South China University of Technology, Guangzhou, China
| | - Yi-Meng Li
- College of Food and Bioengineering, South China University of Technology, Guangzhou, China
- Dermatology Hospital, Southern Medical University, Guangzhou, China
| | - Rui-Fang Zhong
- College of Food and Bioengineering, South China University of Technology, Guangzhou, China
| | - Ling Wang
- The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China
- Department of Intensive Care Unit, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
| | - Xiao Chang
- The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China
- Department of Intensive Care Unit, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
| | - Jian-Guo Jiang
- College of Food and Bioengineering, South China University of Technology, Guangzhou, China
| | - Wei Zhu
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
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Zhra M, Elahi MA, Tariq A, Abu-Zaid A, Yaqinuddin A. Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma. Cells 2025; 14:466. [PMID: 40136715 PMCID: PMC11941559 DOI: 10.3390/cells14060466] [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] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 03/12/2025] [Accepted: 03/13/2025] [Indexed: 03/27/2025] Open
Abstract
Metabolic dysfunction leading to non-alcoholic fatty liver disease (NAFLD) exhibits distinct molecular and immune signatures that are influenced by factors like gut microbiota. The gut microbiome interacts with the liver via a bidirectional relationship with the gut-liver axis. Microbial metabolites, sirtuins, and immune responses are pivotal in different metabolic diseases. This extensive review explores the complex and multifaceted interrelationship between sirtuins and gut microbiota, highlighting their importance in health and disease, particularly metabolic dysfunction and hepatocellular carcinoma (HCC). Sirtuins (SIRTs), classified as a group of NAD+-dependent deacetylases, serve as crucial modulators of a wide spectrum of cellular functions, including metabolic pathways, the inflammatory response, and the process of senescence. Their subcellular localization and diverse functions link them to various health conditions, including NAFLD and cancer. Concurrently, the gut microbiota, comprising diverse microorganisms, significantly influences host metabolism and immune responses. Recent findings indicate that sirtuins modulate gut microbiota composition and function, while the microbiota can affect sirtuin activity. This bidirectional relationship is particularly relevant in metabolic disorders, where dysbiosis contributes to disease progression. The review highlights recent findings on the roles of specific sirtuins in maintaining gut health and their implications in metabolic dysfunction and HCC development. Understanding these interactions offers potential therapeutic avenues for managing diseases linked to metabolic dysregulation and liver pathology.
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Affiliation(s)
- Mahmoud Zhra
- Department of Anatomy and Genetics, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia;
| | - Muhammad Affan Elahi
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (M.A.E.); (A.A.-Z.)
| | - Aamira Tariq
- Department of Biosciences, COMSATS University Islamabad, Islamabad Campus, Islamabad 45550, Pakistan
| | - Ahmed Abu-Zaid
- Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (M.A.E.); (A.A.-Z.)
| | - Ahmed Yaqinuddin
- Department of Anatomy and Genetics, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia;
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He L, Yang G, Li T, Li W, Yang R. Metabolic profile of procyanidin A2 by human intestinal microbiota and their antioxidant and hypolipidemic potential in HepG2 cells. Eur J Nutr 2025; 64:113. [PMID: 40056191 DOI: 10.1007/s00394-025-03638-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 02/25/2025] [Indexed: 03/10/2025]
Abstract
PURPOSE Procyanidins have strong potential for antioxidation and decreasing hepatic fat accumulation thus preventing non-alcoholic fatty liver disease (NAFLD). Procyanidin A2 (PCA2), predominately found in cranberries, avocado, peanut red skins and litchi fruit pericarp, is poorly absorbed in the gastrointestinal tract. However, literatures about its metabolic profile by gut microbiota and effects on lipid metabolism are limited. Therefore, the metabolites of PCA2 by human intestinal microbiota as well as their antioxidant and hypolipidemic potential were investigated. METHODS PCA2 was incubated with human intestinal microbiota and the metabolites produced were characterized by UPLC-Q-TOF-MS. The antioxidant and hypolipidemic potential of PCA2 and its microbial metabolites (MPCA2) were evaluated and compared. RESULTS The metabolism of PCA2 resulted in the formation of 14 metabolites, and the highest antioxidant capacity values were reached after 6 h incubation. In addition, PCA2 and MPCA2 were effective in reducing oxidative stress and lipid accumulation induced by oleic acid (OA) in HepG2 cells. They significantly promoted the phosphorylation of AMP-activated protein kinase (AMPK) and thus stimulated hepatic lipolysis by up-regulating of the expression of carnitine palmitoyl transferase I (CPT-I) and suppressed hepatic lipogenesis by down-regulation of the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA) reductase, fatty acid synthase (FAS) and sterol regulatory element binding proteins 1c (SREBP-1c). CONCLUSION Our results indicated that PCA2 and MPCA2 were effective to prevent OA-induced lipid accumulation and oxidative stress in HepG2 cells, implying that microbial metabolites may play a crucial role in the realization of human health effects of PCA2.
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Affiliation(s)
- Liangqian He
- Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou, 510642, China
| | - Guangmei Yang
- School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China
| | - Tongyun Li
- Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou, 510642, China
| | - Wu Li
- School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China.
| | - Ruili Yang
- Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou, 510642, China.
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Rodriguez-Garcia D, Uceda C, Barahona L, Ruiz-Nuñez M, Ballesteros AO, Desmet T, Sanz-Aparicio J, Fernandez-Lobato M, Gonzalez-Alfonso JL, Plou FJ. Enzymatic modification of dihydromyricetin by glucosylation and acylation, and its effect on the solubility and antioxidant activity. Org Biomol Chem 2025; 23:1136-1145. [PMID: 39688129 DOI: 10.1039/d4ob01682c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2024]
Abstract
Although dihydromyricetin exhibits strong potential for pharmaceutical applications, its limited aqueous solubility, permeability and stability restrict its use. In this work, we have synthesized a series of glucosides and acyl-glucosides of dihydromyricetin that could increase the bioavailability of this molecule. First, the R134A variant of sucrose phosphorylase from Thermoanaerobacterium thermosaccharolyticum catalyzed the formation of three monoglucosides, and the major one was identified as dihydromyricetin 4'-O-α-D-glucopyranoside (>75% conversion yield). The molecular features that define this specificity for the 4'-OH phenolic group were investigated through induced-fit docking analysis of each potential derivative. Furthermore, the acylation of the 4'-monoglucoside with fatty acid vinyl esters (C8, C12, and C16) was performed with high efficiency using the lipase from Thermomyces lanuginosus. Three novel acyl derivatives of dihydromyricetin were characterized. Furthermore, the water solubility and antioxidant activity (ABTS, DPPH) of the synthesized compounds were measured, concluding that the location of the glucosyl moiety may affect their physicochemical properties and, as a result, their bioactivity.
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Affiliation(s)
| | - Carlos Uceda
- Instituto de Catálisis y Petroleoquímica, CSIC, 28049 Madrid, Spain.
| | - Laura Barahona
- Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, 28049, Madrid, Spain
| | - Marta Ruiz-Nuñez
- Instituto de Química Física Blas Cabrera, CSIC, 28006 Madrid, Spain
| | | | - Tom Desmet
- Centre for Synthetic Biology (CSB), Department of Biotechnology, Ghent University, 9000 Ghent, Belgium
| | | | - Maria Fernandez-Lobato
- Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, 28049, Madrid, Spain
| | | | - Francisco J Plou
- Instituto de Catálisis y Petroleoquímica, CSIC, 28049 Madrid, Spain.
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Yang Y, Shu X, Javed HU, Wu Q, Liu H, Han J, Zhou H. Dietary supplementation of poly-dihydromyricetin-fused zinc nanoparticles alleviates fatty liver hemorrhagic syndrome by improving antioxidant capacity, intestinal health and lipid metabolism of laying hens. Poult Sci 2024; 103:104301. [PMID: 39306955 PMCID: PMC11447411 DOI: 10.1016/j.psj.2024.104301] [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] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/28/2024] [Accepted: 09/03/2024] [Indexed: 10/06/2024] Open
Abstract
Fatty liver hemorrhagic syndrome is the main cause of noninfectious death of laying hens and results in substantial economic losses to the poultry industry. This study focused on evaluating the effects of Poly-dihydromyricetin-fused zinc nanoparticles (PDMY-Zn NPs) on antioxidant capacity, liver lipid metabolism, and intestinal health in laying hens. A total of 288 Jingfen laying hens (52 wk old) with similar body weights were randomly divided into 4 dietary groups with 6 replicates in each group for 8 wk. The control group received a basal diet, while the treatment groups were supplemented with PDMY-Zn NPs at levels of 200, 400, and 600 mg/kg, respectively. The results indicate that PDMY-Zn NPs supplementation can enhance antioxidant parameters (P < 0.05) in the blood and liver of laying hens. Simultaneously, it can mitigate vacuolar degeneration and inflammatory necrosis in hepatocytes, improve the relative expression level of related parameters associated with liver lipid metabolism and key regulatory genes (P < 0.05). Furthermore, it has been observed to reshape the composition and diversity of cecum microbes by increasing beneficial probiotics such as Lactobacillus and Prevotella, while also enhancing villi height and villi/crypt ratio in the duodenum and ileum (P < 0.05). Additionally, it elevates liver bile acid content along with the relative expression of key genes involved in liver synthesis (P < 0.05). In summary, PDMY-Zn NPs showed potential to alleviate fatty liver hemorrhagic syndrome by enhancing antioxidant capacity, regulating liver lipid metabolism, and maintaining intestinal health.
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Affiliation(s)
- Yuanting Yang
- Zhanjiang Experimental Station, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang 524013, China
| | - Xugang Shu
- College of Chemistry and Chemical Engineering, Zhongkai University of Agricultural Engineering, Guangzhou 510225, China
| | - Hafiz Umer Javed
- Guangxi College and University Key Laboratory of High-Value Utilization of Seafood and Prepared Food in Beibu Gulf, College of Food Engineering, Beibu Gulf University, Qinzhou 535011, China
| | - Qun Wu
- Zhanjiang Experimental Station, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang 524013, China
| | - Hu Liu
- Zhanjiang Experimental Station, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang 524013, China
| | - Jiancheng Han
- Zhanjiang Experimental Station, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang 524013, China
| | - Hanlin Zhou
- Zhanjiang Experimental Station, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang 524013, China.
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Xue P, You X, Ren L, Yue W, Ma Z. PPARγ-mediated amelioration of lipid metabolism abnormality by kaempferol. Arch Biochem Biophys 2024; 761:110154. [PMID: 39278305 DOI: 10.1016/j.abb.2024.110154] [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: 04/25/2024] [Revised: 09/04/2024] [Accepted: 09/12/2024] [Indexed: 09/18/2024]
Abstract
Kaempferol can exert biological functions by regulating various signaling pathways. This study evaluated the ameliorative effect of kaempferol on lipid accumulation using oleic acid and palmitic acid-treated HepG2 cells and high-fat diet mice. In vitro oil red O staining showed that kaempferol treatment improved lipid accumulation (p < 0.001 for TG content and p < 0.05 for TC content). Immunofluorescence, Western blot analysis and RT-qPCR showed that kaempferol could promote nuclear translocation of PPARγ and reduce the expression of PPARγ, C/EBPβ, and SREBP-1c. Dietary intervention with kaempferol could reduce the lipid accumulation in hepatocytes and inflammatory cell infiltration, as well as attenuated serum levels of IL-6 and TNF-α in HFD-fed mice (p < 0.001 for IL-6 and p < 0.01 for TNF-α at kaempferol 60 mg/kg/d). Meanwhile, histopathological examination revealed that there was no substantial damage or distinct inflammation lesions in organs at the experimental dose, including the heart, lung, kidney, and spleen. The aforementioned research findings can serve as references for further preclinical investigations on the potential of kaempferol to mitigate lipid accumulation.
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Affiliation(s)
- Peiyu Xue
- School of Biology and Food Engineering, Anyang Institute of Technology, Anyang, 455000, China
| | - Xinyong You
- School of Biology and Food Engineering, Anyang Institute of Technology, Anyang, 455000, China
| | - Li Ren
- College of Food Science and Engineering, Jilin University, Changchun, 130062, China
| | - Weiming Yue
- Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan, 250012, China.
| | - Zheng Ma
- Department of Thoracic Surgery, Qilu Hospital of Shandong University, Jinan, 250012, China.
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Naskar R, Ghosh A, Bhattacharya R, Chakraborty S. A critical appraisal of geroprotective activities of flavonoids in terms of their bio-accessibility and polypharmacology. Neurochem Int 2024; 180:105859. [PMID: 39265701 DOI: 10.1016/j.neuint.2024.105859] [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: 05/30/2024] [Revised: 09/03/2024] [Accepted: 09/09/2024] [Indexed: 09/14/2024]
Abstract
Flavonoids, a commonly consumed natural product, elicit health-benefits such as antioxidant, anti-inflammatory, antiviral, anti-allergic, hepatoprotective, anti-carcinogenic and neuroprotective activities. Several studies have reported the beneficial role of flavonoids in improving memory, learning, and cognition in clinical settings. Their mechanism of action is mediated through the modulation of multiple signalling cascades. This polypharmacology makes them an attractive natural scaffold for designing and developing new effective therapeutics for complex neurological disorders like Alzheimer's disease and Parkinson's disease. Flavonoids are shown to inhibit crucial targets related to neurodegenerative disorders (NDDs), including acetylcholinesterase, butyrylcholinesterase, β-secretase, γ-secretase, α-synuclein, Aβ protein aggregation and neurofibrillary tangles formation. Conserved neuro-signalling pathways related to neurotransmitter biogenesis and inactivation, ease of genetic manipulation and tractability, cost-effectiveness, and their short lifespan make Caenorhabditis elegans one of the most frequently used models in neuroscience research and high-throughput drug screening for neurodegenerative disorders. Here, we critically appraise the neuroprotective activities of different flavonoids based on clinical trials and epidemiological data. This review provides critical insights into the absorption, metabolism, and tissue distribution of various classes of flavonoids, as well as detailed mechanisms of the observed neuroprotective activities at the molecular level, to rationalize the clinical data. We further extend the review to critically evaluate the scope of flavonoids in the disease management of neurodegenerative disorders and review the suitability of C. elegans as a model organism to study the neuroprotective efficacy of flavonoids and natural products.
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Affiliation(s)
- Roumi Naskar
- Center for Innovation in Molecular and Pharmaceutical Sciences (CIMPS), Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, 500046, India
| | - Anirrban Ghosh
- Amity Institute of Biotechnology, Amity University, Kolkata, 700135, India
| | - Raja Bhattacharya
- Amity Institute of Biotechnology, Amity University, Kolkata, 700135, India.
| | - Sandipan Chakraborty
- Center for Innovation in Molecular and Pharmaceutical Sciences (CIMPS), Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, 500046, India.
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10
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Liang M, Dong S, Guo Y, Zhang Y, Xiao X, Ma J, Jiang X, Yu W. Exploration of the potential mechanism of aqueous extract of Artemisia capillaris for the treatment of non-alcoholic fatty liver disease based on network pharmacology and experimental verification. J Pharm Pharmacol 2024; 76:1328-1339. [PMID: 39186724 DOI: 10.1093/jpp/rgae061] [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: 01/10/2024] [Accepted: 08/06/2024] [Indexed: 08/28/2024]
Abstract
OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is a nutritional and metabolic disease with a high prevalence today. Artemisia capillaris has anti-inflammatory, antioxidant, and other effects. However, the mechanism of A. capillaris in treating NAFLD is still poorly understood. METHODS This study explored the mechanism of A. capillaris in the treatment of NAFLD through network pharmacology and molecular docking, and verified the results through in vivo experiments using a high-fat diet-induced mouse model and in vitro experiments using an oleic acid-induced HepG2 cell model. KEY FINDINGS Aqueous extract of A. capillaris (AEAC) can reduce blood lipids, reduce liver lipid accumulation and liver inflammation in NAFLD mice, and improve NAFLD. Network pharmacology analysis revealed that 51 drug ingredients in A. capillaris correspond to 370 targets that act on NAFLD. GEO data mining obtained 93 liver differentially expressed genes related to NAFLD. In the UHPLC-MS detection results, 36 components were characterized and molecular docked with JNK. Verified in vitro and in vivo, the results show that JNK and the phosphorylation levels of IL-6, IL-1β, c-Jun, c-Fos, and CCL2 are key targets and pathways. CONCLUSIONS This study confirmed that AEAC reduces lipid accumulation and inflammation in the liver of NAFLD mice by inhibiting the JNK/AP-1 pathway.
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Affiliation(s)
- Meng Liang
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China
| | - Siyu Dong
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China
| | - Yi Guo
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China
| | - Yuyi Zhang
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China
| | - Xiao Xiao
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China
| | - Jun Ma
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China
- Institute of Chinese Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China
- Heilongjiang Provincial Key Laboratory for Prevention and Control of Common Animal Diseases, Northeast Agricultural University, Harbin, 150030, China
| | - Xiaowen Jiang
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China
| | - Wenhui Yu
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China
- Institute of Chinese Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China
- Heilongjiang Provincial Key Laboratory for Prevention and Control of Common Animal Diseases, Northeast Agricultural University, Harbin, 150030, China
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11
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Wang W, Xu M, Diao H, Long Q, Gan F, Mao Y. Effects of grape seed proanthocyanidin extract on cholesterol metabolism and antioxidant status in finishing pigs. Sci Rep 2024; 14:21117. [PMID: 39256553 PMCID: PMC11387843 DOI: 10.1038/s41598-024-72075-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 09/03/2024] [Indexed: 09/12/2024] Open
Abstract
Grape seed proanthocyanidin extract (GSPE) is a natural polyphenolic compound, which plays an important role in anti-inflammatory and antioxidant. The present study aimed to investigate the effects of GSPE supplementation on the cholesterol metabolism and antioxidant status of finishing pigs. In longissimus dorse (LD) muscle, the data showed that GSPE significantly decreased the contents of total cholesterol (T-CHO) and triglyceride (TG), and decreased the mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) and Fatty acid synthase (FAS), while increased the mRNA expression of carnitine palmitoyl transferase-1b (CPT1b), peroxisome proliferator-activated receptors (PPARα) and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). GSPE also reduced the enzyme activities of HMG-CoAR and FAS, and meanwhile amplified the activity of CPT1b in LD muscle of finishing pigs. Furthermore, dietary GSPE supplementation increased the serum catalase (CAT) and total antioxidant capacity (T-AOC), serum and liver total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) levels, while reduced serum and liver malondialdehyde (MDA) level in finishing pigs. In the liver, Superoxide Dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase 1 (GPX1), Nuclear Factor erythroid 2-Related Factor 2 (NRF2) mRNA levels were increased by GSPE. In conclusion, this study showed that GSPE might be an effective dietary supplement for improving cholesterol metabolism and antioxidant status in finishing pigs.
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Affiliation(s)
- Wenjing Wang
- College of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu, 610041, China
| | - Meng Xu
- College of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu, 610041, China.
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, 610041, China.
- Key Laboratory of Animal Science of National Ethnic Affairs Commission of China, Southwest Minzu University, Chengdu, 610041, China.
| | - Hui Diao
- Livestock and Poultry Biological Products Key Laboratory of Sichuan Province, Sichuan Animtche Group Co. Ltd, Chengdu, 610066, China
| | - Qingtao Long
- College of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu, 610041, China
| | - Fang Gan
- College of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu, 610041, China
| | - Yi Mao
- College of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu, 610041, China
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12
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Banerjee T, Sarkar A, Ali SZ, Bhowmik R, Karmakar S, Halder AK, Ghosh N. Bioprotective Role of Phytocompounds Against the Pathogenesis of Non-alcoholic Fatty Liver Disease to Non-alcoholic Steatohepatitis: Unravelling Underlying Molecular Mechanisms. PLANTA MEDICA 2024; 90:675-707. [PMID: 38458248 DOI: 10.1055/a-2277-4805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/10/2024]
Abstract
Non-alcoholic fatty liver disease (NAFLD), with a global prevalence of 25%, continues to escalate, creating noteworthy concerns towards the global health burden. NAFLD causes triglycerides and free fatty acids to build up in the liver. The excessive fat build-up causes inflammation and damages the healthy hepatocytes, leading to non-alcoholic steatohepatitis (NASH). Dietary habits, obesity, insulin resistance, type 2 diabetes, and dyslipidemia influence NAFLD progression. The disease burden is complicated due to the paucity of therapeutic interventions. Obeticholic acid is the only approved therapeutic agent for NAFLD. With more scientific enterprise being directed towards the understanding of the underlying mechanisms of NAFLD, novel targets like lipid synthase, farnesoid X receptor signalling, peroxisome proliferator-activated receptors associated with inflammatory signalling, and hepatocellular injury have played a crucial role in the progression of NAFLD to NASH. Phytocompounds have shown promising results in modulating hepatic lipid metabolism and de novo lipogenesis, suggesting their possible role in managing NAFLD. This review discusses the ameliorative role of different classes of phytochemicals with molecular mechanisms in different cell lines and established animal models. These compounds may lead to the development of novel therapeutic strategies for NAFLD progression to NASH. This review also deliberates on phytomolecules undergoing clinical trials for effective management of NAFLD.
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Affiliation(s)
- Tanmoy Banerjee
- Department of Pharmaceutical Technology, Jadavpur University, West Bengal, Kolkata, India
| | - Arnab Sarkar
- Department of Pharmaceutical Technology, Jadavpur University, West Bengal, Kolkata, India
| | - Sk Zeeshan Ali
- Department of Pharmaceutical Technology, Jadavpur University, West Bengal, Kolkata, India
| | - Rudranil Bhowmik
- Department of Pharmaceutical Technology, Jadavpur University, West Bengal, Kolkata, India
| | - Sanmoy Karmakar
- Department of Pharmaceutical Technology, Jadavpur University, West Bengal, Kolkata, India
| | - Amit Kumar Halder
- Dr. B. C. Roy College of Pharmacy and Allied Health Sciences, Dr. Meghnad Saha Sarani, Bidhannagar, Durgapur, West Bengal, India
| | - Nilanjan Ghosh
- Department of Pharmaceutical Technology, Jadavpur University, West Bengal, Kolkata, India
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13
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Evans WA, Eccles-Miller JA, Anderson E, Farrell H, Baldwin WS. 9-HODE and 9-HOTrE alter mitochondrial metabolism, increase triglycerides, and perturb fatty acid uptake and synthesis associated gene expression in HepG2 cells. Prostaglandins Leukot Essent Fatty Acids 2024; 202:102635. [PMID: 39142221 PMCID: PMC11404490 DOI: 10.1016/j.plefa.2024.102635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 07/17/2024] [Accepted: 08/06/2024] [Indexed: 08/16/2024]
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) prevalence is rising and can lead to detrimental health outcomes such as Non-Alcoholic Steatohepatitis (NASH), cirrhosis, and cancer. Recent studies have indicated that Cytochrome P450 2B6 (CYP2B6) is an anti-obesity CYP in humans and mice. Cyp2b-null mice are diet-induced obese, and human CYP2B6-transgenic (hCYP2B6-Tg) mice reverse the obesity or diabetes progression, but with increased liver triglyceride accumulation in association with an increase of several oxylipins. Notably, 9-hydroxyoctadecadienoic acid (9-HODE) produced from linoleic acid (LA, 18:2, ω-6) is the most prominent of these and 9-hydroxyoctadecatrienoic acid (9-HOTrE) from alpha-linolenic acid (ALA, 18:3, ω-3) is the most preferentially produced when controlling for substrate concentrations in vitro. Transactivation assays indicate that 9-HODE and 9-HOTrE activate PPARα and PPARγ. In Seahorse assays performed in HepG2 cells, 9-HOTrE increased spare respiratory capacity, slightly decreased palmitate metabolism, and increased non-glycolytic acidification in a manner consistent with slightly increased glutamine utilization; however, 9-HODE exhibited no effect on metabolism. Both compounds increased triglyceride and pyruvate concentrations, most strongly by 9-HOTrE, consistent with increased spare respiratory capacity. qPCR analysis revealed several perturbations in fatty acid uptake and metabolism gene expression. 9-HODE increased expression of CD36, FASN, PPARγ, and FoxA2 that are involved in lipid uptake and production. 9-HOTrE decreased ANGPTL4 expression and increased FASN expression consistent with increased fatty acid uptake, fatty acid production, and AMPK activation. Our findings support the hypothesis that 9-HODE and 9-HOTrE promote steatosis, but through different mechanisms as 9-HODE is directly involved in fatty acid uptake and synthesis; 9-HOTrE weakly inhibits mitochondrial fatty acid metabolism while increasing glutamine use.
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Affiliation(s)
- William A Evans
- Clemson University, Biological Sciences, Clemson, SC 29634, USA
| | | | | | - Hannah Farrell
- Clemson University, Biological Sciences, Clemson, SC 29634, USA
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14
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Fan S, Zhou Y, Zhao Y, Daglia M, Zhang J, Zhu Y, Bai J, Zhu L, Xiao X. Metabolomics reveals the effects of Lactiplantibacillus plantarum dy-1 fermentation on the lipid-lowering capacity of barley β-glucans in an in vitro model of gut-liver axis. Int J Biol Macromol 2023; 253:126861. [PMID: 37714241 DOI: 10.1016/j.ijbiomac.2023.126861] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 07/11/2023] [Accepted: 09/09/2023] [Indexed: 09/17/2023]
Abstract
Bioactive polysaccharides known as the biological response modifiers, can directly interact with intestinal epithelium cells (IEC) and regulate key metabolic processes such as lipid metabolism. Here, the coculture of Caco-2/HT29 monolayer (>400 Ω × cm2) and HepG2 cells was developed to mimic the gut-liver interactions. This system was used to investigate the effects of raw and fermented barley β-glucans (RBG and FBG) on lipid metabolism by directly interacting with IEC. Both RBG and FBG significantly and consistently reduced the lipid droplets and triacylglycerol levels in monoculture and coculture of HepG2 overloaded with oleic acid. Notably, FBG significantly and distinctly elevated PPARα (p < 0.05) and PPARα-responsive ACOX-1 (p < 0.01) gene expressions, promoting lipid degradation in cocultured HepG2. Moreover, the metabolomics analyses revealed that FBG had a unique impact on extracellular metabolites, among them, the differential metabolite thiomorpholine 3-carboxylate was significantly and strongly correlated with PPARα (r = -0.68, p < 0.01) and ACOX-1 (r = -0.76, p < 0.01) expression levels. Taken together, our findings suggest that FBG-mediated gut-liver interactions play a key role in its lipid-lowering effects that are superior to those of RBG. These results support the application of Lactiplantibacillus fermentation for improving hypolipidemic outcomes.
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Affiliation(s)
- Songtao Fan
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China
| | - Yurong Zhou
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China
| | - Yansheng Zhao
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China
| | - Maria Daglia
- Department of Pharmacy, University of Naples Federico II, Naples, Italy; International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, China
| | - Jiayan Zhang
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China
| | - Ying Zhu
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China
| | - Juan Bai
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China
| | - Lin Zhu
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China
| | - Xiang Xiao
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China.
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15
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Zeng T, Song Y, Qi S, Zhang R, Xu L, Xiao P. A comprehensive review of vine tea: Origin, research on Materia Medica, phytochemistry and pharmacology. JOURNAL OF ETHNOPHARMACOLOGY 2023; 317:116788. [PMID: 37343650 DOI: 10.1016/j.jep.2023.116788] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 05/24/2023] [Accepted: 06/13/2023] [Indexed: 06/23/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Vine tea is a popular folk tea that has been consumed in China for more than 1200 years. It is often used in ethnic medicine by ethnic groups in southwest China with at least 35 aliases in 10 provinces. In coastal areas, vine tea is mostly used to treat heatstroke, aphtha, aphonia, toothache, etc. In contrast, in the southwest inland regions, vine tea is mostly used to clear away heat and toxic materials, antiphlogosis and relieving sore-throat, lowering blood pressure and lipid levels, and alleviating fatigue. Three main species have been used as the source of vine tea, Nekemias grossedentata, Nekemias cantonensis and Nekemias megalophylla. Among them, the leaves of Nekemias grossedentata were considered as new food resource in complicance with regulations, according to the Food Safety Standards published by the Monitoring and Evaluation Department of the National Health and Family Planning Commission in China. AIM OF THE STUDY At present, the comprehensively summary of Materia Medica on the history and source of vine tea is currently unavailable. The current article summed up the Materia Medica, species origin and pharmacological effects of all 3 major species used in vine tea to fill the knowledge gaps. We also aim to provide a reference for future research on historical textual, resource development and medicinal utilization of vine tea. MATERIALS AND METHODS Adhering to the literature screening methodology outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this review encompasses 148 scholarly research papers from three database, paper ancient books, local chronicles and folklore through field investigations. We then comprehensively summarized and discussed research progresses in scientific and application studies of vine tea. RESULTS The historical records indicated that vine tea could have been used as early as Southern and Northern Dynasties (AC 420-589). Nekemias grossedentata, Nekemias cantonensis and Nekemias megalophylla, were used to considered as vine tea in the ethnic medicine. The main phytochemicals found in three plants are flavonoids, polyphenols and terpenoids, among which dihydromyricetin (DHM) is the most important and most studied active substance. The key words "Ampelopsis grossedentata" (Synonym of Nekemias grossedentata) and "dihydromyricetin/DHM" showed the highest frequency over the last 27 year based on the research trend analysis. And the ethnopharmacology studies drawn the main activities of vine tea are antioxidant, antibacterial, hepatoprotective, neuroprotective and anti-atherosclerosis activities. CONCLUSIONS This review systematically summarized and discussed vine tea from the following five aspects, history, genetic relationship, phytochemistry, research trend and ethnopharmacology. Vine tea has a long historical usage in Chinese ethnic medicine. Its outstanding therapeutic efficacies have attracted extensive attention in other places in the world at present. Nekemias cantonensis and Nekemias megalophylla are quite similar to Nekemias grossedentata in terms of many aspects. However, the current research has a narrow focus on mainly Nekemias grossedentata and DHM. We propose that future studies could be carried out to determine the synergistic effect of multi-components and multi-targets of vine tea including all 3 species to provide valuable knowledge.
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Affiliation(s)
- Tiexin Zeng
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
| | - Yanjun Song
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
| | - Shunyao Qi
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
| | - Ruyue Zhang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
| | - Lijia Xu
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
| | - Peigen Xiao
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
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16
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Liu Z, Wang W, Li X, Zhao J, Zhu H, Que S, He Y, Xu J, Zhou L, Mardinoglu A, Zheng S. Multi-omics network analysis on samples from sequential biopsies reveals vital role of proliferation arrest for Macrosteatosis related graft failure in rats after liver transplantation. Genomics 2023; 115:110748. [PMID: 37984718 DOI: 10.1016/j.ygeno.2023.110748] [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: 06/12/2023] [Revised: 10/12/2023] [Accepted: 11/15/2023] [Indexed: 11/22/2023]
Abstract
To investigate the molecular impact of graft MaS on post-transplant prognosis, based on multi-omics integrative analysis. Rats were fed by methionine-choline deficient diet (MCD) for MaS grafts. Samples were collected from grafts by sequential biopsies. Transcriptomic and metabolomic profilings were assayed. Post-transplant MaS status showed a close association with graft failure. Differentially expressed genes (DEGs) for in-vivo MaS were mainly enriched on pathways of cell cycle and DNA replication. Post-transplant MaS caused arrests of graft regeneration via inhibiting the E2F1 centered network, which was confirmed by an in vitro experiment. Data from metabolomics assays found insufficient serine/creatine which is located on one‑carbon metabolism was responsible for MaS-related GF. Pre-transplant MaS caused severe fibrosis in long-term survivors. DEGs for grafts from long-term survivors with pre-transplant MaS were mainly enriched in pathways of ECM-receptor interaction and focal adhesion. Transcriptional regulatory network analysis confirmed SOX9 as a key transcription factor (TF) for MaS-related fibrosis. Metabolomic assays found elevation of aromatic amino acid (AAA) was a major feature of fibrosis in long-term survivors. Graft MaS in vivo increased post-transplant GF via negative regulations on graft regeneration. Pre-transplant MaS induced severe fibrosis in long-term survivors via activations on ECM-receptor interaction and AAA metabolism.
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Affiliation(s)
- Zhengtao Liu
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, Zhejiang, China; NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Shulan Hospital (Hangzhou), Hangzhou 310 000, China.
| | - Wenchao Wang
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Xiang Li
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Junsheng Zhao
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, Zhejiang, China
| | - Hai Zhu
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | | | - Yong He
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jun Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Lin Zhou
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Adil Mardinoglu
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 9RT, UK; Science for Life Laboratory, KTH-Royal Institute of Technology, SE-17121 Stockholm, Sweden.
| | - Shusen Zheng
- Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, Zhejiang, China; NHC Key Laboratory of Combined Multi-Organ Transplantation, Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Shulan Hospital (Hangzhou), Hangzhou 310 000, China; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
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17
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Ren X, Yuan P, Niu J, Liu Y, Li Y, Huang L, Jiang S, Jiao N, Yuan X, Li J, Yang W. Effects of dietary supplementation with microencapsulated Galla chinensis tannins on growth performance, antioxidant capacity, and lipid metabolism of young broiler chickens. Front Vet Sci 2023; 10:1259142. [PMID: 37954663 PMCID: PMC10637619 DOI: 10.3389/fvets.2023.1259142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 10/16/2023] [Indexed: 11/14/2023] Open
Abstract
This study aimed to investigate the impacts of dietary supplementation with Galla chinensis tannins (GCT) on the growth performance, antioxidant capacity, and lipid metabolism of young broilers. Overall, a total of 216 healthy 1 day-old broilers were randomly allocated to CON group and GCT group, and provided with a basal diet or a basal diet added with 300 mg/kg microencapsulated GCT, respectively, in a 21 days trial. Our findings indicated that dietary GCT addition had no significant effects (p > 0.05) on growth performance. However, GCT supplementation led to a significant reduction in the total cholesterol (TC) concentration in the serum and liver (p < 0.05). Furthermore, GCT supplementation significantly increased the ratios of high-density lipoprotein (HDL) to low-density lipoprotein (LDL) and HDL to TC in the serum, in addition to elevating the activities of enzymes related to lipid metabolism in the liver (p < 0.05). Dietary GCT addition also improved the antioxidant capacity of the broilers, as evidenced by a significant decrease in the concentration of malondialdehyde in serum and liver (p < 0.05). Additionally, the GCT group exhibited significantly increased expressions of hepatic genes associated with antioxidant enzymes (HO-1, GPX1, SOD2, SIRT1, CPT-1, and PPARα) (p < 0.05), while the mRNA expression of SREBP-1 was significantly decreased (p < 0.05) compared with the CON group. In conclusion, dietary addition of 300 mg/kg microencapsulated GCT improved the antioxidant status and lipid metabolism of broilers without affecting their growth performance.
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Affiliation(s)
- Xiaojie Ren
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an, China
- Shandong Taishan Shengliyuan Group Co., Ltd, Tai’an, China
| | - Peng Yuan
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an, China
| | - Jiaxing Niu
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an, China
| | - Yang Liu
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an, China
| | - Yang Li
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an, China
- Division of Animal and Human Health Engineering, Department of Biosystems, KU Leuven, Heverlee, Belgium
| | - Libo Huang
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an, China
| | - Shuzhen Jiang
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an, China
| | - Ning Jiao
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an, China
| | - Xuejun Yuan
- College of Life Sciences, Shandong Agricultural University, Tai’an, China
| | - Junxun Li
- Shandong Taishan Shengliyuan Group Co., Ltd, Tai’an, China
| | - Weiren Yang
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Department of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an, China
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18
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Wu M, Wang Q, Zhang H, Pan Z, Zeng Q, Fang W, Mao J, Li J, Wu H, Qiu Z. Performance and mechanism of co-culture of Monascus purpureus, Lacticaseibacillus casei, and Saccharomyces cerevisiae to enhance lovastatin production and lipid-lowering effects. Bioprocess Biosyst Eng 2023; 46:1411-1426. [PMID: 37688635 DOI: 10.1007/s00449-023-02903-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 07/04/2023] [Indexed: 09/11/2023]
Abstract
To facilitate lipid-lowering effects, a lovastatin-producing microbial co-culture system (LPMCS) was constituted with a novel strain Monascus purpureus R5 in combination with Lacticaseibacillus casei S5 and Saccharomyces cerevisiae J7, which increased lovastatin production by 54.21% compared with the single strain R5. Response Surface Methodology (RSM) optimization indicated lovastatin yield peaked at 7.43 mg/g with a fermentation time of 13.88 d, water content of 50.5%, and inoculum ratio of 10.27%. Meanwhile, lovastatin in LPMCS co-fermentation extracts (LFE) was qualitatively and quantitatively analyzed by Thin-Layer Chromatography (TLC) and High-Performance Liquid Chromatography (HPLC). Cellular experiments demonstrated that LFE exhibited no obvious cytotoxicity to L-02 cells and exhibited excellent biosafety. Most notably, high-dose LFE (100 mg/L) exhibited the highest reduction of lipid accumulation, total cholesterol, and triglycerides simultaneously in oleic acid-induced L-02 cells, which decreased by 71.59%, 38.64%, and 58.85% than untreated cells, respectively. Overall, LPMCS provides a potential approach to upgrade the lipid-lowering activity of Monascus-fermented products with higher health-beneficial effects.
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Affiliation(s)
- Minghui Wu
- School of Life Science and Engineering, Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, Southwest Jiaotong University, No. 111 Second Ring Road, Chengdu, 610031, Sichuan, People's Republic of China
| | - Qiqi Wang
- School of Life Science and Engineering, Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, Southwest Jiaotong University, No. 111 Second Ring Road, Chengdu, 610031, Sichuan, People's Republic of China
| | - Han Zhang
- School of Life Science and Engineering, Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, Southwest Jiaotong University, No. 111 Second Ring Road, Chengdu, 610031, Sichuan, People's Republic of China
| | - Zhengyong Pan
- School of Life Science and Engineering, Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, Southwest Jiaotong University, No. 111 Second Ring Road, Chengdu, 610031, Sichuan, People's Republic of China
| | - Qilu Zeng
- School of Life Science and Engineering, Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, Southwest Jiaotong University, No. 111 Second Ring Road, Chengdu, 610031, Sichuan, People's Republic of China
| | - Weizhen Fang
- Analysis & Testing Center, Southwest Jiaotong University, Chengdu, 610031, Sichuan, People's Republic of China
| | - Jilong Mao
- School of Life Science and Engineering, Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, Southwest Jiaotong University, No. 111 Second Ring Road, Chengdu, 610031, Sichuan, People's Republic of China
- Chengdu Nuohe Shengtai Biotechnology Co., Ltd, Chengdu, 610041, Sichuan, People's Republic of China
| | - Jianpeng Li
- School of Life Science and Engineering, Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, Southwest Jiaotong University, No. 111 Second Ring Road, Chengdu, 610031, Sichuan, People's Republic of China
| | - Han Wu
- School of Life Science and Engineering, Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, Southwest Jiaotong University, No. 111 Second Ring Road, Chengdu, 610031, Sichuan, People's Republic of China
| | - Zhongping Qiu
- School of Life Science and Engineering, Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, Southwest Jiaotong University, No. 111 Second Ring Road, Chengdu, 610031, Sichuan, People's Republic of China.
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Miao X, Luo P, Liu J, Wang J, Chen Y. Dihydromyricetin ameliorated nonalcoholic steatohepatitis in mice by regulating the composition of serous lipids, bile acids and ileal microflora. Lipids Health Dis 2023; 22:112. [PMID: 37533083 PMCID: PMC10394885 DOI: 10.1186/s12944-023-01871-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 07/07/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Dihydromyricetin (DMY) is a natural flavonoid with anti-nonalcoholic steatohepatitis (NASH) activity. However, the effects of DMY on the composition of lipids and bile acids (BAs) in serum, and gut microbiota (GM) in ileum of mice with NASH are not clear. METHODS After male C57BL/6 mice was fed with methionine and choline deficiency (MCD) diet and simultaneously administered with DMY (300 mg/kg/day) by gavage for 8 weeks, the pathological changes of liver tissue were observed by Oil Red O, hematoxylin eosin and Masson staining, the levels of serum alaninea minotransferase, aspartate aminotransferase and liver triglyceride, malonic dialdehyde were detected by the detection kits, the composition and contents of serum lipids and BAs were detected by Liquid Chromatograph-Mass Spectrometry, the mRNA levels of hepatic BAs homeostasis-related genes were detected by RT-qPCR, and microbiological diversity in ileum was analyzed by 16S rDNA sequencing. RESULTS The results showed that the significant changes including 29 lipids, 4 BAs (23-nor-deoxycholic acid, ursodeoxycholic acid, 7-ketodeoxycholic acid and cholic acid), 2 BA transporters (Mrp2 and Oatp1b2) and 8 GMs between MCD and DMY groups. Among them, DMY treatment significantly down-regulated 21 lipids, 4 BAs mentioned above, the ratio of Firmicutes/Bacteroidota and the abundance of Erysipelotrichaceae, Faecalibacuium, significantly up-regulated 8 lipids and 5 GMs (Verrucomicrobiota, Bacteroidota, Actinobacteria, Akkermansiaceae and Akkermansia). CONCLUSIONS The results suggested that DMY may alleviate MCD diet-induced NASH through decreasing the serum levels of toxic BAs which regulated by liver Oatp1b2 and Mrp2, regulating the metabolism of related lipids, and up-regulating intestinal probiotics (Actinobacteria and Verrucomicrobiota at the phylum level; Akkermansiaceae at the family level; Akkermansiaat at the genus level) and inhibiting intestinal harmful bacteria (Firmicutes at the phylum level; Erysipelotrichaceae at the family level; Faecalibaculum at the genus level).
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Affiliation(s)
- Xiaolei Miao
- Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei University, Wuhan, 430062, China
- School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, China
| | - Ping Luo
- School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, China
| | - Jiao Liu
- Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei University, Wuhan, 430062, China
| | - Junjun Wang
- Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei University, Wuhan, 430062, China.
| | - Yong Chen
- Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei University, Wuhan, 430062, China.
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20
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Nie H, Ji T, Fu Y, Chen D, Tang Z, Zhang C. Molecular mechanisms and promising role of dihydromyricetin in cardiovascular diseases. Physiol Res 2022. [DOI: 10.33549/physiolres.934915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Vine tea, a Chinese herbal medicine, is widely used in traditional Asian medicine to treat common health problems. Dihydromyricetin (DMY) is the main functional flavonoid compound extracted from vine tea. In recent years, preclinical studies have focused on the potential beneficial effects of dihydromyricetin, including glucose metabolism regulation, lipid metabolism regulation, neuroprotection, and anti-tumor effects. In addition, DMY may play a role in cardiovascular disease by resisting oxidative stress and participating in the regulation of inflammation. This review is the first review that summaries the applications of dihydromyricetin in cardiovascular diseases, including atherosclerosis, myocardial infarction, myocardial hypertrophy, and diabetic cardiomyopathy. We also clarified the underlying mechanisms and signaling pathways involved in the above process. The aim of this review is to provide a better understanding and quick overview for future researches of dihydromyricetin in the field of cardiovascular diseases, and more detailed and robust researches are needed for evaluation and reference.
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Affiliation(s)
| | | | | | | | | | - C Zhang
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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21
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Liang M, Huo M, Guo Y, Zhang Y, Xiao X, Xv J, Fang L, Li T, Wang H, Dong S, Jiang X, Yu W. Aqueous extract of Artemisia capillaris improves non-alcoholic fatty liver and obesity in mice induced by high-fat diet. Front Pharmacol 2022; 13:1084435. [PMID: 36518663 PMCID: PMC9742474 DOI: 10.3389/fphar.2022.1084435] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Accepted: 11/15/2022] [Indexed: 01/21/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and is a nutritional metabolic disease. Artemisia capillaris (AC) is the above-ground dried part of Artemisia capillaris Thunb. or Artemisia scoparia Waldst. et Kit., a natural medicinal plant with pharmacological effects of heat-clearing and biliary-promoting. In order to evaluate the therapeutic effect of Artemisia capillaris on NAFLD and obesity, experiments were conducted using aqueous extracts of Artemisia capillaris (WAC) to intervene in NAFLD models in vivo and in vitro. In vivo experiments were performed using HFD-fed (high fat diet) C57BL/6 mice to induce NAFLD model, and in vitro experiments were performed using oleic acid to induce HepG2 cells to construct NAFLD cell model. H.E. staining and oil red O staining of liver tissue were used to observe hepatocytes. Blood biochemistry analyzer was used to detect serum lipid levels in mice. The drug targets and mechanism of action of AC to improve NAFLD were investigated by western blotting, qRT-PCR and immunofluorescence. The results showed that C57BL/6 mice fed HFD continuously for 16 weeks met the criteria for NAFLD in terms of lipid index and hepatocyte fat accumulation. WAC was able to reverse the elevation of serum lipid levels induced by high-fat diet in mice. WAC promoted the phosphorylation levels of PI3K/AKT and AMPK in liver and HepG2 cells of NAFLD mice, inhibited SREBP-1c expression, reduced TG and lipogenesis, and decreased lipid accumulation. In summary, WAC extract activates PI3K/AKT pathway, reduces SREBP-1c protein expression by promoting AMPK phosphorylation, and decreases fatty acid synthesis and TG content in hepatocytes. AC can be used as a potential health herb to improve NAFLD and obesity.
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Affiliation(s)
- Meng Liang
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Mohan Huo
- Department of Life Sciences, Northeast Agricultural University, Harbin, China
| | - Yi Guo
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Yuyi Zhang
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Xiao Xiao
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Jianwen Xv
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Lixue Fang
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Tianqi Li
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Huan Wang
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Siyu Dong
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Xiaowen Jiang
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, China
| | - Wenhui Yu
- Department of Veterinary Medicine, Northeast Agricultural University, Harbin, China
- Institute of Chinese Veterinary Medicine, Northeast Agricultural University, Harbin, China
- Heilongjiang Provincial Key Laboratory for Prevention and Control of Common Animal Diseases, Northeast Agricultural University, Harbin, China
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22
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Molecular mechanism and therapeutic significance of dihydromyricetin in nonalcoholic fatty liver disease. Eur J Pharmacol 2022; 935:175325. [PMID: 36265611 DOI: 10.1016/j.ejphar.2022.175325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 10/04/2022] [Accepted: 10/11/2022] [Indexed: 11/17/2022]
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23
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Lu Z, Sun GF, Pan XA, Qu XH, Yang P, Chen ZP, Han XJ, Wang T. BCATc inhibitor 2 ameliorated mitochondrial dysfunction and apoptosis in oleic acid-induced non-alcoholic fatty liver disease model. Front Pharmacol 2022; 13:1025551. [PMID: 36386234 PMCID: PMC9650408 DOI: 10.3389/fphar.2022.1025551] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 10/18/2022] [Indexed: 09/14/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a prevalent hepatic disease in the world. Disorders of branched chain amino acid (BCAA) metabolism is involved in various diseases. In this study, we aim to explore the role of BCAA metabolism in the development of NAFLD and the protective effect of BCATc Inhibitor 2, an inhibitor of cytosolic branched chain amino acid transaminase, against NAFLD as well as its underlying mechanism. It was found that oleic acid induced lipid accumulation and apoptosis in HepG2 and LO2 cells. Supplementation of BCAAs further aggravated oleic acid-induced lipid accumulation and apoptosis. In contrast, treatment of BCATc Inhibitor 2 ameliorated oleic acid-induced lipid accumulation and apoptosis. Molecularly, supplementation of BCAAs or treatment of BCATc Inhibitor 2 up-regulated or down-regulated the expression of SREBP1 and lipogenesis-related genes without affecting lipolysis-related genes. BCATc Inhibitor 2 maintained mitochondrial function by ameliorating oleic acid-induced mitochondrial ROS generation and mitochondrial membrane potential disruption. In addition, BCATc Inhibitor 2 treatment alleviated oleic acid-induced activation of JNK and AKT signaling pathway and Bcl2/Bax/Caspase axis. In conclusion, our results indicate BCAA metabolism is involved in NAFLD and BCATc Inhibitor 2 protects against oleic acid-induced lipid accumulation and apoptosis. These findings suggest that BCATc Inhibitor 2 is a promising candidate drug for the treatment of NAFLD.
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Affiliation(s)
- Zhuo Lu
- Institute of Geriatrics, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
- Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Gui-Feng Sun
- Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, China
| | - Xiao-An Pan
- Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, China
| | - Xin-Hui Qu
- Institute of Geriatrics, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
- Department of Neurology, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Ping Yang
- Department of Neurology, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Zhi-Ping Chen
- Department of Critical Care Medicine, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Xiao-Jian Han
- Institute of Geriatrics, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
- Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, China
- Department of Neurology, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Tao Wang
- Institute of Geriatrics, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
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24
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Protective effects of monoammonium glycyrrhizinate on fatty deposit degeneration induced in primary calf hepatocytes by sodium oleate administration in vitro. Res Vet Sci 2022; 150:213-223. [DOI: 10.1016/j.rvsc.2022.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 04/20/2022] [Accepted: 05/04/2022] [Indexed: 11/20/2022]
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25
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Zhang C, Meng S, Li C, Yang Z, Wang G, Wang X, Ma Y. Primary Broiler Hepatocytes for Establishment of a Steatosis Model. Vet Sci 2022; 9:vetsci9070316. [PMID: 35878333 PMCID: PMC9319065 DOI: 10.3390/vetsci9070316] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 06/17/2022] [Accepted: 06/20/2022] [Indexed: 11/19/2022] Open
Abstract
Fatty liver hemorrhage syndrome (FLHS) in chickens is characterized by steatosis and bleeding in the liver, which has caused huge losses to the poultry industry. This study aimed to use primary cultured broiler hepatocytes to establish a steatosis model to explore the optimal conditions for inducing steatosis by incubating the cells with a fat emulsion. Primary hepatocytes were isolated from an AA broiler by a modified two-step in situ perfusion method. Hepatocytes were divided into an untreated control group and a fat emulsion group that was incubated with 2.5, 5, 10, or 20% fat emulsion for different times to determine the optimal conditions for inducing steatosis of primary hepatocytes. Incubation of the cells with 10% fat emulsion resulted in cell viability at 48 h of 67%, which was higher than the control group and met the requirements of the model. In the second experiment, steatosis was induced by incubating hepatocytes with 10% fat emulsion for 48 h. In consequence, the apoptosis rate decreased (p > 0.05) and the concentration of ALT (p < 0.001), AST (p < 0.01), and TG (p < 0.05) increased significantly; the expression level of SREBP-1c (p < 0.05) increased, and the expression levels of PPARα (p < 0.001), CPT1 (p < 0.001), and CPT2 (p < 0.05) were lower in the fat emulsion group than in the control group. In conclusion, the induction condition was selected as 10% fat emulsion incubation for 48 h, and we successfully established a fatty liver degeneration model for broilers.
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26
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Lin HH, Hsu JY, Tseng CY, Huang XY, Tseng HC, Chen JH. Hepatoprotective Activity of Nelumbo nucifera Gaertn. Seedpod Extract Attenuated Acetaminophen-Induced Hepatotoxicity. Molecules 2022; 27:molecules27134030. [PMID: 35807275 PMCID: PMC9268144 DOI: 10.3390/molecules27134030] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 06/18/2022] [Accepted: 06/21/2022] [Indexed: 01/27/2023] Open
Abstract
The aim is to investigate the effect of lotus (Nelumbo nucifera Gaertn.) seedpod extract (LSE) on acetaminophen (APAP)-induced hepatotoxicity. LSE is rich in polyphenols and has potent antioxidant capacity. APAP is a commonly used analgesic, while APAP overdose is the main reason for drug toxicity in the liver. Until now, there has been no in vitro test of LSE in drug-induced hepatotoxicity responses. LSEs were used to evaluate the effect on APAP-induced cytotoxicity, ROS level, apoptotic rate, and molecule mechanisms. The co-treatment of APAP and LSEs elevated the survival rate and decreased intracellular ROS levels on HepG2 cells. LSEs treatment could significantly reduce APAP-induced HepG2 apoptosis assessed by DAPI and Annexin V/PI. The further molecule mechanisms indicated that LSEs decreased Fas/FasL binding and reduced Bax and tBid to restore mitochondrial structure and subsequently suppress downstream apoptosis cascade activation. These declines in COX-2, NF-κB, and iNOS levels were observed in co-treatment APAP and LSEs, which indicated that LSEs could ameliorate APAP-induced inflammation. LSE protected APAP-induced apoptosis by preventing extrinsic, intrinsic, and JNK-mediated pathways. In addition, the restoration of mitochondria and inflammatory suppression in LSEs treatments indicated that LSEs could decrease oxidative stress induced by toxic APAP. Therefore, LSE could be a novel therapeutic option for an antidote against overdose of APAP.
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Affiliation(s)
- Hui-Hsuan Lin
- Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, Taiwan;
| | - Jen-Ying Hsu
- Department of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan; (J.-Y.H.); (C.-Y.T.); (X.-Y.H.)
| | - Chiao-Yun Tseng
- Department of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan; (J.-Y.H.); (C.-Y.T.); (X.-Y.H.)
| | - Xiao-Yin Huang
- Department of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan; (J.-Y.H.); (C.-Y.T.); (X.-Y.H.)
| | - Hsien-Chun Tseng
- Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan
- Department of Radiation Oncology, School of Medicine, Chung Shan Medical University, Taichung City 40201, Taiwan
- Correspondence: (H.-C.T.); (J.-H.C.); Tel.: +886-4-24730022 (ext. 12195) (J.-H.C.); Fax: +886-4-23248175 (J.-H.C.)
| | - Jing-Hsien Chen
- Department of Nutrition, Chung Shan Medical University, Taichung City 40201, Taiwan; (J.-Y.H.); (C.-Y.T.); (X.-Y.H.)
- Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan
- Correspondence: (H.-C.T.); (J.-H.C.); Tel.: +886-4-24730022 (ext. 12195) (J.-H.C.); Fax: +886-4-23248175 (J.-H.C.)
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27
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Zhang HL, Wang ML, Yi LZ, Högger P, Arroo R, Bajpai VK, Prieto MA, Chen XJ, Simal-Gandara J, Cao H. Stability profiling and degradation products of dihydromyricetin in Dulbecco's modified eagle's medium. Food Chem 2022; 378:132033. [PMID: 35033717 DOI: 10.1016/j.foodchem.2021.132033] [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: 06/08/2021] [Revised: 12/20/2021] [Accepted: 12/31/2021] [Indexed: 11/30/2022]
Abstract
Dihydromyricetin has shown many bioactivities in cell level. However, dihydromyricetin was found to be highly instable in cell culture medium DMEM. Here, the underlying degradation mechanism was investigated via UPLC-MS/MS analysis. Dihydromyricetin was mainly converted into its dimers and oxidized products. At lower temperature, dihydromyricetin in DMEM showed higher stability. Vitamin C increased the stability of dihydromyricetin in DMEM probably due to its high antioxidant potential.
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Affiliation(s)
- H L Zhang
- Institute of Chinese Medical Sciences, University of Macau, Macao, China.
| | - M L Wang
- Institute of Chinese Medical Sciences, University of Macau, Macao, China.
| | - L Z Yi
- Faculty of Agriculture and Food, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
| | - P Högger
- Institut für Pharmazie und Lebensmittelchemie, Universität Würzburg, 97074 Würzburg, Germany.
| | - R Arroo
- De Montfort University - Leicester School of Pharmacy, The Gateway, Leicester LE1 9BH, UK.
| | - V K Bajpai
- Department of Energy and Materials Engineering, Dongguk University-Seoul, 30 Pildong-ro 1-gil, Seoul 04620, Republic of Korea
| | - M A Prieto
- Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E-32004 Ourense, Spain.
| | - X J Chen
- Institute of Chinese Medical Sciences, University of Macau, Macao, China.
| | - J Simal-Gandara
- Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E-32004 Ourense, Spain.
| | - H Cao
- Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E-32004 Ourense, Spain; College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
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Chen H, Nie T, Zhang P, Ma J, Shan A. Hesperidin attenuates hepatic lipid accumulation in mice fed high-fat diet and oleic acid induced HepG2 via AMPK activation. Life Sci 2022; 296:120428. [PMID: 35218767 DOI: 10.1016/j.lfs.2022.120428] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 02/16/2022] [Accepted: 02/19/2022] [Indexed: 12/12/2022]
Abstract
AIMS In recent years, more and more people are suffering from lifestyle-related disease such as nonalcoholic fatty liver disease (NAFLD) because of unhealthy diet and lack of physical exercise. Hesperidin (HDN) is a flavonoid found in high concentrations in citrus fruits. In this study, we investigated the effect of HDN on NAFLD, providing information to develop dietary supplements for NAFLD treatment and prevention. MATERIALS AND METHODS Testing kits, hematoxylin-eosin staining, oil red O staining, western blot, immunofluorescence, cck-8 assay, and blood biochemical analysis were carried out during the experiments in vivo and in vitro. KEY FINDINGS The current study revealed that HDN significantly reduced liver index and serum lipid levels, and protected against liver steatosis and injury induced by HFD. In addition, HDN suppressed oil acid induced intracellular lipid accumulation in HepG2 cells. Moreover, HDN increased the expression level of pAMPK and downregulated SREBP-1C, ACC and FAS expression in vivo and in vitro. SIGNIFICANCE In summary, HDN attenuates lipid accumulation in vivo and in vitro via AMPK activation, suggesting that HDN may serve as a potential therapeutic agent for treating NAFLD.
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Affiliation(s)
- Hao Chen
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, PR China
| | - Tong Nie
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, PR China
| | - Penglu Zhang
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, PR China
| | - Jun Ma
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, PR China.
| | - Anshan Shan
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang, PR China.
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[Dihydromyricetin reduces lipid accumulation in LO2 cells via AMPK/mTOR-mediated lipophagy pathway and inhibits HepG2 cell proliferation in vitro]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2022; 42:518-527. [PMID: 35527487 PMCID: PMC9085583 DOI: 10.12122/j.issn.1673-4254.2022.04.07] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
OBJECTIVE To explore the mechanism underlying the hepatoprotective effect of dihydromyricetin (DMY) against lipid accumulation in light of the lipophagy pathway and the inhibitory effect of DMY on HepG2 cell proliferation. METHODS LO2 cells were cultured in the presence of 10% FBS for 24 h and treated with 100 μg/mL DMY, or exposed to 50% FBS for 24 h followed by treatment with 50, 100, or 200 μg/mL DMY; the cells in recovery group were cultured in 50% FBS for 24 h and then in 10% FBS for another 24 h. Oil red O staining was used to observe the accumulation of lipid droplets in the cells, and the levels of TC, TG, and LDL and activities of AST, ALT and LDH were measured. The expression of LC3 protein was detected using Western blotting. AO staining and transmission electron microscopy were used to determine the numbers of autophagolysosomes and autophagosomes, respectively. The formation of autophagosomes was observed with MDC staining, and the mRNA expression levels of LC3, ATG7, AMPK, mTOR, p62 and Beclin1 were determined with q-PCR. Flow cytometry was performed to analyze the effect of 50, 100, and 200 μg/mL DMY on cell cycle and apoptosis of HepG2 cells; DNA integrity in the treated cells was examined with cell DNA fragmentation test. RESULTS DMY treatment and pretreatment obviously inhibited lipid accumulation and reduced the levels of TC, TG, LDL and enzyme activities of AST, ALT and LDH in LO2 cells (P < 0.05). In routinely cultured LO2 cells, DMY significantly promoted the formation of autophagosomes and autophagolysosomes and upregulated the expression of LC3 protein. DMY obviously attenuated high FBS-induced inhibition of autophagosome formation in LO2 cells, up- regulated the mRNA levels of LC3, ATG7, Beclin1 and AMPK, and downregulated p62 and mTOR mRNA levels (P < 0.05 or 0.01). In HepG2 cells, DMY caused obvious cell cycle arrest, inhibited cell proliferation, and induced late apoptosis and DNA fragmentation. CONCLUSION DMY reduces lipid accumulation in LO2 cells by regulating the AMPK/ mTOR-mediated lipophagy pathway and inhibits the proliferation of HepG2 by causing cell cycle arrest and promoting apoptosis.
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Shi L, Karrar E, Liu R, Chang M, Wang X. Comparative effects of sesame lignans (sesamin, sesamolin, and sesamol) on oxidative stress and lipid metabolism in steatosis HepG2 cells. J Food Biochem 2022; 46:e14180. [PMID: 35396857 DOI: 10.1111/jfbc.14180] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 03/19/2022] [Accepted: 03/24/2022] [Indexed: 12/17/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) can be attributed to the imbalance between lipogenesis and lipidolysis in the liver. Sesame lignans (sesamin, sesamolin, and sesamol) are unique bioactive compounds responsible for the nutritional function of sesame oils. However, the preventive effects of three lignans on oxidative stress and lipid metabolism in steatosis HepG2 cells have not been compared. In this study, we investigated the role of sesamin, sesamolin, and sesamol on hepatic lipid accumulation and explored the underlying mechanism via a well-established cell model. The results showed that 3 μg/ml of lignans could decrease the TG/TC contents and alleviate cellular oxidative stress, with an order of the lipid-lowering effect as sesamol > sesamin > sesamolin. The lignan-activated AMPK and PPAR signaling pathways enhanced gene and protein expressions related to fatty acid oxidation, cholesterol efflux, and catabolism. Meanwhile, treatment of the steatosis HepG2 cells with sesamin, sesamolin, and sesamol reduced lipid synthesis and cholesterol uptake, thus lowering intracellular lipogenesis in the process of NAFLD. Our data suggested that sesame lignans can attenuate oxidative stress and regulate lipid metabolism in liver cells, which may be potential therapeutic agents for treating the NAFLD. PRACTICAL APPLICATIONS: The present work demonstrated that sesame lignans can be used for dietary supplements or functional additives with excellent lipid-lowering effects. Furthermore, this study supplied potential molecular mechanisms involved in NAFLD treatment process, and also provided nutritional guidelines for sesame oil evaluation and selection.
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Affiliation(s)
- Longkai Shi
- National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Emad Karrar
- National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Ruijie Liu
- National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Ming Chang
- National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Xingguo Wang
- National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
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Guo Z, Chen X, Huang Z, Chen D, Yu B, He J, Yan H, Zheng P, Luo Y, Yu J, Chen H. Effect of dietary dihydromyricetin supplementation on lipid metabolism, antioxidant capacity and skeletal muscle fiber type transformation in mice. Anim Biotechnol 2021; 33:555-562. [PMID: 34866549 DOI: 10.1080/10495398.2021.2006204] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
This study aimed to investigate the effect of dietary dihydromyricetin (DHM) supplementation on lipid metabolism, antioxidant capacity and muscle fiber type transformation. Twenty-four male Kunming mice were randomly allotted to either control (basal diet) or DHM diets (supplemented with 300 mg/kg DHM). Our data showed that DHM administration decreased the triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) contents, and increased the catalase (CAT), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities in serum. In the liver, DHM decreased the TG and malondialdehyde (MDA) levels and increased the T-SOD and GSH-Px activities. For the tibialis anterior (TA) muscle, DHM increased the total antioxidant capacity (T-AOC) level and T-SOD activities. Western blotting and real-time quantitative PCR analysis showed that DHM increased the protein and mRNA levels of MyHC I and MyHC IIa and decreased the protein and mRNA levels of MyHC IIb in TA muscle, which may be achieved by activating the AMP-activated protein kinase (AMPK) signal. The mRNA levels of several regulatory factors related to mitochondrial function were up-regulated by DHM. In conclusion, dietary 300 mg/kg DHM supplementation improved lipid metabolism and antioxidant capacity and promoted the transformation of muscle fiber type from glycolysis to oxidation in mice.
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Affiliation(s)
- Zhongyang Guo
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Xiaoling Chen
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Zhiqing Huang
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Daiwen Chen
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Bing Yu
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Jun He
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Hui Yan
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Ping Zheng
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Yuheng Luo
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Jie Yu
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Hong Chen
- College of Food Science, Sichuan Agricultural University, Yaan, Sichuan, P. R. China
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Shi L, Karrar E, Wang X. Sesamol ameliorates hepatic lipid accumulation and oxidative stress in steatosis HepG2 cells via the PPAR signaling pathway. J Food Biochem 2021; 45:e13976. [PMID: 34664288 DOI: 10.1111/jfbc.13976] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 09/10/2021] [Accepted: 10/09/2021] [Indexed: 12/28/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic hepatopathy caused by disordered lipid metabolism in the liver. Sesamol, a phenolic compound derived from sesame oil, has been shown to inhibit obesity, hyperlipidemia, and atherosclerosis in previous investigations. However, the preventive effect of sesamol against hepatic steatosis and oxidative stress in NAFLD has not been well-studied. In this work, sesamol was observed to alleviate lipid accumulation and oxidative stress in high oleic acid (300 μM)/cholesterol (25 μM) induced HepG2 cells, thus indicating that sesamol was involved in regulating hepatic lipid metabolism and oxidative injury. Mechanism studies found that the activated peroxisome proliferator-activated receptors (PPAR) signaling pathway by sesamol intervention up-regulated gene and protein expressions related to fatty acid oxidation and cholesterol efflux and catabolism, thus accelerating lipid consumption and reducing intracellular lipid accumulation in the process of NAFLD. These data suggested that sesamol can effectively ameliorate hepatic steatosis and sesamol riched sesamol oil may be a potential agent for finding therapeutic strategies to treat the NAFLD. PRACTICAL APPLICATIONS: Sesamol and sesamol-rich sesame oil have received much attention due to their performance on hepatic lipid regulation. The results of this study indicate that sesamol treatment could ameliorate hepatic steatosis by inhibiting lipid accumulation and oxidative stress, thus demonstrating that sesamol and sesame oil can be used for functional foods and nutraceutical applications in the future. In addition, the present work provides knowledge of the effects of sesamol on NAFLD and involved mechanisms, and further supplies nutritional guidelines for sesame oil consumption.
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Affiliation(s)
- Longkai Shi
- National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Emad Karrar
- National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Xingguo Wang
- National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
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Kan J, Hui Y, Xie W, Chen C, Liu Y, Jin C. Lily bulbs' polyphenols extract ameliorates oxidative stress and lipid accumulation in vitro and in vivo. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2021; 101:5038-5048. [PMID: 33570774 DOI: 10.1002/jsfa.11148] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 02/04/2021] [Accepted: 02/11/2021] [Indexed: 06/12/2023]
Abstract
BACKGROUND Polyphenols have the potential to reduce the risk of many metabolic disorders. Lily bulbs are rich in polyphenols; however, their effects on lipid metabolism remain unclear. This study aimed to explore the effects of lily bulbs' polyphenols (LBPs) on oxidative stress and lipid metabolism. RESULTS A total of 14 polyphenolic compounds in LBPs were identified by high-performance liquid chromatography equipped with diode-array detection mass spectrometry. Total phenolic compound in LBPs was 53.76 ± 1.12 g kg-1 dry weight. In cellular experiments, LBPs attenuated the disruption of mitochondrial membrane potential, impeded reactive oxygen species production, alleviated oxidative stress, and reduced lipid accumulation in oleic acid induced HepG2 cells. In in vivo studies, LBPs significantly inhibited body weight gain, reduced lipid levels in serum and liver, and improved oxidative damage in a dose-dependent manner in mice fed a high-fat diet. Moreover, LBPs ameliorated hepatic steatosis and suppressed the expression of hepatic-lipogenesis-related genes (SREBP-1c, FAS, ACC1, and SCD-1) and promoted lipolysis genes (SRB1 and HL) and lipid oxidation genes (PPARα and CPT-1) in mice fed a high-fat diet. CONCLUSION It was concluded that LBPs are a potential complementary therapeutic alternative in the development of functional foods to curb obesity and obesity-related diseases, such as metabolic syndrome. © 2021 Society of Chemical Industry.
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Affiliation(s)
- Juan Kan
- College of Food Science and Engineering, Yangzhou University, Yangzhou, China
| | - Yaoyao Hui
- College of Food Science and Engineering, Yangzhou University, Yangzhou, China
| | - Wangjing Xie
- College of Food Science and Engineering, Yangzhou University, Yangzhou, China
| | - Cuicui Chen
- College of Food Science and Engineering, Yangzhou University, Yangzhou, China
| | - Ying Liu
- College of Food Science and Engineering, Yangzhou University, Yangzhou, China
| | - ChangHai Jin
- College of Food Science and Engineering, Yangzhou University, Yangzhou, China
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Fang W, Chen Q, Cui K, Chen Q, Li X, Xu N, Mai K, Ai Q. Lipid overload impairs hepatic VLDL secretion via oxidative stress-mediated PKCδ-HNF4α-MTP pathway in large yellow croaker (Larimichthys crocea). Free Radic Biol Med 2021; 172:213-225. [PMID: 34116177 DOI: 10.1016/j.freeradbiomed.2021.06.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 05/30/2021] [Accepted: 06/02/2021] [Indexed: 02/08/2023]
Abstract
Lipid overload-induced hepatic steatosis is a major public health problem worldwide. However, the potential molecular mechanism is not completely understood. Herein, we found that high-fat diet (HFD) or oleic acid (OA) treatment induced oxidative stress which prevented the entry of hepatocyte nuclear factor 4 alpha (HNF4α) into the nucleus by activating protein kinase C delta (PKCδ) in vivo and in vitro in large yellow croaker (Larimichthys crocea). This reduced the level of microsomal triglyceride transfer protein (MTP) transcription, resulting in the impaired secretion of very-low-density lipoprotein (VLDL) and the abnormal accumulation of triglyceride (TG) in hepatocytes. Meanwhile, the detrimental effects induced by lipid overload could be partly alleviated by pretreating hepatocytes with Go6983 (PKCδ inhibitor) or N-acetylcysteine (NAC, reactive oxygen species (ROS) scavenger). In conclusion, for the first time, we revealed that lipid overload impaired hepatic VLDL secretion via oxidative stress-mediated PKCδ-HNF4α-MTP pathway in fish. This study may provide critical insights into potential intervention strategies against lipid overload-induced hepatic steatosis of fish and human beings.
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Affiliation(s)
- Wei Fang
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, People's Republic of China
| | - Qiuchi Chen
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, People's Republic of China
| | - Kun Cui
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, People's Republic of China
| | - Qiang Chen
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, People's Republic of China
| | - Xueshan Li
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, People's Republic of China
| | - Ning Xu
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, People's Republic of China
| | - Kangsen Mai
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, People's Republic of China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, 266237, Qingdao, Shandong, People's Republic of China
| | - Qinghui Ai
- Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, People's Republic of China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, 266237, Qingdao, Shandong, People's Republic of China.
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Chen J, Wang X, Xia T, Bi Y, Liu B, Fu J, Zhu R. Molecular mechanisms and therapeutic implications of dihydromyricetin in liver disease. Biomed Pharmacother 2021; 142:111927. [PMID: 34339914 DOI: 10.1016/j.biopha.2021.111927] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 07/04/2021] [Accepted: 07/12/2021] [Indexed: 02/07/2023] Open
Abstract
Recent studies demonstrated that dihydromyricetin (DHM) has prominent therapeutic effects on liver injury and liver cancer. By summarizing the current preclinical in vitro and in vivo studies, the present review examines the preventive and therapeutic effects of DHM on liver disorders as well as its potential mechanisms. Briefly, in both chemical- and alcohol-induced liver injury models, DHM ameliorates hepatocyte necrosis and steatosis while promoting liver regeneration. In addition, DHM can alleviate nonalcoholic fatty liver disease (NAFLD) via regulating lipid/glucose metabolism, probably due to its anti-inflammatory or sirtuins-dependent mechanisms. Furthermore, DHM treatment inhibits cell proliferation, induces apoptosis and autophagy and regulates redox balance in liver cancer cells, thus exhibiting remarkable anti-cancer effects. The pharmacological mechanisms of DHM may be associated with its anti-inflammatory, anti-oxidative and apoptosis-regulatory benefits. With the accumulating interests in utilizing natural products to target common diseases, our work aims to improve the understanding of DHM acting as a novel drug candidate for liver diseases and to accelerate its translation from bench to bedside.
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Affiliation(s)
- Jingnan Chen
- The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, China; Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, China
| | - Xitong Wang
- The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, China; Laboratory of Hepatobiliary Surgery, The Affiliated Hospital of Guangdong Medical University, China
| | - Tian Xia
- The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, China; Laboratory of Hepatobiliary Surgery, The Affiliated Hospital of Guangdong Medical University, China
| | - Yanhua Bi
- The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, China
| | - Bin Liu
- Laboratory of Hepatobiliary Surgery, The Affiliated Hospital of Guangdong Medical University, China.
| | - Junfen Fu
- The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, China; Department of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, China.
| | - Runzhi Zhu
- The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, China; Laboratory of Hepatobiliary Surgery, The Affiliated Hospital of Guangdong Medical University, China; Cancer Center, Zhejiang University, China.
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Silva J, Carry E, Xue C, Zhang J, Liang J, Roberge JY, Davies DL. A Novel Dual Drug Approach That Combines Ivermectin and Dihydromyricetin (DHM) to Reduce Alcohol Drinking and Preference in Mice. Molecules 2021; 26:molecules26061791. [PMID: 33810134 PMCID: PMC8004700 DOI: 10.3390/molecules26061791] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/18/2021] [Accepted: 03/19/2021] [Indexed: 12/12/2022] Open
Abstract
Alcohol use disorder (AUD) affects over 18 million people in the US. Unfortunately, pharmacotherapies available for AUD have limited clinical success and are under prescribed. Previously, we established that avermectin compounds (ivermectin [IVM] and moxidectin) reduce alcohol (ethanol/EtOH) consumption in mice, but these effects are limited by P-glycoprotein (Pgp/ABCB1) efflux. The current study tested the hypothesis that dihydromyricetin (DHM), a natural product suggested to inhibit Pgp, will enhance IVM potency as measured by changes in EtOH consumption. Using a within-subjects study design and two-bottle choice study, we tested the combination of DHM (10 mg/kg; i.p.) and IVM (0.5–2.5 mg/kg; i.p.) on EtOH intake and preference in male and female C57BL/6J mice. We also conducted molecular modeling studies of DHM with the nucleotide-binding domain of human Pgp that identified key binding residues associated with Pgp inhibition. We found that DHM increased the potency of IVM in reducing EtOH consumption, resulting in significant effects at the 1.0 mg/kg dose. This combination supports our hypothesis that inhibiting Pgp improves the potency of IVM in reducing EtOH consumption. Collectively, we demonstrate the feasibility of this novel combinatorial approach in reducing EtOH consumption and illustrate the utility of DHM in a novel combinatorial approach.
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Affiliation(s)
- Joshua Silva
- Titus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA 90089, USA; (J.S.); (C.X.); (J.Z.); (J.L.)
| | - Eileen Carry
- Molecular Design and Synthesis Group, Rutgers University Biomedical Research Innovation Core, Piscataway, NJ 08854, USA; (E.C.); (J.Y.R.)
| | - Chen Xue
- Titus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA 90089, USA; (J.S.); (C.X.); (J.Z.); (J.L.)
| | - Jifeng Zhang
- Titus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA 90089, USA; (J.S.); (C.X.); (J.Z.); (J.L.)
| | - Jing Liang
- Titus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA 90089, USA; (J.S.); (C.X.); (J.Z.); (J.L.)
| | - Jacques Y. Roberge
- Molecular Design and Synthesis Group, Rutgers University Biomedical Research Innovation Core, Piscataway, NJ 08854, USA; (E.C.); (J.Y.R.)
| | - Daryl L. Davies
- Titus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA 90089, USA; (J.S.); (C.X.); (J.Z.); (J.L.)
- Correspondence: ; Tel.: +13-23-442-1427
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S-adenosylmethionine upregulates the angiotensin receptor-binding protein ATRAP via the methylation of HuR in NAFLD. Cell Death Dis 2021; 12:306. [PMID: 33753727 PMCID: PMC7985363 DOI: 10.1038/s41419-021-03591-1] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 03/01/2021] [Accepted: 03/03/2021] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has emerged globally and is associated with inflammatory signaling. The underlying mechanisms remain poorly delineated, although NAFLD has attracted considerable attention and been extensively investigated. Recent publications have determined that angiotensin II (Ang II) plays an important role in stimulating NAFLD progression by causing lipid metabolism disorder and insulin resistance through its main receptor, Ang II type 1 receptor (AT1R). Herein, we explored the effect of supplementary S-adenosylmethionine (SAM), which is the main biological methyl donor in mammalian cells, in regulating AT1R-associated protein (ATRAP), which is the negative regulator of AT1R. We found that SAM was depleted in NAFLD and that SAM supplementation ameliorated steatosis. In addition, in both high-fat diet-fed C57BL/6 rats and L02 cells treated with oleic acid (OA), ATRAP expression was downregulated at lower SAM concentrations. Mechanistically, we found that the subcellular localization of human antigen R (HuR) was determined by the SAM concentration due to protein methylation modification. Moreover, HuR was demonstrated to directly bind ATRAP mRNA and control its nucleocytoplasmic shuttling. Thus, SAM was suggested to upregulate ATRAP protein expression by maintaining the export of its mRNA from the nucleus. Taken together, our findings suggest that SAM can positively regulate ATRAP in NAFLD and may have various potential benefits for the treatment of NAFLD.
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Zhang X, Lu X, Zhou Y, Guo X, Chang Y. Major royal jelly proteins prevents NAFLD by improving mitochondrial function and lipid accumulation through activating the AMPK / SIRT3 pathway in vitro. J Food Sci 2021; 86:1105-1113. [PMID: 33580500 DOI: 10.1111/1750-3841.15625] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 12/29/2020] [Accepted: 01/11/2021] [Indexed: 11/28/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a metabolic syndrome, whose main characteristics are excessive lipid accumulation and oxidative stress. Major royal jelly proteins (MRJPs) is a kind of water-soluble protein, which is abundant in royal jelly (RJ). The aim of this study was to evaluate the effect of MRJPs on lipid accumulation and oxidative stress of liver cells. Here, we first optimized the conditions for extracting MRJPs from RJ and identified the extraction effect and product by SDS-PAGE. Then, we used oleic acid (OA) of 1.0 mM to induce hepatocytes for 24 hr to establish a stable cell models of lipid accumulation, and we found that pre-administration (24 hr) of MRJPs (0.2, 0.5, and 1.0 g/L) could significantly reduce the lipid drop content and triglyceride level in the model cells, and simultaneously reduce the alanine aminotransferase and aspertate aminotransferase levels in the cell culture supernatant. In addition, pre-incubation (24 hr) with MRJPs (0.2, 0.5, and 1.0 g/L) could restore superoxide dismutase (SOD) level and mitochondrial membrane potential as compared with OA group. Furthermore, MRJPs administration significantly upregulated the expression of Silent Information Regulator 2 Associated Protein 3, mitochondrial superoxide dismutase (SOD2), and cytochrome c oxidase subunit IV in OA-treated HepG2 cells. The study for the first time provides evidences on the lipid-lowering effect of MRJPs at the cellular level, which can further provide support for the development and application of polypeptide drugs in the future, and can also provide a choice for the prevention and treatment of liver metabolic diseases represented by NAFLD. PRACTICAL APPLICATION: Our study proved that MRJPs had substantial preventing effect on OA-induced lipid accumulation and mitochondrial dysfunction in HepG2 cells. This research can further provide theoretical support for the development and application of peptide drugs in the future. Besides, it can not only further broaden our understanding of NAFLD and other diseases, but also provide ideas for research on oxidative stress and lipid accumulation in the body.
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Affiliation(s)
- Xiaochen Zhang
- The State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, No. 130 Meilong Road, Xuhui District, Shanghai, 200237, China
| | - Xinyang Lu
- The State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, No. 130 Meilong Road, Xuhui District, Shanghai, 200237, China
| | - Yingjun Zhou
- The State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, No. 130 Meilong Road, Xuhui District, Shanghai, 200237, China
| | - Xinyu Guo
- The State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, No. 130 Meilong Road, Xuhui District, Shanghai, 200237, China
| | - Yaning Chang
- The State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, No. 130 Meilong Road, Xuhui District, Shanghai, 200237, China
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New insight and potential therapy for NAFLD: CYP2E1 and flavonoids. Biomed Pharmacother 2021; 137:111326. [PMID: 33556870 DOI: 10.1016/j.biopha.2021.111326] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 01/21/2021] [Accepted: 01/25/2021] [Indexed: 12/13/2022] Open
Abstract
Over the years, the prevalence of nonalcoholic fatty liver disease (NAFLD) has increased year by year; however, due to its complicated pathogenesis, there is no effective treatment so far. It is reported that Cytochrome P450 2E1 (CYP2E1) plays an indispensable role in the development of NAFLD, and numerous studies have shown that flavonoids have a hepatoprotective effect and can exert a beneficial effect on NAFLD by regulating the activity of CYP2E1. Therefore, flavonoids may become effective drugs for the treatment of NAFLD in the future. This prompted us to review the research progress of the pathological mechanism of NAFLD and the impact of CYP2E1 activity changes during the pathological process, and to summarize the protective effect of flavonoids against CYP2E1 activity.
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Zhang R, Yin L, Chen J, Zhang X. Antioxidant Capacity of Proteins and Hydrolysates from the Liver of Newborn Piglets, and Their Inhibitory Effects on Steatosis in vitro. Food Technol Biotechnol 2021; 58:455-464. [PMID: 33505208 PMCID: PMC7821780 DOI: 10.17113/ftb.58.04.20.6657] [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] [Indexed: 11/27/2022] Open
Abstract
Research background Non-alcoholic steatohepatitis is a potentially progressive hepatic disorder that can lead to end-stage liver disease and hepatocellular carcinoma. The inhibitory effects of proteins and hydrolysates from the liver of newborn piglets on hepatic steatosis in oleic acid-induced hepatocellular carcinoma (HepG2) cells were investigated in vitro. Experimental approach The extracted proteins from the liver of newborn piglets were hydrolysed with papain, pepsin, trypsin and Alcalase. Based on the comparison of different enzyme digestion conditions, a protein hydrolysis protocol was established to obtain hydrolysates with lipid-lowering effect. Results and conclusions Trypsin-digested liver protein hydrolysate from newborn piglets exhibited strong antioxidant activity and good inhibitory effects against lipogenesis and cholesterol accumulation in HepG2 cells at the concentration of 150 μg/mL, with a triglyceride decrease of (43±3) % and cholesterol decrease of (31±5) %, compared with model group induced with 0.75 mM oleic acid. The addition of trypsin-digested liver protein hydrolysate from newborn piglets (300 μg/mL) decreased alanine aminotransferase and aspartate aminotransferase activities and increased superoxide dismutase activity. Novelty and scientific contribution This study demonstrated that the trypsin-digested liver protein hydrolysate from newborn piglets has a potential preventive effect against non-alcoholic fatty liver disease in its early stage, and a potential use as the modulator of lipid overaccumulation in form of food supplements.
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Affiliation(s)
- Ruilin Zhang
- College of Food Science and Engineering, South China University of Technology, Wshan Road 381, 510640 Guangzhou, PR China
| | - Lasheng Yin
- College of Food Science and Engineering, South China University of Technology, Wshan Road 381, 510640 Guangzhou, PR China
| | - Jian Chen
- College of Food Science and Engineering, South China University of Technology, Wshan Road 381, 510640 Guangzhou, PR China
| | - Xuewu Zhang
- College of Food Science and Engineering, South China University of Technology, Wshan Road 381, 510640 Guangzhou, PR China
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Guo Z, Chen X, Huang Z, Chen D, Yu B, Chen H, Yu J, Yan H, Zheng P, Luo Y. Dietary dihydromyricetin supplementation enhances antioxidant capacity and improves lipid metabolism in finishing pigs. Food Funct 2021; 12:6925-6935. [PMID: 34132271 DOI: 10.1039/d0fo03094e] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Nowadays, chronic diseases have become a potential danger to human health and are highly concerning. Given that pigs are a suitable animal model for human nutrition and metabolism for its similar anatomical and physiological properties to those of humans, this study has used 24 castrated male Duroc × Landrace × Yorkshire (DLY) pigs as experimental subjects to explore the effects of dietary dihydromyricetin (DHM) supplementation on the antioxidant capacity and lipid metabolism. Results showed that dietary 300 and 500 mg DHM kg-1 diet supplementation increased the serum total superoxide dismutase (T-SOD) level, serum and liver reduced glutathione (GSH), muscle catalase (CAT) level and serum high-density lipoprotein cholesterol (HDL-C) level, and reduced the liver malondialdehyde (MDA) level and muscle triglyceride (TG) level in finishing pigs. Western blot analysis showed that dietary DHM supplementation activated the nuclear-related factor 2 (Nrf2) and AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signals. Real-time quantitative PCR analysis showed that dietary DHM supplementation upregulated the mRNA levels of lipolysis and fatty acid oxidation-related genes, and down-regulated the mRNA expression of lipogenesis-related genes in finishing pigs. Together, we provide evidence that dietary DHM supplementation improved the antioxidant capacity and lipid metabolism in finishing pigs.
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Affiliation(s)
- Zhongyang Guo
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China.
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Li W, Xiao H. Dihydromyricetin Alleviates High Glucose-Induced Oxidative Stress and Apoptosis in Human Retinal Pigment Epithelial Cells by Downregulating miR-34a Expression. Diabetes Metab Syndr Obes 2021; 14:387-397. [PMID: 33536772 PMCID: PMC7850407 DOI: 10.2147/dmso.s290633] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 12/12/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus, which leads to neuronal and vascular dysfunction in the retina with a final outcome of complete loss of vision. The aim of the present study was to investigate the effects of dihydromyricetin (DHM), a natural flavanol compound, on diabetic retinopathy (DR) and identify its potential mechanisms. METHODS Retinal pigment epithelial cell line (ARPE-19) treated with high glucose (HG) was used to simulate the DR model in vitro. After treatment with different concentrations of DHM, the cell viability, production of reactive oxygen species (ROS) and the levels of oxidative stress-related markers in the in vitro model were detected using corresponding kits. Cell apoptosis was determined using terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining, and the expression of apoptotic proteins was examined using Western blot analysis. Subsequently, microRNA (miR)-34a expression was measured by reverse transcription-quantitative PCR (RT-qPCR). The levels of oxidative stress and apoptosis were evaluated after miR-34a overexpression. RESULTS Results indicated that DHM dose-dependently elevated the decreased cell viability induced by HG. Moreover, the content of ROS was significantly reduced in HG-stimulated ARPE-19 cells, accompanied by enhanced activities of superoxide dismutase (SOD) and catalase (CAT) antioxidases, as well as concentration of glutathione (GSH). Furthermore, remarkably decreased apoptosis of ARPE-19 cells induced by HG was observed following DHM intervention. Importantly, HG stimulation notably upregulated miR-34a expression, which was reversed by DHM treatment. Importantly, the inhibitory effects of DHM on HG-induced oxidative stress and apoptosis of ARPE-19 cells were restored following miR-34a overexpression. CONCLUSION Taken together, this work demonstrated that DHM exerts protective effects on HG-induced oxidative stress and apoptotic damage in ARPE-19 cells via inhibition of miR-34a expression, providing a promising therapeutic agent for the treatment of DR.
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Affiliation(s)
- Wenjun Li
- Department of Ophthalmology, NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin300134, People’s Republic of China
| | - Hongxia Xiao
- Department of Ophthalmology, Jingmen No. 2 People’s Hospital, Jingmen448000, People’s Republic of China
- Correspondence: Hongxia Xiao Jingmen No. 2 People’s Hospital, 39 Xiangshan Avenue, Jingmen, Hubei448000, People’s Republic of China Email
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Li J, Li X, Liu D, Zhang S, Tan N, Yokota H, Zhang P. Phosphorylation of eIF2α signaling pathway attenuates obesity-induced non-alcoholic fatty liver disease in an ER stress and autophagy-dependent manner. Cell Death Dis 2020; 11:1069. [PMID: 33318479 PMCID: PMC7736876 DOI: 10.1038/s41419-020-03264-5] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 11/15/2020] [Accepted: 11/16/2020] [Indexed: 12/12/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder and frequently exacerbates in postmenopausal women. In NAFLD, the endoplasmic reticulum (ER) plays an important role in lipid metabolism, in which salubrinal is a selective inhibitor of eIF2α de-phosphorylation in response to ER stress. To determine the potential mechanism of obesity-induced NAFLD, we employed salubrinal and evaluated the effect of ER stress and autophagy on lipid metabolism. Ninety-five female C57BL/6 mice were randomly divided into five groups: standard chow diet, high-fat (HF) diet, HF with salubrinal, HF with ovariectomy, and HF with ovariectomy and salubrinal. All mice except for SC were given HF diet. After the 8-week obesity induction, salubrinal was subcutaneously injected for the next 8 weeks. The expression of ER stress and autophagy markers was evaluated in vivo and in vitro. Compared to the normal mice, the serum lipid level and adipose tissue were increased in obese mice, while salubrinal attenuated obesity by blocking lipid disorder. Also, the histological severity of hepatic steatosis and fibrosis in the liver and lipidosis was suppressed in response to salubrinal. Furthermore, salubrinal inhibited ER stress by increasing the expression of p-eIF2α and ATF4 with a decrease in the level of CHOP. It promoted autophagy by increasing LC3II/I and inhibiting p62. Correlation analysis indicated that lipogenesis in the development of NAFLD was associated with ER stress. Collectively, we demonstrated that eIF2α played a key role in obesity-induced NAFLD, and salubrinal alleviated hepatic steatosis and lipid metabolism by altering ER stress and autophagy through eIF2α signaling.
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Affiliation(s)
- Jie Li
- Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
- Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, 300070, China
| | - Xinle Li
- Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
- Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, 300070, China
| | - Daquan Liu
- Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
- Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, 300070, China
| | - Shiqi Zhang
- Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
| | - Nian Tan
- Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
| | - Hiroki Yokota
- Department of Biomedical Engineering, Indiana University-Purdue University, Indianapolis, IN, 46202, USA
| | - Ping Zhang
- Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
- Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, 300070, China.
- Department of Biomedical Engineering, Indiana University-Purdue University, Indianapolis, IN, 46202, USA.
- Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University, Tianjin, 300052, China.
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Cheng QC, Fan J, Deng XW, Liu HC, Ding HR, Fang X, Wang JW, Chen CH, Zhang WG. Dihydromyricetin ameliorates chronic liver injury by reducing pyroptosis. World J Gastroenterol 2020; 26:6346-6360. [PMID: 33244197 PMCID: PMC7656208 DOI: 10.3748/wjg.v26.i41.6346] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/30/2020] [Accepted: 08/29/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic liver injury (CLI) is now a worldwide disease. However, there is no effective treatment. Pyroptosis plays an essential role in CLI. Dihydromyricetin (DHM) resists oxidation and protects the liver. We hypothesize that the beneficial effect of DHM on CLI is related to its effect on the expression of pyroptosis-related molecules. Therefore, we studied the influence of DHM on CLI and pyroptosis.
AIM To study the role of pyroptosis in the pathogenesis of CLI and the therapeutic mechanism of DHM.
METHODS Thirty-two mice were randomly divided into four groups: The control group was injected with olive oil, the carbon tetrachloride (CCl4) group was injected with CCl4, the vehicle group was injected with hydroxypropyl-β-cyclodextrin while injecting CCl4 and the DHM group was injected with DHM while injecting CCl4. After four weeks of treatment, liver tissues from the mice were stained with hematoxylin and eosin, and oil red O. Blood was collected from the angular vein for serological analysis. The severity of CLI was estimated. Some liver tissue was sampled for immunohistochemistry, Western blotting and quantitative reverse transcription PCR to observe the changes in pyroptosis-related molecules.
RESULTS Serum total cholesterol, low density lipoprotein, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the CCl4 group were higher than those in the control group, and serum total cholesterol, low density lipoprotein, AST and ALT in the DHM group were lower than those in the vehicle group. Hematoxylin and eosin and oil red O staining showed that there were more lipid droplets in the CCl4 group than in the control group, and there were fewer lipid droplets in the DHM group than in the vehicle group. Western blotting showed that the expression of the pyroptosis-related molecules caspase-1, NOD-, LRR- and pyrin domain-containing 3 (NLRP3) and gasdermin D (GSDMD)-N in the CCl4 group was higher than that in the control group, while expression of these proteins in the DHM group was lower than that in the vehicle group. Quantitative reverse transcription PCR results showed that the expression of the pyroptosis-related genes caspase-1, NLRP3, GSDMD and interleukin-1β (IL-1β) in the CCl4 group was higher than that in the control group, while there was no significant change in NLRP3 and caspase-1 expression in the DHM group compared with that in the vehicle group, and the expression of GSDMD and IL-1β was decreased.
CONCLUSION DHM improves CCl4-induced CLI and regulates the pyroptosis pathway in hepatocytes. DHM may be a potential therapeutic agent for CLI.
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Affiliation(s)
- Quan-Cheng Cheng
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Jing Fan
- Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 202155, China
| | - Xin-Wei Deng
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Huai-Cun Liu
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Hui-Ru Ding
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Xuan Fang
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Jian-Wei Wang
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Chun-Hua Chen
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Wei-Guang Zhang
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
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Silva J, Yu X, Moradian R, Folk C, Spatz MH, Kim P, Bhatti AA, Davies DL, Liang J. Dihydromyricetin Protects the Liver via Changes in Lipid Metabolism and Enhanced Ethanol Metabolism. Alcohol Clin Exp Res 2020; 44:1046-1060. [PMID: 32267550 PMCID: PMC7211127 DOI: 10.1111/acer.14326] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 03/03/2020] [Indexed: 12/13/2022]
Abstract
Background Excess alcohol (ethanol, EtOH) consumption is a significant cause of chronic liver disease, accounting for nearly half of the cirrhosis‐associated deaths in the United States. EtOH‐induced liver toxicity is linked to EtOH metabolism and its associated increase in proinflammatory cytokines, oxidative stress, and the subsequent activation of Kupffer cells. Dihydromyricetin (DHM), a bioflavonoid isolated from Hovenia dulcis, can reduce EtOH intoxication and potentially protect against chemical‐induced liver injuries. But there remains a paucity of information regarding the effects of DHM on EtOH metabolism and liver protection. As such, the current study tests the hypothesis that DHM supplementation enhances EtOH metabolism and reduces EtOH‐mediated lipid dysregulation, thus promoting hepatocellular health. Methods The hepatoprotective effect of DHM (5 and 10 mg/kg; intraperitoneal injection) was evaluated using male C57BL/6J mice and a forced drinking ad libitum EtOH feeding model and HepG2/VL‐17A hepatoblastoma cell models. EtOH‐mediated lipid accumulation and DHM effects against lipid deposits were determined via H&E stains, triglyceride measurements, and intracellular lipid dyes. Protein expression of phosphorylated/total proteins and serum and hepatic cytokines was determined via Western blot and protein array. Total NAD+/NADH Assay of liver homogenates was used to detect NAD + levels. Results DHM reduced liver steatosis, liver triglycerides, and liver injury markers in mice chronically fed EtOH. DHM treatment resulted in increased activation of AMPK and downstream targets, carnitine palmitoyltransferase (CPT)‐1a, and acetyl CoA carboxylase (ACC)‐1. DHM induced expression of EtOH‐metabolizing enzymes and reduced EtOH and acetaldehyde concentrations, effects that may be partly explained by changes in NAD+. Furthermore, DHM reduced the expression of proinflammatory cytokines and chemokines in sera and cell models. Conclusion In total, these findings support the utility of DHM as a dietary supplement to reduce EtOH‐induced liver injury via changes in lipid metabolism, enhancement of EtOH metabolism, and suppressing inflammation responses to promote liver health.
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Affiliation(s)
- Joshua Silva
- From the, Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California
| | - Xin Yu
- From the, Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California
| | - Renita Moradian
- From the, Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California
| | - Carson Folk
- From the, Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California
| | - Maximilian H Spatz
- From the, Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California
| | - Phoebe Kim
- From the, Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California
| | - Adil A Bhatti
- From the, Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California
| | - Daryl L Davies
- From the, Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California
| | - Jing Liang
- From the, Titus Family Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California
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Cai N, Chen J, Bi D, Gu L, Yao L, Li X, Li H, Xu H, Hu Z, Liu Q, Xu X. Specific Degradation of Endogenous Tau Protein and Inhibition of Tau Fibrillation by Tanshinone IIA through the Ubiquitin-Proteasome Pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:2054-2062. [PMID: 31995984 DOI: 10.1021/acs.jafc.9b07022] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Alzheimer's disease (AD) is a common neurodegenerative disease which is partly characterized by the aggregation of hyperphosphorylated Tau proteins forming neurofibrillary tangles that promote AD pathogenesis. In this study, we investigated the effects of tanshinone IIA (Tan IIA) isolated from Salvia miltiorrhiza on Tau degradation in the treatment of AD. The results showed that Tan IIA reduced the Tau expression and attenuated Tau phosphorylation in N2a cells, Tau-overexpressing cells, and 3×Tg-AD mouse primary neuron cells. Moreover, Tan IIA increased polyubiquitinated Tau accumulation and induced proteasomal degradation of the Tau protein. Additionally, Tan IIA became bound to the Tau protein and inhibited the formation of heparin-induced Tau fibrils. In summary, Tan IIA can increase polyubiquitinated Tau accumulation and induce the proteasomal degradation of the Tau protein and the binding of Tan IIA to the Tau protein, inhibiting the formation of Tau fibrils. Tan IIA may be further explored as a potential candidate for AD treatment.
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Affiliation(s)
- Nan Cai
- Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography , Shenzhen University , Shenzhen 518060 , PR China
- Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering , Shenzhen University , Shenzhen 518060 , PR China
| | - Jiajie Chen
- Department of Biochemistry and Molecular Biology, School of Medicine , Shenzhen University , Shenzhen 518055 , PR China
| | - Decheng Bi
- Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography , Shenzhen University , Shenzhen 518060 , PR China
| | - Liang Gu
- Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography , Shenzhen University , Shenzhen 518060 , PR China
| | - Lijun Yao
- Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography , Shenzhen University , Shenzhen 518060 , PR China
| | - Xiuting Li
- Beijing Advanced Innovation Center for Food Nutrition and Human Health , Beijing Technology and Business University , Beijing 100000 , PR China
| | - Hui Li
- Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography , Shenzhen University , Shenzhen 518060 , PR China
| | - Hong Xu
- Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography , Shenzhen University , Shenzhen 518060 , PR China
| | - Zhangli Hu
- Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography , Shenzhen University , Shenzhen 518060 , PR China
| | - Qiong Liu
- Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography , Shenzhen University , Shenzhen 518060 , PR China
| | - Xu Xu
- Shenzhen Key Laboratory of Marine Bioresource and Eco-environmental Science, Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography , Shenzhen University , Shenzhen 518060 , PR China
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Chen L, Lin X, Teng H. Emulsions loaded with dihydromyricetin enhance its transport through Caco-2 monolayer and improve anti-diabetic effect in insulin resistant HepG2 cell. J Funct Foods 2020. [DOI: 10.1016/j.jff.2019.103672] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
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Tong H, Zhang X, Tan L, Jin R, Huang S, Li X. Multitarget and promising role of dihydromyricetin in the treatment of metabolic diseases. Eur J Pharmacol 2019; 870:172888. [PMID: 31866404 DOI: 10.1016/j.ejphar.2019.172888] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 12/01/2019] [Accepted: 12/18/2019] [Indexed: 12/30/2022]
Abstract
Dihydromyricetin (DMY or DHM), also known as ampelopsin, is the main natural flavonol compound extracted from the plant Ampelopsis grossedentata (Hand. -Mazz) W.T. Wang. In recent years, accumulating studies have been conducted to explore the extensive biological functions of DMY, including antitumor, anti-inflammation, organ-protective, and metabolic regulation effects. DMY acts as a potential preventive or therapeutic agent in treating multiple diseases, such as diabetes mellitus, atherosclerosis, nonalcoholic fatty liver disease and osteoporosis. This review article summarizes the preventive and therapeutic potential of DMY in multiple metabolic diseases and the main signaling pathways in which DMY participates to offer a comprehensive understanding and guidance for future studies.
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Affiliation(s)
- Haihui Tong
- Department of Pediatrics, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jie Fang Avenue, Wuhan, Hubei Province, 430022, China.
| | - Xuejun Zhang
- Department of Orthopedics, The People's Hospital of China Three Gorges University, First People's Hospital of Yichang, No. 4 Hudi Street, Yichang, Hubei Province, 443000, China.
| | - Lingfang Tan
- Department of Pediatrics, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jie Fang Avenue, Wuhan, Hubei Province, 430022, China.
| | - Runming Jin
- Department of Pediatrics, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jie Fang Avenue, Wuhan, Hubei Province, 430022, China.
| | - Shilong Huang
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Avenue, Wuhan, Hubei Province, 430030, China.
| | - Xin Li
- Department of Pediatrics, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jie Fang Avenue, Wuhan, Hubei Province, 430022, China.
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Liu YT, Lai YH, Lin HH, Chen JH. Lotus Seedpod Extracts Reduced Lipid Accumulation and Lipotoxicity in Hepatocytes. Nutrients 2019; 11:E2895. [PMID: 31795130 PMCID: PMC6950491 DOI: 10.3390/nu11122895] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 11/21/2019] [Accepted: 11/26/2019] [Indexed: 12/18/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders, including hepatic lipid accumulation and lipotoxicity. Plant-derived polyphenols have attracted considerable attention in the prevention of NAFLD. Lotus seedpod, rich in polyphenols, is a traditional Chinese herbal medicine. Previous studies have showed that lotus seedpod possess radioprotective, antioxidant, anti-cancer, and anti-inflammatory activities. In this study, the in vitro hepatoprotective effect of lotus seedpod extract (LSE) and its main component epigallocatechin (EGC) was examined. Firstly, oleic acid (OA), an unsaturated fatty acid, was used to induce the phenotype of NAFLD in human hepatocytes, HepG2 cells. LSE dose-dependently improved the OA-induced viability loss of HepG2 cells. Non-cytotoxic concentrations of LSE or EGC abolished intracellular lipid accumulation and oxidative stress in the OA-treated cells. In addition, LSE and EGC showed a minor effect on autophagy, and potential in reducing OA-induced occurrence of apoptosis confirmed by morphological and biochemical features, including an increase in the formation of apoptotic bodies, the exposure of phosphatidylserine, and activation of caspases. Molecular data showed the anti-apoptotic effect of LSE might be mediated via downregulation of the mitochondrial pathway. Our data imply that EGC-enriched LSE potentially could be developed as an anti-NAFLD agent.
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Affiliation(s)
- Yen-Tze Liu
- Department of Family Medicine, Changhua Christian Hospital, No. 135 Nanhsiao Street, Changhua City 50006, Taiwan;
| | - Yen-Hsun Lai
- Department of Nutrition, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung City 40201, Taiwan;
| | - Hui-Hsuan Lin
- Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung City 40201, Taiwan
- Department of Clinical Laboratory, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung City 40201, Taiwan
| | - Jing-Hsien Chen
- Department of Nutrition, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung City 40201, Taiwan;
- Department of Clinical Laboratory, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung City 40201, Taiwan
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Zhang J, Zhang SD, Wang P, Guo N, Wang W, Yao LP, Yang Q, Efferth T, Jiao J, Fu YJ. Pinolenic acid ameliorates oleic acid-induced lipogenesis and oxidative stress via AMPK/SIRT1 signaling pathway in HepG2 cells. Eur J Pharmacol 2019; 861:172618. [DOI: 10.1016/j.ejphar.2019.172618] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 08/15/2019] [Accepted: 08/16/2019] [Indexed: 12/20/2022]
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