Dataset Information

Protective effects and mechanisms of Lizhong decoction against non-alcoholic fatty liver disease in a rat model.

ABSTRACT:

Objective

To investigate the protective effects and molecular mechanisms of Lizhong decoction (, LZD) against non-alcoholic fatty liver disease (NAFLD).

Methods

Male Wistar rats were fed a high-fat diet for four weeks to induce NAFLD, and were administered LZD by gavage for four weeks. Potential therapeutic targets for NAFLD were analyzed using network pharmacology. Liver pathology was evaluated using Oil Red O and hematoxylin-eosin staining. Furthermore, mitochondrial function, lipid metabolism, oxidative stress, and inflammatory response were examined.

Results

Rats with NAFLD exhibited high levels of hepatic damage and cholesterol deposition. Moreover, apoptosis was increased, superoxide dismutase and glutathione content were reduced, malondialdehyde content was increased, and the protein expression of inflammatory cytokines and p-c-Jun N-terminal kinase was increased. The LZD treatment ameliorated mitochondrial dysfunction, reduced liver damage, inhibited oxidative stress and inflammatory response, upregulated peroxisome proliferator-activated receptor (PPAR)-γ expression, and suppressed dipeptidyl peptidase 4 (DPP4) expression in the liver.

Conclusion

It was found that LZD alleviates NAFLD by activating PPAR-γ and inhibiting DPP4.

SUBMITTER: Jiayao Y

PROVIDER: S-EPMC9924662 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Protective effects and mechanisms of Lizhong decoction against non-alcoholic fatty liver disease in a rat model.

Jiayao Yang Y Dongqing Tao T Wei M A MA Song Liu L Yan Liao L Lei Shu S Shu Zhang Z Chenyu L I LI Nianlong D U DU

Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan 20221001 5

<h4>Objective</h4>To investigate the protective effects and molecular mechanisms of Lizhong decoction (, LZD) against non-alcoholic fatty liver disease (NAFLD).<h4>Methods</h4>Male Wistar rats were fed a high-fat diet for four weeks to induce NAFLD, and were administered LZD by gavage for four weeks. Potential therapeutic targets for NAFLD were analyzed using network pharmacology. Liver pathology was evaluated using Oil Red O and hematoxylin-eosin staining. Furthermore, mitochondrial function, l ...[more]

PMID: 36083485

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Project description:BackgroundNon-alcoholic fatty liver (NAFLD) is a chronic disease worldwide, which poses a huge threat to human health. Xiaochaihu decoction is a well-known traditional Chinese medicine prescription. It has been proven effective in treating NAFLD but its mechanism is still unclear.ObjectiveMultiple mechanisms of Xiaochaihu decoction are explored by identifying and connecting potential targets and active ingredients in the treatment of NAFLD.MethodsActive ingredients and related targets of seven herbs were collected from TCMSP database. The related targets of NAFLD were obtained from Genes cards database, TDD and OMIM database. The intersected targets of disease targets and drug targets were input into STRING database to construct protein-protein interaction network. DAVID database was used for GO enrichment analysis and KEGG enrichment analysis.ResultsAfter screening and removal of duplicates, a total of 145 active ingredients and 105 potential targets were obtained. PPI network manifested that AKT1, IL6, JUN MAPK8 and STAT3 were the key target proteins. The results of GO enrichment analysis mainly involved cytokine receptor binding, cytokine activity, and heme binding. The results of KEGG analysis suggested that the mechanism mainly involved in AGE-RAGE signaling pathway in diabetic complications, Hepatitis C, fluid shear stress and atherosclerosis. The signaling pathways were further integrated as network manner, including AGE-RAGE signaling pathway in diabetic complications, Fluid shear stress and atherosclerosis, Insulin resistance, HIF-1 signaling pathway, Th17 cell differentiation and IL-17 signaling pathway. The network contained immunity regulation, metabolism regulation and oxidative stress regulation.ConclusionXiaochaihu decoction plays a key role in the treatment of NAFLD with multiple targets and pathways. Immunity regulation, metabolism regulation and oxidative stress regulation consist of the crucial regulation cores in mechanism.Graphical abstractDesign and workflow of this study.

Project description:Liver fibrosis is the excessive expression and accumulation of extracellular matrix proteins in the liver. Fibrotic scarring occurs as the consequence of chronic injury and inflammation. While the successful treatment of hepatitis B and C reduced the burden of liver disease related to viral hepatitis, non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) are nowadays the leading causes of hepatic fibrosis worldwide. Although basic research activities have significantly advanced our understanding of the molecular disease pathogenesis, the present therapeutic options for fibrosis are still limited. In advanced disease stages, liver transplantation often remains the only curative treatment. This highlights the necessity of preventive strategies to avoid complications of fibrosis, particularly cirrhosis, portal hypertension and liver cancer. Lifestyle modifications (weight loss, exercise, healthy diet) are the basis for prevention and treatment of NAFLD-associated fibrosis. In the present review, we discuss recent advances in antifibrotic prevention and therapy. In particular, we review the current concepts for antifibrotic drug candidates in the treatment of NAFLD and NASH. While some compounds aim at reverting pathogenic liver metabolism, an alternative approach is to disconnect the injury (e.g., NAFLD) from inflammation and/or fibrosis. Investigational drugs typically target metabolic pathways, insulin resistance, hepatocyte death, inflammatory cell recruitment or activation, the gut-liver axis, matrix expression or matrix turnover. While several promising drug candidates failed in phase 2 or 3 clinical trials (including elafibranor, emricasan and selonsertib), promising results with the farnesoid X receptor agonist obeticholic acid, the pan-PPAR agonist lanifibranor and the chemokine receptor CCR2/CCR5 inhibitor cenicriviroc support the expectation of an effective pharmacological therapy for liver fibrosis in the near future. Tackling NAFLD-associated fibrosis from different directions by combinatorial drug treatment and effective lifestyle changes hold the greatest prospects.

Dataset Information

Protective effects and mechanisms of Lizhong decoction against non-alcoholic fatty liver disease in a rat model.

Objective

Methods

Results

Conclusion

Publications

Protective effects and mechanisms of Lizhong decoction against non-alcoholic fatty liver disease in a rat model.

Similar Datasets

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