Network pharmacology analysis on mechanism of Jian Pi Qing Gan Yin decoction ameliorating high fat diet-induced non-alcoholic fatty liver disease and validated in vivo. (15th September 2022)

• Record Type: Journal Article
• Authors: Liu, Weiwei; Shang, Jingyu; Deng, Yinxiang; Han, Xiuzhen; Chen, Yugen; Wang, Shuangshuang; Yang, Ruwen; Dong, Fan; Shang, Hongtao
• Is Part Of: Journal of ethnopharmacology. Volume 295(2022)
• Publication Date: 2022-09-15
• Subjects: Non-alcoholic fatty liver disease -- Chinese medicine -- Jian Pi Qing Gan Yin -- Network pharmacology; JPQGY Jian Pi Qing Gan Yin -- NAFLD Non-alcoholic fatty liver disease -- BMI Body mass index -- H&E Hematoxylin and eosin -- NAFL Non-alcoholic fatty liver -- NASH Non-alcoholic steatohepatitis -- TCM Traditional Chinese medicine -- LDL Low-density lipoprotein -- HDL High-density lipoprotein -- HFD High-fat diet -- TC Cholesterol -- TG Triglyceride -- AST Aspartate aminotransferase -- ALT Alanine aminotransferas -- FFA Free fatty acid -- CGA Chlorogenic acid -- NAS NAFLD activity scores -- CHM Chinese herbal medicine -- NFκB Nuclear factor kappa B -- SREBP Sterol regulatory element-binding protein -- LXRs Liver X receptors -- AMPK AMP-activated protein kinase -- PPAR Peroxisome proliferator-activated receptor -- CYP2E1 Cytochrome P450 2E1; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.115382
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Jian Pi Qing Gan Yin (JPQGY) has been used clinically to relieve non-alcoholic fatty liver disease (NAFLD) in China for decades; however, the underlying mechanisms of JPQGY remain unclear. Aim of the study: We evaluated the effects and mechanisms of JPQGY and hepatic steatosis caused by the middle stage of 13-week-high-fat-diet-induced NAFLD in mice. Materials and methods: Different dosages of JPQGY (5.5, 11, and 22 g/kg/day) were administered to NAFLD mice simultaneously. Body weight, body mass index (BMI), and liver lipid- and inflammation-related serum indicators were measured enzymatically. Liver samples were stained with Oil Red O and hematoxylin and eosin (H&E). Next, we performed a network pharmacology analysis and verified eight target genes mapping to NAFLD-related lipid metabolism pathways. The mRNA/protein expression was analyzed by real-time polymerase chain reaction (PCR) and western blotting. Results: JPQGY significantly relieved histological damage (steatosis-inflammation-fibrosis), prevented the downregulation of AMPK and Pparα, and upregulated LXRα, Srebp-1c, F4/80, Nf-κb, and Cyp2e1 in the HFD-induced NAFLD mouse model. Conclusions: The present results suggest that chronic treatment with JPQGY ameliorated HFD-induced NAFLD in mice by targeting the first and second phases of hepatic steatosis by stimulating the AMPK/PPARα pathway and inhibiting the LXRα/Srebp1/Nf-κb pathway. Our findings provide evidence that supports the clinical use of this formula for high-fat diet-induced fatty liver disease. Graphical abstract: Image 1 Highlights: Jian Pi Qing Gan Yin (JPQGY) ameliorated high-fat diet-induced NAFLD in mice. Network pharmacology analysis revealed JPQGY regulating 10 NAFLD-associated lipid metabolism pathways. JPQGY regulated the AMPK/PPARα pathway. JPQGY inhibited the LXRα/Srebp1/Nf-κb pathway in the livers of NAFLD mice.