Exploring the protective effect of Modified Xiaochaihu Decoction against hepatic steatosis and inflammation by network p
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Chinese Medicine Open Access
RESEARCH
Exploring the protective effect of Modified Xiaochaihu Decoction against hepatic steatosis and inflammation by network pharmacology and validation in ageing rats Siting Gao1,2, Tongzhuang Wang1,2, XueKuan Huang1,2, Yaqian Jin1,3, Yu Xu1,2, Yumeng Xi1,2, Jun Zhang1,3, Yan Luo1,2, Hongling Xu1,2, Hongli Guo1,2, Dazhi Ke4 and Jianwei Wang1,2*
Abstract Background: Based on therapy with syndrome differentiation and clinical studies on Xiaochaihu decoction (XCHD), we hypothesize that Modified Xiaochaihu Decoction (MXD) has an ability to ameliorate non-alcoholic fatty liver disease (NAFLD). This study aims to elucidate the pharmacological efficacy of MXD and its mechanism in the treatment of NAFLD by network pharmacology and experimental validation. Methods: The active ingredients in MXD and their potential targets were identified using network analysis followed by experimental validation. First, we used data on the ingredients and targets obtained from professional database and related literature to do PPI network analysis, GO functional analysis, and KEGG pathway enrichment analysis. Core targets identified by network pharmacology were then tested in natural ageing female rats model. Indexes of lipid and glucose homeostasis were determined enzymatically and/or histologically. Gene expression was analyzed by realtime PCR and/or Western blot (WB). Results: In total, 4009 NAFLD-related targets and 1953 chemical ingredients of MXD were obtained. In-depth network analysis of 140 common targets indicated that MXD played a critical role in anti-NAFLD via multiple targets and pathways. Based on the data of PPI analysis, GO functional enrichment analysis, KEGG pathway enrichment analysis, and literatures on the mechanism of NAFLD, we chose the core targets related to lipid metabolism (SREBP-1c, ChREBP, FASN, PPARα, and ACACA) and inflammation (IL-6 and NF-κB) to do further study. Significantly, in further animal verification experiment we using naturally ageing rats with NAFLD as a model, we found that MXD administration ameliorated age-related NAFLD and mechanistically down-regulated the mRNA/protein expression of core targets in lipid metabolism and inflammation related pathways such as FASN, ACACA, IL-6, and NF-κB. In addition, 12 of 24 potential ingredients acting on verified targets came from BC, and 11 of 24 potential ingredients acting on verified targets were derived from SM, implying that both BC and SM served as the key role in MXD against NAFLD.
*Correspondence: [email protected]; [email protected] 1 Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing, China Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the orig
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