AUTHOR=Wu Jiashuo , Zhang Fangqing , Ruan Haonan , Chang Xiaoyan , Wang Jingxun , Li Zhuangzhuang , Jin Weiyi , Shi Yue 

TITLE=Integrating Network Pharmacology and RT-qPCR Analysis to Investigate the Mechanisms Underlying ZeXie Decoction-Mediated Treatment of Non-alcoholic Fatty Liver Disease

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.722016

DOI=10.3389/fphar.2021.722016

ISSN=1663-9812

ABSTRACT=ZeXie Decocation (ZXD) is a traditional Chinese medicine composed of Alisma orientalis (Sam.) Juzep. and Atractylodes macrocephala Koidz. that has been widely used to treat non-alcoholic fatty liver disease (NAFLD). The mechanistic basis for the pharmacological activity of ZXD, however, remains poorly understood. In this study, a network pharmacology approach was employed to understand the association between ZXD and NAFLD. The active ingredients in ZXD were identified and potential targets of these ingredients were screened, after which a database of relevant NAFLD related targets were constructed and several enrichment analyses were performed. Furthermore, the ethanol and aqueous extracts of ZXD were prepared and experimental pharmacology validation was conducted by RT-qPCR analyses of the oleic acid-induced lipid accumulation model in human hepatoma cells (HepG2). As a result, an herb-compound-target-pathway network model was created and the targets HMGCR, SREBP-2, MAPK and NF-κB of which were validated. The gene expression results of the 4 targets were consistent with the prediction of network pharmacology. Our study reveals through an integration strategy that ZXD can treat NAFLD by targeting HMGCR, SREBP-2, MAPK and NF-κB.