Investigation of the potential mechanism of the Shugan Xiaozhi decoction for the treatment of nonalcoholic fatty liver disease based on network pharmacology and molecular docking

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is a metabolic-related disease with its incidence increasing annually. Shugan Xiaozhi (SGXZ) decoction, a composite traditional Chinese medicinal prescription, was demonstrated to exert a therapeutic effect on NAFLD. However, the underlying mechanisms were incompletely elucidated. In this study, the potential bioactive ingredients and mechanism of the SGXZ decoction against NAFLD were explored via network pharmacology and molecular docking. Methods: Compounds in SGXZ decoction were identified and collected from literature studies, and the corresponding targets were predicted through SEA database. Potential targets related to NAFLD were overlapped by using DisGeNET and GeneCards database. The compound-target-disease and PPI network were then constructed based on the putative intersection targets of SGXZ decoction and NAFLD to recognize the key compounds and targets. Functional enrichment analysis was performed to elucidate the biological process and signaling pathway that SGXZ decoction treated NAFLD. Finally, molecular docking combined with homology modeling was applied to further verify the binding between key active compounds and targets.Results: A total of 31 active compounds and 220 corresponding targets in SGXZ decoction were collected. Moreover, 1544 overlapped targets of NAFLD were obtained, of which 78 common targets were intersected with targets of SGXZ decoction. Key compounds and targets were recognized from compound-target-disease and PPI network. Functional enrichment analysis revealed that multiple biological pathways were annotated including insulin resistance, HIF-1, PI3K-Akt, and MAPK signaling pathways. Molecular docking confirmed that gallic acid, chlorogenic acid and isochlorogenic acid A could combine firmly with all of the key targets. Conclusion: SGXZ decoction could produce a promising effect for its multi-component, multi-target and multi-biological process in the treatment of NAFLD. The present study provides the novel insight into a comprehensive understanding for further study.

VSpipe-GUI, an Interactive Graphical User Interface for Virtual Screening and Hit Selection

“…Recently, Onyango et al [17] used VSpipe-CLI for in silico identification of new anti-SARS-CoV-2 main protease (M pro ) molecules. Similarly, various studies have used VSpipe-CLI in identifying hit compounds against selected drug targets such as protein tyrosine phosphatases or a fungal methionine synthase [18][19][20][21].…”