Abstract
Chinese medicine formulae possess the potential for cholestasis treatment. This study aimed to explore the underlying mechanisms of San-Huang-Chai-Zhu formula (SHCZF) against cholestasis. The major chemical compounds of SHCZF were identified by high-performance liquid chromatography. The bioactive compounds and targets of SHCZF, and cholestasis-related targets were obtained from public databases. Intersected targets of SHCZF and cholestasis were visualized by Venn diagram. The protein-protein interaction and compound-target networks were established by Cytoscape according to the STRING database. The biological functions and pathways of potential targets were characterized by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The biological process-target-pathway network was constructed by Cytoscape. Finally, the interactions between biological compounds and hub target proteins were validated via molecular docking. There 7 major chemical compounds in SHCZF. A total of 141 bioactive compounds and 83 potential targets were screened for SHCZF against cholestasis. The process of SHCZF against cholestasis was mainly involved in AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and drug metabolism-cytochrome P450. ALB, IL6, AKT1, TP53, TNF, MAPK3, APOE, IL1B, PPARG, and PPARA were the top 10 hub targets. Molecular docking showed that bioactive compounds of SHCZF had a good binding affinity with hub targets. This study predicted that the mechanisms of SHCZF against cholestasis mainly involved in AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and drug metabolism-cytochrome P450. Moreover, APOE, AKT1, and TP53 were the critical hub targets for bioactive compounds of SHCZF.
Highlights
Cholestasis is a common clinical manifestation of liver disease mainly derived from the reduction or obstruction of bile flow [1]
A total of 141 bioactive compounds and 83 potential targets were screened for San-Huang-Chai-Zhu formula (SHCZF) against cholestasis
Molecular docking showed that bioactive compounds of SHCZF had a good binding affinity with hub targets
Summary
Cholestasis is a common clinical manifestation of liver disease mainly derived from the reduction or obstruction of bile flow [1]. Accumulating evidence indicated that Chinese medicines exert beneficial therapeutic effects in liver diseases and cholestasis [5, 6]. San-Huang-Chai-Zhu formula (SHCZF) is a Chinese herbal formula, which consists of five herbs, namely, Dahuang (Rhei Radix Et Rhizome), Huangbai (Phellodendri Chinrnsis Cortex), Huangzhizi (Gardeniae Fructus), Chaihu (Radix Bupleuri), and Baizhu (Atractylodes Macrocephala Koidz.). Previous studies indicated that these five herbs all possess the hepatoprotective effect on liver diseases. Cao et al [7] reported that Dahuang had extensive pharmacological effects in hepatoprotective, anti-inflammatory, anticancer and so on. Saikosaponins extracted from Chaihu showed valuable pharmacological activities of anti-inflammatory and liver protection [10]. Baizhu in Xiaoyao San formula was validated its pharmacological effects of hepatoprotection [11]. The underlying pharmacological mechanism of SHCZF against cholestasis is still illusive
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