Network pharmacology analysis and molecular docking to unveil the potential mechanisms of San-Huang-Chai-Zhu formula treating cholestasis

Abstract

Objective 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. Methods 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. Results 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. Conclusions 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.

Mechanism analysis of Buyang Huanwu decoction in treating atherosclerosis based on network pharmacology and in vitro experiments

“…These genes are mainly enriched in “lipid and atherosclerosis” and “AGE‐RAGE signaling pathway”, implying that BYHWT plays a key role in modulating lipid metabolism and inflammatory response. AGE‐RAGE pathway is an important modulator of inflammatory response involved in the pathogenesis of multiple diseases, including cardiovascular diseases (Liu et al., 2022). In this study, a total of 31 genes were enriched in this pathway, including four of the eight core targets, AKT1, MAPK1, JUN and PIK3CA, indicating that BYHWT exerts anti‐AS function by regulating the AGE‐RAGE signaling.…”

The IDI1/SREBP2 axis drives intrahepatic cholestasis and is a treatment target of San-Huang-Cai-Zhu formula identified by sequencing and experiments

“…In a previous study, we have clarified the mechanism by which SHCZF improves cholestasis through mitochondrial oxidative stress ( Liu et al, 2022b ). We also screened essential bioactive ingredients and possible target genes of SHCZF through network pharmacology ( Liu et al, 2022a ). However, no study has directly confirmed the effect of SHCZF on cholesterol metabolism-related pathways.…”

“…We have confirmed that SHCZF can ameliorate IHC in rats by regulating the expression of CYP4A1, HACL1, and F11R ( Yao et al, 2021 ) and dose-dependently improve IHC-induced liver injury by inhibiting SIRT1/PGC-1α and mitochondrial oxidative stress ( Liu et al, 2022b ). Through network pharmacology and molecular docking, we also identified possible bioactive components in SHCZF, such as chrysin and rhodopsin, that can target AKT1 and TP53 for the treatment of AIC in rats ( Liu et al, 2022a ). To provide more convincing data supporting the clinical promotion of SHCZF, we screened and validated the mechanisms of SHCZF in treating AIC from a more comprehensive perspective through sequencing and bioinformatics analysis.…”

Application of Bioinformatics Technology to Analyse the Mechanism of Guizhi Fuling Capsule in Treating Chronic Pelvic Inflammation

“…The AGE-RAGE regulates the release of inflammatory factors mainly by inducing oxidative stress and acting on downstream Jun N-terminal Kinase (JNK), Extracellular signal-Regulated protein Kinases 1 and 2 (ERK1/2), and Serine/Threonine Kinase (Akt). Studies have shown that overexpression of Nonsteroidal Antiinflammatory drug-activated Gene-1/Growth Differentiation Factor 15 (NAG-1/GDF15) can inhibit renal and systemic inflammation in mice, the AGE/RAGE axis, its downstream inflammatory molecules and adhesion molecules [23] . Another study showed that the AGE-RAGE signaling pathway in diabetic complications is one of the main signaling pathways involved in the anticholestasis process of the San-Huang-Chai-Zhu Formula (SHCZF) [24] .…”