The traditional Chinese medicine formula, Chaihu-Shugan-San, provides effective treatment for liver fibrosis through modulating inflammation responses, inhibiting angiogenesis, and regulating ECM remodeling.
To uncover the therapeutic workings of Chaihu-Shugan-San (CHSGS) against liver fibrosis, the researchers employed a network pharmacology approach along with single cell and bulk transcriptomics. Initially, they identified 134 bioactive ingredients in CHSGS meeting certain criteria. Using these, they predicted 1150 genes to be impacted by CHSGS. Simultaneously, 625 liver fibrosis-related genes were picked out via single cell transcriptomics analysis. From these, they recognized 71 intersecting genes between CHSGS and liver fibrosis leading to the identification of 21 core targets and 12 core ingredients of CHSGS against liver fibrosis.
The findings reveal that the key mechanisms for the formula's antifibrotic action involve the adjustment of inflammatory reactions, hindrance of angiogenesis, and the control of Extracellular Matrix (ECM) remodeling, with ECM remodeling regulation being of paramount importance. Validation of these mechanisms was carried out with molecular docking simulation which corroborated the strong interaction between the core targets and ingredients. Moreover, a 62-gene signature correlated with prognosis in cirrhotic patients was identified, potentially helping improve their survival chances through interaction with CHSGS.
