Combination of omics, bioinformatics, molecular docking, and experimental validation to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen

Abstract

AbstractOmics, bioinformatics, molecular docking, and experimental validation were used to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen (SDG) based on the biolabel‐led research pattern. Integrated omics were used to explore the biolabels of SDG intervention in liver tissue. Subsequently, bioinformatics and molecular docking were applied to topologically analyze its therapeutic effects, mechanisms, and active compounds based on biolabels. Finally, an animal model was used to verify the biolabel analysis results. Omics, bioinformatics, and molecular docking revealed that SDG may exert therapeutic effects on liver diseases in the multicompound and multitarget synergistic modes, especially liver cirrhosis. In the validation experiment, SDG and its active compounds (betulinic acid and gallic acid) significantly improved the liver histopathological damage in the CCl4‐induced liver cirrhosis model. Meanwhile, they also produced significant inhibitory effects on the focal adhesion pathway (integrin alpha‐1, myosin regulatory light chain 2, laminin subunit gamma‐1, etc.) and alleviated the associated pathological processes: focal adhesion (focal adhesion kinase 1)–extracellular matrix (collagen alpha‐1(IV) chain, collagen alpha‐1(VI) chain, and collagen alpha‐2(VI) chain) dysfunction, carcinogenesis (alpha‐fetoprotein, NH3, and acetylcholinesterase), inflammation (tumor necrosis factor alpha, interleukin‐1 [IL‐1], IL‐6, and IL‐10), and oxidative stress (reactive oxygen species, malonaldehyde, and superoxide dismutase). This study provides new evidence and insights for the hepatoprotective effects, mechanisms, and active compounds of SDG.