Exploration of the Molecular Basis of Forsythia Fruit in the Prevention and Treatment of Cholestatic Liver Injury through Network Pharmacology and Molecular Docking

• Published in: Nutrients Vol. 15; no. 9; p. 2065
• Main Authors: Fu, Ke, Li, Yanzhi, Dai, Shu, Li, Yunxia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.04.2023; MDPI
• Subjects: Animals; Apoptosis; Bile ducts; Cancer; Cholangitis; Cholestasis; Cholestasis - drug therapy; Collagen; Disease prevention; Drugs; Extracellular matrix; Fibrosis; Forsythia; forsythia fruit; forsythoside A; Fruit; Fruits; Functional foods; Functional foods & nutraceuticals; Gallbladder diseases; Gelatinase A; Herbal medicine; Inflammation; Injury prevention; Ligands; Liver; Liver diseases; Metabolites; Mice; Molecular docking; Molecular Docking Simulation; MyD88 protein; Network Pharmacology; NF-kappa B; NF-κB protein; Pharmacology; Pruritus; Software; Synaptotagmin; TLR4 protein; TLR4/NF-κB pathway; Toll-Like Receptor 4 - genetics; Toll-like receptors; forsythia fruit; molecular docking; forsythoside A; TLR4/NF-κB pathway; cholestasis; network pharmacology
• DOI: 10.3390/nu15092065
• ISSN: 2072-6643

Forsythia fruit, edible fruit of (Thunb.) Vahl, which has been found to be effective in treating cholestasis. However, its key component for alleviating cholestasis has not been determined. In this study, four representative active ingredients in forsythia fruit were selected. Through network pharmacology and molecular docking technology, we tried to find the key component for its treatment of cholestasis. Furthermore, the model of cholestasis in mice was established to verify the protective effect of the key component on cholestasis. Network pharmacology and molecular docking showed that forsythoside A (FTA) is the key component of forsythia fruit in the treatment of cholestasis. In vivo experiments revealed that FTA treatment could alleviate liver injury, dysfunction, and collagen deposition induced by cholestasis in mice. At the same time, FTA treatment inhibited inflammatory factor release and fibrosis-related factor expression. In addition, FTA treatment also reduced MMP-2, TLR4, MYD88, NF-κB p65, and -NF-κB p65 protein expression. In conclusion, FTA, a key component of forsythia fruit, alleviated liver damage and fibrosis caused by cholestasis via inhibiting the TLR4/NF-κB pathway, extracellular matrix accumulation, and inflammatory cytokine expression. The research results could provide a scientific reference for the development of forsythia fruit as a drug or functional food to prevent and treat cholestasis.