Yin-chen Wu-ling powder alleviate cholestatic liver disease: Network pharmacological analysis and experimental validation

• Published in: Gene 2023-01, Vol.851, p.146973-146973, Article 146973
• Main Authors: You, Li-Ping, Wang, Kai-Xia, Lin, Jia-Cheng, Ren, Xiao-Yu, Wei, Yu, Li, Wen-Xuan, Gao, Yue-Qiu, Kong, Xiao-Ni, Sun, Xue-Hua
• Format: Article
• Language: English
• Subjects: AKT; cholestasis; Cholestatic liver disease; genes; inflammation; interleukin-10; interleukin-6; isorhamnetin; liver diseases; p38MAPK; pharmacology; quercetin; sitosterols; therapeutics; Traditional Chinese medicine; ursodeoxycholic acid; Yin-chen Wu-ling Powder
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2022.146973

•This study firstly revealed the multiple active ingredients, potential targets, and possible mechanism of YWP to treat CLD based on network pharmacology Analysis and molecular docking.•We firstly demonstrated that YWP can reduce cholestasis in Mdr2-/- mice and the mechanism is related to the improved inflammatory response via inhibiting AKT and P38MAPK signaling.•The study found that hederagenin and cerevisterol from of YWP may be potential FXR activity inhibitors through molecular docking. Yin-chen Wu-ling Powder (YWP) has potential therapeutic effects on cholestatic liver disease (CLD), however, its active compounds and conceivable mechanism are as yet indistinct. Methods: The network pharmacology and gene function annotation examined the multiple active ingredients, potential targets, and possible mechanisms of YWP in CLD treatment. Then the molecular docking reassured the reliability of the core compounds including the key genes and farnesoid X receptor (FXR). Finally, The Mdr2-/- mice were used to test the effect and mechanism of YWP against CLD. Results: The network analysis identified nine main active ingredients, including quercetin, capillarisin, eupalitin, isorhamnetin, skrofulein, genkwanin, cerevisterol, gederagenin, and sitosterol. The PPI network predicted the ten hub genes involved were AKT1, MAPK1, MAPK14, IL6, RXRA, ESR1, IL10, NCOA1, CAV1, and EGFR. The KEGG and GO analysis showed that YWP might contribute to CLD treatment through the PI3K/Akt and MAKP signalings to manage pathological reactions, for instance, inflammatory responses. The molecular docking displayed a functional similarity among the core compounds with ursodeoxycholic acid (UDCA) and Obeticholic acid (OCA) on the effects on AKT1, MAPK1, MAPK14, RXRA, and ESR, and the affinity to FXR. In addition, the YWP could significantly attenuate hepatic injury and improve inflammatory response in Mdr2-/- mice. The mechanism exploration showed that YWP mainly decreased inflammatory response by inhibiting AKT/P38MAPK signaling. Conclusion: This study firstly revealed the multiple active ingredients, potential targets, and possible mechanism of YWP to treat CLD based on network pharmacology Analysis and molecular docking. YWP could alleviate cholestasis in Mdr2-/- mice by impairing inflammation via inhibiting AKT/P38MAPK Signaling.