Exploring the Effect of Corydalis Yanhusuo on Hepatoc ellular Carcinoma Mechanism through Network Pharma cology,Molecular docking and In Vitro Experiments

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Abstract

Object: The study was conducted using network pharmacology (NP) and experimental validation as a base to identify potential targets and mechanisms of action of Corydalis yanhusuo (YHS) in treating Hepatocellular Carcinoma (HCC). Methods: : Traditional Chinese Medicine Systems Pharmacology (TCMSP) databasewas utilized to select effective YHS components, while the SymMap database was used to predict target proteins associated with effective components, and genes that could be related to HCC were selected using the GeneCards database. The Venn platform was used to obtain targets shared by YHS and HCC. Later, a String webserver was used to build protein-protein interaction (PPI) network, while a drug-component-target network was created using Cytoscape. GO and KEGG analysis was performed to parse biological processes and linked pathways connected to YHS in the treatment of HCC. Molecular docking technology was used to analyze the optimal effective components. The in vitro experiment on the HepG2 cell model confirmed the NP results. Results: : In total, 48 effective components and 88 shared targets were obtained. The main active ingredients identified were quercetin, hyndarin, isocordinine, (S)-Scoulerine, leonticine, and (R)-Canadine. The target-pathway network had 11 proteins and 211 pathways. Hub genes, in the PPI network included TP53, TNF, AKT1, MAPK1, IGF2, CDKN2A, TGFB1, MYC, CASP8, IL6, and CASP3. Moreover, as revealed by GO and KEGG analysis, Hepatitis B, the MAPK pathway, and the TNF pathway were all strongly linked to YHS's impact on HCC. Moreover, as demonstrated by in vitro experiments, YHS displayed remarkable activity in the treatment of HCC, most likely by regulating cell growth and apoptosis via MAPK pathways. Conclusion: The present work suggests that NP-based analyses combined with experimental validation provide an efficient approach for characterizing the mechanism of YHS in the treatment of HCC.

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License: CC-BY-4.0