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Shuimeng Zhan,1,* Xinyan Lu,1,* Hongyan Guo,1 Yang Liu,1 Zhi Li,1 Wei Xu,2 Fang Xia,2 Huanjun Tang,2 Yi Tian,2 Jing Chen,3 Xuan Lin1 1Department of Endocrinology, CR & WISCO General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3Pediatric Department, Dawu County Traditional Chinese Medicine Hospital, Xiaogan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Chen; Xuan Lin, Email 490998572@qq.com; 854964946@qq.comPurpose: The anti-tumor effects of Dendrobium officinale, as a medicinal and dietary Chinese medicine, have long been documented. However, the mechanism of action for its therapeutic effect has not been fully elucidated.Methods: The chemical constituents of Dendrobium officinale were screened using PubMed, CNKI, and Wanfang databases. Swiss Target Prediction was used to predict ingredient targets, while liver cancer targets were obtained from multiple databases. Venny 2.1.0 software identified intersection genes between the drug and disease, and a Protein–Protein Interaction (PPI) network was constructed. The DAVID database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Following this, the compound molecules were docked onto the core targets, and a visual analysis was conducted. The network pharmacology results were experimentally validated through in vitro studies with HepG2 cells.Results: The study identified 17 core components and 374 ingredient targets, with 1,249 disease targets collected from databases, yielding 50 overlapping targets. GO analysis revealed 284 Biological Process (BP) terms, 38 Cellular Component (CC) terms, and 75 Molecular Function (MF) terms. KEGG enrichment highlighted key pathways, including Pathways in cancer, PI3K-AKT signaling, Prostate cancer, and Proteoglycans in cancer. Molecular docking showed strong activity of Butin, Skimmin, and N-p-Coumaroyltyramine with core targets AKT1, EGFR, and CCND1. In vitro experiments demonstrated that Dendrobium officinale aqueous extracts significantly inhibited HepG2 cell proliferation. Western blotting analysis further revealed that the extracts downregulated the expression levels of p-PI3K, PI3K, AKT1, EGFR, and CCND1 proteins.Conclusion: The key active components of Dendrobium officinale in treating liver cancer include butin, skimmin, and N-p-coumaroyltyramine, etc. The specific mechanism of action may be related to the modulation of targets such as p-PI3K/PI3K, AKT1, EGFR, and CCND1, and signaling pathways such as PI3K-Akt.Keywords: Dendrobium officinale, liver cancer, network pharmacology, molecular docking, in vitro experiments |