Elucidating the Mechanism of Oridonin in Treating Hepatocellular Carcinoma: Network Pharmacology and Experimental Validation.

Oridonin, a bioactive diterpenoid derived from Rabdosia rubescens, has significant anti-tumour activity. Although previous studies have shown that oridonin has anti-liver cancer potential, the molecular mechanism of its treatment of hepatocellular carcinoma (HCC) still needs to be further investigated. This study utilized network pharmacology, molecular docking, and molecular dynamics simulations (MDS) to elucidate the mechanisms by which oridonin exerts its therapeutic effects on HCC. The findings were then validated by in vitro experiments. Initially, potential targets of oridonin for HCC were identified through online database retrieval. The mechanisms of oridonin in resisting HCC were then elucidated via integrated protein-protein interaction (PPI) network analysis, GO and KEGG enrichment analysis. Subsequently, these findings were confirmed through molecular docking, MDS and the in vitro experiments. A total of 273 intersecting targets were identified. Subsequently, PPI network analysis was performed, leading to the identification of 10 core targets. Molecular docking studies between these targets and oridonin suggested that PIK3R1, EGFR, AKT1, and JAK2 might be key targets. Further MDS demonstrated a strong interaction between oridonin and these key targets. Subsequent in vitro experiments revealed that oridonin significantly affects the cell cycle and induces apoptosis in HCC cells. Furthermore, oridonin significantly inhibits the expression of key targets within the EGFR/PI3K/AKT signalling pathway. These findings suggest that oridonin may exert anti-cancer effects through the EGFR/PI3K/AKT signalling pathway, providing a robust theoretical foundation for its clinical application and mechanistic investigation in HCC treatment.