Research on Anti-Gastric Cancer Activity of Panax japonicus var. major and Related Main Functional Compounds

Background/Objectives: Gastric cancer is a common malignant tumor worldwide, and few natural substances are available for its effective treatment. The ginseng Panax japonicus var. major is a natural medicinal plant with anticancer properties in terms of traditional knowledge of indigenous peoples in Yunnan of SW China. Methods: In this study, we employed network pharmacology, molecular docking, untargeted metabolomics and molecular dynamics simulations to predict the mode of action of active compounds from P. japonicus var. major in the treatment of gastric cancer. In vitro experiments and Western blot validation were conducted to validate these predictions. Results: Screened 44 main compounds which chikusetsu saponin IVa and calenduloside E inhibit the growth of gastric cancer cells) from P. japonicus var. major and explored 29 core decease targets which include four core targets (CASP3, TNF, AKT1, EGFR) of gastric cancer through two (TNF and T-cell receptor) signaling pathways. It is important that we not only found that the CASP3 and Chikusetsu saponin IVa formed a structurally stable complex with strong binding via multiple hydrogen bonds, but also revealed that both exert anti-gastric cancer effects by downregulating the Bcl-2/Bax ratio and upregulating the expression of CASP3 and CASP9 proteins, and provided the significant difference in anti-gastric cancer activity between two extracts from fresh and dried P. japonicus var. major. Conclusion: This results may provide a scientific supportting for indigenous medicine usage of P. japonicus var. major for gastric cancer treating and need further Pharmacological experiments and clinical experiments.