Morin Modulates Key Targets and Pathways Associated with Gastric Cancer: Network Pharmacology, Molecular Docking, Molecular Dynamics, ADMET, and In‑Vitro Analysis

Gastric cancer (GC), widely known as stomach cancer, is a critical health concern across the world. It ranks among the world’s five most common cancer types and is third in terms of fatalities from tumour disease. Natural products have been renowned for millennia and are highly reputable as a fashionable supply of therapeutic agents. Morin is a natural flavonoid found in a range of plants within the Rosaceae, Fagaceae, and chiefly Moraceae families. Network pharmacology, molecular docking, molecular dynamics simulations, and an in vitro cytotoxicity study were conducted. We have identified the top 10 hub genes (PIK3R3, PIK3CA, PIK3CB, PIK3CD, PIK3R2, PLCG1, JAK2, IGF1R, ZAP70, ERBB4) from network pharmacology analysis. Further molecular docking analysis revealed that morin has high binding affinities to PIK3CD (-11.01 kcal/mol), ZAP70 (-10.72 kcal/mol), JAK2 (-10.53 kcal/mol), IGF1R (-9.99 kcal/mol), PIK3CA (-9.79 kcal/mol), and ERBB4 (-8.83 kcal/mol). Molecular dynamics simulations confirmed the binding stability of morin with proteins like JAK2, PIK3CA, and IGF1R. The MTT assay demonstrated a significant escalation in the cytotoxicity of AGS GC cells following treatment with higher concentrations of morin. From in silico study results, we identified key oncogenic targets of morin which mainly work through PI3K-Akt pathway of GC which can be used as a reference for further research. An in vitro cytotoxicity study revealed that morin effectively inhibits the proliferation of AGS GC cells.