Exploring the therapeutic mechanisms of Gleditsiae Spina acting on pancreatic cancer via network pharmacology, molecular docking and molecular dynamics simulation

Abstract

Pancreatic cancer is one of the most aggressive tumors and also has a low survival rate. The dried spines of Gleditsia sinensis Lam are known as “Gleditsiae Spina” and they mostly contain flavonoids, phenolic acids, terpenoids, steroids, and other chemical components. In this study, the potential active components and molecular mechanisms of Gleditsiae Spina for treating pancreatic cancer were systematically revealed by network pharmacology, molecular docking and molecular dynamics simulations (MDs). RAC-alpha serine/threonine-protein kinase (AKT1), cellular tumor antigen p53 (TP53), tumor necrosis factor α (TNFα), interleukin-6 (IL6) and vascular endothelial growth factor A (VEGFA) were common targets of Gleditsiae Spina, human cytomegalovirus infection signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and MAPK signaling pathway were critical pathways of fisetin, eriodyctiol, kaempferol and quercetin in the treatment of pancreatic cancer. Molecular dynamics simulations (MDs) results showed that eriodyctiol and kaempferol have long-term stable hydrogen bonds and high binding free energy for TP53 (−23.64 ± 0.03 kcal mol⁻¹ and −30.54 ± 0.02 kcal mol⁻¹, respectively). Collectively, our findings identify active components and potential targets in Gleditsiae Spina for the treatment of pancreatic cancer, which may help to explore leading compounds and potential drugs for pancreatic cancer.