The Activity, Composition and Molecular Mechanism of Bothriospermum zeylanicum (Hornem.) Fisch. Et Mey Alleviation of Nonsmall Cell Lung Cancer

Abstract

Objective: To study the effect of the ethyl acetate extract of Bothriospermum zeylanicum (Hornem.) Fisch., the active ingredients and mechanism of Et Mey (EAF) in nonsmall cell lung cancer (NSCLC) were explored. Methods: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was used to measure the effect of EAF on the proliferation of A549, HL-60, SMMC-7721, MDA-MB-231, and SW480 tumor cells. The components were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS), and the blood components were retrieved from the constituents absorbed into the blood and metabolites of traditional Chinese medicine (DCABM-TCM) database. The mechanism was determined by network pharmacology and verified by molecular docking. Results: The IC50 values for the proliferation of tumor cell strains were 41.13, 56.72, 36.69, 48.63, and 44.48 μg/mL, respectively. A concentration of 100 μg/mL had the strongest inhibitory effect on A549 cells. A total of 33 chemical components were identified by LC-MS, 7 of which have been reported to have certain anti-NSCLC effects, and a total of 6 blood components were identified using the DCABM-TCM database. Network pharmacology analysis revealed that anti-NSCLC activity mainly involves EGFR tyrosine kinase inhibitor resistance, the PI3K-Akt signaling pathway, the AGE-RAGE signaling pathway in diabetic complications, the HIF-1 signaling pathway and the VEGF signaling pathway. The molecular docking results verified that hesperetin, luteolin, and pinocembrin bind well to the AKT1, IL6, EGFR, BCL2, and CASP3 target proteins. Conclusion: The ethyl acetate fraction of B. zeylanicum (Hornem.) Fisch. Et Mey had obvious ant-non NSCLC activity, which may be related to resistance to EGFR tyrosine kinase inhibitors and the PI3K-Akt signaling pathway in diabetic complications, and its active ingredients may be hesperetin, luteolin, and pinocembrin.