Network pharmacology-based study on apigenin present in the methanolic fraction of leaves extract of Cestrum nocturnum L. to uncover mechanism of action on hepatocellular carcinoma.

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer in the world. It is the third leading cause of cancer-related mortality. In more than 80% of people liver cancer-related death is due to its poor prognosis. The flavonoids obtained from natural sources have potent therapeutic effects on HCC. The flavonoid rich methanolic fraction obtained from ethyl acetate extract of leaf of Cestrum nocturnum (MFLCN) was analyzed by UPLC-QTOFMS/MS for the presence of different flavonoids. The physiochemical and pharmacokinetics properties of the identified flavonoids were performed by absorption, distribution, metabolism, excretion, and toxicity (ADMET). It was selected on the basis of Lipinski rule and hepatotoxicity evaluations. The potential gene dataset of HCC were taken from gene card database and targets compounds were selected from target net prediction. Gene ontology and pathway enrichment analysis of HCC was performed via enricher and David web tools. Cytoscape was used to visualize targets and network pathways. MFLCN contains 33 flavonoids. Among these flavonoids, apigenin was selected as principal active compound on the basis of their pharmacokinetic and ADMET properties. Apigenin has 92 targets out of 627 total targets related to HCC, while there was13 pathways in the target-pathway network. Results revealed that apigenin regulates cell proliferation and survival, primarily through different signaling pathways like estrogen, VEGF, PI3K/AKT1, TNF, FoXO, and Ras signaling pathways. Thus, integrating network pharmacology prediction with m-RNA and human protein atlas validation could be an effective method for understanding the molecular mechanism of apigenin on HCC.