Probing the mechanism of action (MOA) of Solanum nigrum Linn against breast cancer using network pharmacology and molecular docking

Abstract

AbstractSolanum nigrum Linn is a medicinal herb widely used in traditional Chinese medicine to treat ailments such as fever, inflammation and cancer. Although quite a few compounds have been isolated and characterized, its anticancer mechanism remains elusive. Thus, in this study, we used network pharmacology and molecular docking strategies to identify the major active ingredients in S. nigrum and reveal its putative mechanism against human breast cancer. Six compounds, quercetin, cholesterol, 3-epi-beta-sitosterol, diosgenin, medioresinol and solanocapsine, were identified to be the major active ingredients. Target identification and analysis showed that they regulate 80 breast cancer-related targets. Furthermore, network analysis showed that the six active ingredients regulate multiple pathways including ErbB signaling pathway and estrogen signaling pathway and genes AKT1(AKT serine/threonine kinase 1), ESR1(estrogen receptor 1), EGFR(epidermal growth factor receptor), SRC(proto-oncogene tyrosine-protein kinase Src), AR(androgen receptor) and MMP9(matrix metalloproteinase 9) are crucial genes involved in the regulations. Molecular docking implied that quercetin could form good binding with AKT1, EGFR, SRC and MMP9. Our current study suggests that the anticancer function of S. nigrum is likely via synergistic/additive effects of multiple active ingredients’ regulations of different signaling pathways. Further studies are warranted to establish the standard for S. nuigrum to be used as a CAM (complementary and alternative medicine) in breast cancer treatment and dissect its potential interactions with chemotherapy drugs.