Phytochemical analysis and in vitro anti-inflammatory, anticancer activities of Marrubium lutescens on melanoma cancer cell line and molecular docking studies

Abstract

Introduction: The use of plants and their derivatives in the search for new therapeutic agents is on the increase every day due to their versatile applications. Methods: Phytochemical analysis of Marrubium lutescens extract was carried out by liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS). Cytotoxicity of plant extract was determined by MTT assay on G361 cells. Moreover, the binding energetics of the two predominant compounds, rosmarinic acid and chlorogenic acid, against the target proteins microtubule affinity-regulating kinase 4 (MARK4) and human tyrosinase-related protein 1 (TYRP1) were also determined using molecular docking to gain molecular insights into the induced anti-cancer effect in G361. TAS, Total oxidant activity, and oxidative stress index of the cells lysates were determined. Also, TNF-alpha, TGF-j3, DEF-j32, IL-1j3 cytokine levels were determined. Results: Twenty distinct phytochemicals were determined and among the identified compounds, rosmarinic acid and chlorogenic acid as major components. Rosmarinic acid and chlorogenic acid have exhibited energetically highly favourable binding with intracellular target proteins MARK4 and TYRP1, as shown by their respective binding affinity values (Delta G = -7.97 kcal/mol; Delta G = -7.38 kcal/mol, respectively), suggesting further molecular evidence for the induced anti-cancer effect observed in the G361 cell line. Also, we have evaluated the anticancer prospective of M. lutescens. Anti-inflammatory mediators and oxidative stress parameters were increased to plant extract exposed cell line. Conclusions: Reported results show that plant extract shown anticancer activity on G361 cells. According to the docking results, rosmarinic acid and chlorogenic acid, the two predominant compounds identified in the extract, may be responsible for the anti-cancer effect through synergistic action via prominent inhibition of MARK4 and TYRP1.