Anticancer potential, antioxidant activity, chemical content, and enzyme inhibitory properties of Inula aschersoniana Janka, supported by an integrated network pharmacology study

Abstract

This study explores the biological and pharmacological potential of Inula aschersoniana Janka (I. aschersoniana) by utilizing both in silico computational and in vitro analyses, focusing on anticancer, antioxidant, and enzyme inhibitory activities. I. aschersoniana extracts were observed to have effective properties against breast cancer (MCF-7) and human colon adenocarcinoma (HT-29) cell lines compared to normal human umbilical vein endothelial (HUVEC) cell line. Also, effective antioxidant activity of the plant sample was determined by using several in vitro antioxidant methods. Furthermore, inhibitory effects of I. aschersoniana extracts against alpha-glucosidase (alpha-Gly) and glutathione S-transferase (GST) enzymes were evaluated. The IC50 value of I. aschersoniana ethyl acetate extract was determined as 4.05 & micro;g/mL for alpha-Gly and 1.67 & micro;g/mL for GST. Similarly, IC50 value of the ethanol extract was measured as 3.74 & micro;g/mL for alpha-Gly and 2.71 & micro;g/mL for GST. Also, main organic compounds of I. aschersoniana were detected to be vanillic acid, rutin, and naringin by HPLC technique. Finally, integrated network pharmacology, molecular docking, and molecular dynamics simulations were performed to elucidate the potential interactions between the active components of I. aschersoniana and genes associated with breast and colon cancer. To ensure reliability, molecular docking results were validated using re-docking and comparison with reference inhibitors or co-crystallized ligands. RMSD and RMSF analyses revealed that naringin, the major compound of I. aschersoniana, exhibited dynamically stable binding within the active sites of AKT1, EGFR, and PPARG proteins, with AKT1@Naringin and PPARG@Naringin complexes displaying a more stable dynamic profile. In this network pharmacology study, forty-five common targets between the major compounds of I. aschersoniana with breast and colon cancers were identified.