Exploring the potential of Inula viscosa extracts for antioxidant, antiproliferative and apoptotic effects on human liver cancer cells and a molecular docking study

In folk medicine, Inula viscosa (Asteraceae) has been traditionally utilized for treating various ailments, including diabetes, bronchitis, diarrhea, rheumatism, and injuries. In this study, we aimed to investigate the chemical composition, antioxidant, antiproliferative, and apoptotic properties of I. viscosa leaf extracts. Extraction was performed using solvents of varying polarities. Antioxidant activity was determined using Ferric reducing anti¬oxidant power (FRAP) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. The results reve¬aled that aqueous ethanol (70%) and aqueous ethyl acetate (70%) extracts contained high levels of phenols (645.58±8.77 mg CE/g) and flavonoids (180.69±1.54 mg QE/g), respectively. Aqueous ethanol (70%) extract exhibited the highest antioxidant activity with IC50 of 572.74 μmol TE/g DW (μmol Trolox equivalent in 1g of dry extract) in the ABTS assay and 76862.06 μM TE/g DW in the FRAP test. All extracts showed a considerable dose-dependent cytotoxic effect on cancerous HepG2 cells (P < 0.05). The aqueous ethanol extract demonstrated the highest inhibitory effect (IC50 = 1.67 mg/ml). Treatment with aqueous ethanol (70%) and pure ethyl acetate extracts significantly increased the number of apoptotic cells to 8 and 6%, respectively, in HepG2 cells (P < 0.05). Additionally, the aqueous ethanol extract significantly elevatedreactive oxygen species (ROS) levels (53%) in HepG2 cells. The molecular docking study identified paxanthone and banaxanthone E as the compounds that exhibited the highest binding affinities with BCL-2. This study demonstrated the potent antioxidant, antiproliferation, and intracellular ROS production of I. viscosa leaf extracts. Further studies should be conducted to identify the active compounds involved.