Mukia maderaspatana (L.) M. Roem. phytoconstituents: Unveiling their anticancer potentials against hepatocellular carcinoma cells

Abstract

Globally, hepatocellular carcinoma poses significant health challenges due to its higher incidence and mortality rates. Further adverse effects of synthetic drugs prompted research into herbal plants as safer, more effective and alternative treatments. Mukia maderaspatana (L.) M. Roem. is a traditional medicinal renowned for its therapeutic properties. This study explores the anticancer property of hydroalcoholic leaf extract of M. maderaspatana (HLEMM) against liver carcinoma (HepG2) cells and further unveils the active phytoconstituents. Purification and characterization of HLEMM through spectroscopic analysis (HPLC, UV-Vis, MS, FT-IR, NMR) evidenced 3,3′,4′,5,5′,7–Hexahydroxyflavone (Myricetin) as the active phytoconstituent. Cytotoxicity of HLEMM on HepG2 cells showed a significantly dose-dependent reduction in cell viability with an IC50 of 128.6 ± 0.4 μg/ml. Cell cycle analysis revealed that HLEMM effectively inhibited HepG2 cells at the G2/M phase. Results of the Annexin-V/PI staining study inferred HLEMM-induced apoptosis in the early and late phases of HepG2 cells. Flow cytometry results confirmed the up-regulation of caspase-3 and caspase-9 along with the simultaneous down regulation of Bcl-2, substantiating the activation of apoptosis, a controlled process of programmed cell death due to cellular stress or damage. Depolarization of the mitochondrial membrane in HepG2 cells was confirmed by a decrease in JC-1 fluorescence, as observed under a confocal fluorescent microscope. This tends to indicate the alteration in membrane potential and interference in energy metabolites. In silico biodegradability pattern of Myricetin by BIOWINTM models showed its rapid biodegradation under aerobic conditions and further emphasized its environmental sustainability. In conclusion, this is the first report spotlighting Myricetin as the active compound from M. maderaspatana and further suggests that it could serve as a potential anti-cancer agent for treating liver cancer.