Phytochemical Composition, Antioxidant Activity, Cytotoxicity, And Antidiabetic Potential of Ethanol Extract of Momordica charantia Using Insulin-Resistant HepG2 Cell Lines

Abstract

The therapeutic potential of plant-derived bioactive compounds is increasingly recognized in the management of diabetes mellitus. This study investigated the phytochemical profile, antioxidant capacity, cytotoxicity, and antidiabetic activity of the ethanol extract of Momordica charantia using insulin-resistant HepG2 cell lines using appropriate standard methods. Qualitative and quantitative phytochemical analyses revealed the presence of multiple bioactive constituents, with tannins (92.97 ± 0.21 mg/100 g) as the most abundant, followed by saponins (56.87 ± 0.01 mg/100 g) and phenols (50.56 ± 0.01 mg/100 g), while anthraquinones were present at the lowest concentration (8.88 ± 0.73 mg/100 g). GC–MS profiling identified fifteen compounds, predominantly n-hexadecanoic acid (42.19%), neophytadiene (11.18%), and octadecanoic acid (9.75%). The extract exhibited appreciable antioxidant activity, as evidenced by ferric reducing power and effective scavenging of DPPH and nitric oxide radicals, with IC₅₀ values of 78.40 µg/mL, 63.18 µg/mL, and 42.78 µg/mL, respectively. Cytotoxicity evaluation demonstrated a high IC₅₀ value of 6183.52 µg/mL in HepG2 cells, indicating low cytotoxic potential. Additionally, the extract modulated insulin signaling by downregulating the expression of AKT, IRS, and PIP3 genes. Although these effects were less pronounced than those observed with metformin and did not fully restore normal gene expression, the results collectively suggest that Momordica charantia possesses significant antioxidant and antidiabetic properties, supporting its potential application as a complementary therapeutic agent in diabetes management.