Attenuation of Angiotensin II- Induced Cardiomyocyte Hypertrophy by Moringa oleifera Lam. extract, Fractions and Bioactive Constituents: Cell Size Analysis and Molecular Docking

OBJECTIVE Moringa oleifera Lam. leaves are valued for their rich nutritional profile and traditional use in treating various ailments, including hypertension. However, research focusing on their mechanism of action, particularly their interactions with angiotensin (Ang) II receptors remains limited. This study aimed to evaluate the effects of M. oleifera leaves extract, fractions and bioactive compounds (kaempferol, chlorogenic acid, gallic acid, and vicenin-2) on Ang II induced H9c2 cells and their binding affinities toward Ang II receptors. METHOD The crude extract was fractionated into hexane, dichloromethane, ethyl acetate, acetone and methanol fractions. Cell viability test was carried out and concentrations that maintained cell viability at 80% and more were selected for further study. Hypertrophic model was simulated by inducing H9c2 cells with Ang II (1 µM) and the antihypertrophic effect was assessed by measuring changes in the cell size. RESULTS Ang II significantly doubled the cell size compared to normal control groups. Results showed that the crude extract, its ethyl acetate, acetone, and methanol fractions, and bioactive compounds significantly reduced Ang II-induced cell hypertrophy (p < 0.05) in H9c2 cells compared to the Ang II untreated group. Furthermore, bioactive compounds tested also showed significant dose-dependent (10, 20, and 40 µM) reduction in cell size compared to the Ang II group. Gallic acid demonstrated the highest potency by reducing the size the most at the highest dose tested (40 µM), followed by quercetin, chlorogenic acid, vicenin and kaempferol. In molecular docking studies, binding energies of -5.5 kcal/mol and lower were recorded for all bioactive compounds indicating their strong binding affinities toward Ang II receptor. CONCLUSION This work provides an evaluation of Ang II-induced cardiomyocyte hypertrophy attenuation activity of bioactive compounds identified in the M. oleifera leaves extract. These findings serve as a foundation for future studies aimed at developing therapies for cardiovascular diseases from natural resources.