FasL and cytochrome c-induced apoptosis in cardiac tissue of hypertensive rats treated with Rhodomyrtus tomentosa

Context: Hypertensive heart disease is a leading cause of cardiovascular mortality worldwide. Cardiomyocyte apoptosis, mediated through intrinsic (cytochrome c) and extrinsic (Fas ligand, FasL) pathways, plays a critical role in the progression of hypertensive cardiac injury. Rhodomyrtus tomentosa, a medicinal plant rich in flavonoids and polyphenols, exhibits antioxidant and anti-inflammatory properties and may offer cardioprotective benefits. Aims: To evaluate the effects of R. tomentosa on FasL- and cytochrome c-mediated apoptosis in cardiac tissue of hypertensive rats. Methods: Hypertension was induced in male Wistar rats using L-NAME (40 mg/kg BW/day) for 28 days. Rats were divided into six groups: J− (normal control), J+ (L-NAME only), J0 (enalapril 2 mg/kg BW), and J1–J3 (L-NAME + R. tomentosa at 100, 200, and 300 mg/kg BW/day, respectively). Heart tissues were collected for histopathological and immunohistochemical analysis of FasL, cytochrome c, and caspase-3 expression. Serum levels of MDA, NGAL, and SOD were also measured. Results: R. tomentosa significantly reduced myocardial damage, apoptosis marker expression, and oxidative stress in a dose-dependent manner (p<0.01). The 300 mg/kg BW dose (J3) showed effects comparable to enalapril, including marked reductions in FasL, cytochrome c, and caspase-3 levels. Conclusions: R. tomentosa exerts cardioprotective effects by modulating both intrinsic and extrinsic apoptotic pathways and attenuating oxidative damage in hypertensive heart tissue. These findings support its potential as a natural adjunctive therapy for hypertensive cardiac injury.