Cardioprotective effects of Rooibos (Aspalathus linearis) against isoproterenol-induced hypertrophy in H9c2 cardiomyoblasts: Enhancing antioxidative and mitochondrial function

Abstract

Cardiovascular disease (CVD) is a global health threat associated with several risk factors, including systemic hypertension. Persistent elevation in blood pressure exerts significant stress on the left ventricle, which can lead to left ventricular hypertrophy and over time, progress to left ventricular failure. Most pharmacological treatments have long-term side effects and are costly, especially for patients who reside in low-resource settings. Therefore, there is a quest to identify adjuvant therapies that are more natural and affordable, to assist in managing CVD. This study aimed to evaluate the protective effects of Aspalathus linearis (Rooibos, RB) against isoproterenol-induced hypertrophy in H9c2 cardiomyoblasts. Cardiomyoblasts were exposed to either isoproterenol (50 μM, 24 h), RB (100 μg/mL, 24 h), co-treatment with isoproterenol (50 μM, 24 h) and control (2 % FBS media, 24 h). We conducted the following experiments: cell viability assay (MTT), cell size (light microscopy), antioxidant assays (SOD and CAT), lipid peroxidation assay (TBARS), Western blots, high-resolution respirometry and an ATP assay. Isoproterenol increased cell size, reduced cell viability, reduced the activities of SOD and CAT, increased oxidative stress via an increase in lipid peroxidation, reduced mitochondrial routine respiration, complex-I linked OXPHOS and the contribution of complex-II to the ETS via the S-pathway, and elevated complex-IV activity without negatively impacting ATP levels. Co-treatment with RB and isoproterenol reduced cell size, improved antioxidant enzyme activity, increased routine respiration, increased complex-I linked OXPHOS, and reduced the cytochrome-c response, while increasing the expression of total Akt and reducing total NFAT expression. Our data suggests that RB may be a potential adjuvant therapy in treating left ventricular hypertrophy. The protective effect of RB in this context is ascribed to its potent antioxidant action and rescuing effect on mitochondrial dysfunction.