Molecular Mechanisms of Nigella sativa- and Nigella sativa Exercise-Induced Cardiac Hypertrophy in Rats

BACKGROUND: In our lab, we demonstrated cardiac hypertrophy induced by long-term administration of Nigella sativa (Ns) with enhanced function. Therefore, we aim to investigate the molecular mechanisms of Ns-induced cardiac hypertrophy, compare it with that induced by exercise training, and explore any possible synergistic effect of these two interventions. METHOD: Twenty adult Wistar male rats were divided into control (C), Ns-fed (N.s.), exercise-trained (Ex.), Ns-fed exercise-trained (N.s.Ex.) groups. 800 mg/kg of Ns was administered orally to N.s. rats. Ex. rats were trained on a treadmill with speed 18 m/min and grade 32° for two hours daily, and the N.s.Ex. group underwent both interventions. After 8 weeks, Immunohistochemical slides of the left ventricles were prepared using rat growth hormone (GH), insulin-like growth factor I (IGF-I), angiotensin-II receptors 1 (AT-I), endothelin-I (ET-1), Akt-1, and Erk-1. Cell diameter and number of nuclei were measured. RESULTS: Cardiomyocyte diameter, number of nuclei, GH, and Akt were significantly higher in N.s, Ex., and N.s.Ex groups compared with the controls. IGF-I, AT-1, and ET-1 were significantly higher in Ex. rats only compared with the controls. Erk-1 was lower in N.s., Ex., and N.s.Ex. compared with the controls. CONCLUSION: We can conclude that Ns-induced cardiac hypertrophy is mediated by the GH-IGF I-PI3P-Akt pathway. Supplementation of Ns to exercise training protocol can block the upregulation of AT-I and ET-1. The combined N.s. exercise-induced cardiac hypertrophy might be a superior model of physiological cardiac hypertrophy and be used as a prophylactic therapy for athletes who are engaged in vigorous exercise activity.