Mitochondrial biogenesis and apoptosis as underlying mechanisms involved in the cardioprotective effects of Gallic acid against D-galactose-induced aging.

Abstract

Aging is a main risk factor for the development of cardiovascular diseases (CVDs). Gallic acid (GA) is a phenolic compound derived from a wide range of fruits. GA has a wide spectrum of pharmacological properties, including anti-oxidative, anti-inflammatory, and cardioprotective effects. This research was conducted to determine the cardioprotective effect of GA on cardiac hypertrophy in aged rats. Following histological evaluation and through observing the heart, we found that GA improved the cardiac hypertrophy induced by D-galactose (D-GAL) in cardiac cells. To clarify the causes for this anti-aging effect, we evaluated the malonic dialdehyde levels and antioxidant enzyme activity in rat cardiac tissue. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK-MB) in serum were measured. The levels of genes related to mitochondrial biogenesis, mitophagy, and apoptosis in cardiac tissue were surveyed. The findings represented that GA ameliorated antioxidant enzyme activity while significantly decreasing the malonic dialdehyde levels. Real-time PCR analysis proposed that GA effectively improved mitochondrial biogenesis in the heart via regulating the expression levels of Sirtuin 1 (SIRT1), PPARγ coactivator 1α (PGC1-α), nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial transcription factor A (TFAM). GA also mitigated apoptosis in the heart by modulating the expression levels of B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-associated X (Bax). In addition, GA improved serum LDH and CK-MB levels. GA may alleviate aging-induced cardiac hypertrophy via anti-oxidative, mitoprotective, and anti-apoptotic mechanisms.