Mitochondrial biogenesis as an underlying mechanism involved in the cardioprotective effects of Gallic acid against D‐galactose-induced aging

Abstract

Aged heart is defined via structural and mitochondrial dysfunction of the heart. However, there is still no impressive compound to suppress and improve the abnormal alterations in cardiac function result from aging. Gallic acid (GA) is known to be an effective agent in improving cardiovascular disorders. In the present study, we exhibit the protective effects of GA against cardiac aging. Male Wistar rats were randomly divvied into four groups: Control, Control treated with GA at 25 mg/kg (GA25), aged rats induced by D-galactose (D-GAL), aged rats treated with GA at 25 mg/kg (D-GAL + GA25).Aging induced by D-GAL at 150 mL/kg via intraperitoneal injection for eight weeks. Aged rats treated with GA at 25 mg/kg (D-GAL GA25) by gavage for eight weeks. The blood samples were used to assessment biochemical factors and heart tissue was assessed for evaluating oxidative stress and the gene expression of molecular parameters. Histological examination of the heart was occurred. The D-GAL rats indicated cardiac hypertrophy, which was associated with reduced antioxidant activity of enzyme, increased oxidative marker and alterations in Sirtuin 1 (SIRT1), Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha and Transcription Factor A, Mitochondrial (TFAM) genes expression in comparison to the control animals. Co-treatment with GA improved all these alterations. Taken together, GA could protect the heart against D-GAL-induced aging via antioxidant effects, and the enhancement of SIRT1, PGC-1α, and TFAM genes expression.

The changes of cardiac energy metabolism with sodium-glucose transporter 2 inhibitor therapy

“…Mitochondrial biogenesis is characterized by generating new mitochondria and increasing mitochondrial content and number. Alterations in the mitochondria fusion and fission processes as well as mitophagy suppression might lead to a decrease in mitochondrial biogenesis (141). PGC1-α is a vital transcriptional regulator of mitochondrial biogenesis and can activate the transcriptional expression of nuclear respiratory factor-1/2 (NRF-1/2).…”

“…Acting as an upstream factor, SIRT1 directly stimulated PGC1-α expression (145, 146). Zarei et al observed that stimulating the SIRT1/PGC1-α pathway reduced the cardiomyocytes toxicity of D-galactose-induced by improving mitochondrial biogenesis (141). According to Santos-Gallego et al, Empagliflozin therapy enhanced heart function and mitochondria energetics in porcine model of HF, which was achieved by upregulating the expression of AMPK and PGC-1α (15).…”