Vafa Baradaran Rahimi1, Vahid Reza Askari2, Seyed Hadi Mousavi3. 1. Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 3. Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: mousavih@mums.ac.ir.
Abstract
AIMS: The world's population is becoming aged and the proportion of older persons is growing in almost every country in the world. Ellagic acid (EA) shows abundant pharmacological properties. Therefore, we aimed to determine the mechanism of anti-aging effects of low and high doses of EA. MAIN METHODS: Aging model was induced by d-galactose (DG), and the anti-aging effect of EA alone or in the presence of PPAR-γ antagonist GW9662, and in combination with metformin were evaluated. The activities of ALT, AST, and AChE, the levels of FBS, HbA1c, testosterone and DHEA-SO4, MDA, GSH, TNF-α, IL-6, advanced glycation end products (AGEs), and BDNF were measured in serum, liver or brain. KEY FINDINGS: DG led to increasing in the levels of IL-6, TNF-α, MDA, AChE, AGEs, ALT, AST, FBS, and HbA1c, in which decrease in the levels of body weight, GSH, BDNF, DHEA-SO4 and testosterone. Metformin (300 mg/kg) abrogated the effects of DG-induced aging model. We also found that the low dose of EA (30 mg/kg) decreases the deteriorative effects of DG-induced aging at 10 weeks of treatment only, however, high dose of EA (100 mg/kg) was effective at both 6 and 10 weeks of treatment. The addition of GW9662 completely reversed the effects of the low dose of EA, but not for the high dose, on DG-induced aging model. SIGNIFICANCE: We revealed that daily and oral administration of EA provides anti-aging effects at low dose in a PPAR-γ receptor-dependent fashion, but not at the high dose.
AIMS: The world's population is becoming aged and the proportion of older persons is growing in almost every country in the world. Ellagic acid (EA) shows abundant pharmacological properties. Therefore, we aimed to determine the mechanism of anti-aging effects of low and high doses of EA. MAIN METHODS: Aging model was induced by d-galactose (DG), and the anti-aging effect of EA alone or in the presence of PPAR-γ antagonist GW9662, and in combination with metformin were evaluated. The activities of ALT, AST, and AChE, the levels of FBS, HbA1c, testosterone and DHEA-SO4, MDA, GSH, TNF-α, IL-6, advanced glycation end products (AGEs), and BDNF were measured in serum, liver or brain. KEY FINDINGS: DG led to increasing in the levels of IL-6, TNF-α, MDA, AChE, AGEs, ALT, AST, FBS, and HbA1c, in which decrease in the levels of body weight, GSH, BDNF, DHEA-SO4 and testosterone. Metformin (300 mg/kg) abrogated the effects of DG-induced aging model. We also found that the low dose of EA (30 mg/kg) decreases the deteriorative effects of DG-induced aging at 10 weeks of treatment only, however, high dose of EA (100 mg/kg) was effective at both 6 and 10 weeks of treatment. The addition of GW9662 completely reversed the effects of the low dose of EA, but not for the high dose, on DG-induced aging model. SIGNIFICANCE: We revealed that daily and oral administration of EA provides anti-aging effects at low dose in a PPAR-γ receptor-dependent fashion, but not at the high dose.