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.
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.
Life Sci. 2019 Sep 1;232:116595. doi: 10.1016/j.lfs.2019.116595. Epub 2019 Jun 22.
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.
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-SO, MDA, GSH, TNF-α, IL-6, advanced glycation end products (AGEs), and BDNF were measured in serum, liver or brain.
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.
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.
世界人口正在老龄化，几乎每个国家的老年人比例都在增长。鞣花酸 (EA) 表现出丰富的药理特性。因此，我们旨在确定低剂量和高剂量 EA 的抗衰老作用机制。
使用半乳糖 (DG) 诱导衰老模型，评估 EA 单独或与 PPAR-γ 拮抗剂 GW9662 以及与二甲双胍联合使用的抗衰老作用。测量血清、肝脏或大脑中的 ALT、AST 和 AChE 活性、FBS、HbA1c、睾酮和 DHEA-SO 水平、MDA、GSH、TNF-α、IL-6、晚期糖基化终产物 (AGEs) 和 BDNF。
DG 导致 IL-6、TNF-α、MDA、AChE、AGEs、ALT、AST、FBS 和 HbA1c 水平升高，体重、GSH、BDNF、DHEA-SO4 和睾酮水平降低。二甲双胍 (300mg/kg) 阻断了 DG 诱导的衰老模型的作用。我们还发现，低剂量 EA (30mg/kg) 仅在治疗 10 周时降低 DG 诱导的衰老的恶化作用，而高剂量 EA (100mg/kg) 在治疗 6 和 10 周时均有效。GW9662 的添加完全逆转了低剂量 EA 对 DG 诱导的衰老模型的作用，但对高剂量 EA 没有作用。
我们揭示了每日和口服给予 EA 在 PPAR-γ 受体依赖性方式下在低剂量时具有抗衰老作用，但在高剂量时没有。
