School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, 510006, P.R. China and Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou University of Chinese Medicine, Guangzhou, 510006, P.R. China.
Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510120, P.R. China.
Food Funct. 2016 Nov 9;7(11):4545-4555. doi: 10.1039/c6fo01057a.
Accumulating evidence has shown that chronic injection of d-galactose (d-gal) can mimic natural aging, with accompanying liver and brain injury. Oxidative stress and apoptosis play a vital role in the aging process. In this study, the antioxidant ability of polydatin (PD) was investigated using four established in vitro systems. An in vivo study was also conducted to investigate the possible protective effect of PD on d-gal-induced liver and brain damage. The results showed that PD had remarkable in vitro free radical scavenging activity on 2,2-diphenyl-1-picryl-hydrazyl (DPPH˙), 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) (ABTS˙) radical ions, and hydroxyl and superoxide anions. Results in vivo indicated that, in a group treated with d-gal plus PD, PD remarkably decreased the depression of body weight and organ indexes, reduced the levels of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and alleviated alterations in liver and brain histopathology. PD also significantly decreased the level of MDA and elevated SOD, GSH-Px, CAT activity and T-AOC levels in the liver and brain. In addition, the levels of inflammatory mediators, such as TNF-α, IL-1β and IL-6 in serum were markedly reduced after PD treatment. Western blotting results revealed that PD treatment noticeably attenuated the d-gal-induced elevation of Bcl-2/Bax ratio and caspase-3 protein expression in liver and brain. Overall, our findings indicate that PD treatment could effectively attenuate d-gal-induced liver and brain damage, and the mechanism might be associated with decreasing the oxidative stress, inflammation and apoptosis caused by d-gal. PD holds good potential for further development into a promising pharmaceutical candidate for the treatment of age-associated diseases.
已有大量证据表明，慢性注射半乳糖（d-gal）可模拟自然衰老，同时伴有肝和脑损伤。氧化应激和细胞凋亡在衰老过程中起着至关重要的作用。在这项研究中，使用四种已建立的体外系统研究了虎杖素（PD）的抗氧化能力。还进行了一项体内研究，以研究 PD 对 d-gal 诱导的肝和脑损伤的可能保护作用。结果表明，PD 对 2,2-二苯基-1-苦基肼基（DPPH˙）、2,2'-联氮-双（3-乙基苯并噻唑啉-6-磺酸）（ABTS˙）自由基离子以及羟基和超氧阴离子具有显著的体外自由基清除活性。体内结果表明，在 d-gal 加 PD 处理组中，PD 显著降低了体重和器官指数的下降，降低了血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平，并缓解了肝和脑组织病理学的改变。PD 还显著降低了 MDA 水平，提高了 SOD、GSH-Px、CAT 活性和 T-AOC 水平在肝脏和大脑中。此外，PD 处理后血清中炎症介质 TNF-α、IL-1β和 IL-6 的水平明显降低。Western blot 结果表明，PD 处理可明显减弱 d-gal 诱导的肝和脑中 Bcl-2/Bax 比值和 caspase-3 蛋白表达的升高。总的来说，我们的研究结果表明，PD 治疗可有效减轻 d-gal 诱导的肝和脑损伤，其机制可能与降低 d-gal 引起的氧化应激、炎症和细胞凋亡有关。PD 具有成为治疗与年龄相关疾病的有前途的药物候选物的巨大潜力。
