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圣草次苷通过抑制 Nrf2 介导的氧化应激和调节肠道微生物群延缓 D-半乳糖诱导的衰老进程在小鼠体内。

Taxifolin retards the D-galactose-induced aging process through inhibiting Nrf2-mediated oxidative stress and regulating the gut microbiota in mice.

机构信息

College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.

College of Traditional Chinese Medicine, Jilin Agricultural Science and Technology University, Jilin 132101, China.

出版信息

Food Funct. 2021 Nov 29;12(23):12142-12158. doi: 10.1039/d1fo01349a.

DOI:10.1039/d1fo01349a
PMID:34788354
Abstract

Aging and aging-related metabolic complications are global problems that seriously threaten public health. Taxifolin (TAX) is a novel health food and has been widely proved to have a variety of biological activities used in food and medicine. However, the delayed effect of TAX on the aging process has not been investigated. The purpose of this study is to explore the role of TAX as a natural active substance on aging brain tissue induced by D-galactose (D-Gal) and to determine the effect of supplementing TAX on the metabolism of the intestinal flora in aging bodies. The aging model was established by intraperitoneal injection of D-Gal (800 mg kg) once per 3 days for 12 weeks, and TAX (20 and 40 mg kg) was administered daily by oral gavage after 6 weeks of induction with D-Gal. After testing aging mice in an eight-arm maze, the results showed that TAX treatment significantly restored spatial learning and memory impairment. Moreover, long-term D-Gal treatment incited cholinergic dysfunction of aging mice, and H&E staining revealed obvious histopathological damage and structural disorder in the hippocampus of mouse brain tissue, while TAX treatment significantly reversed these changes. Importantly, supplementing with TAX significantly mitigated oxidative stress injury by alleviating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) while increasing antioxidant enzymes. Furthermore, TAX decreased the apoptosis of the aging brain by regulating the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and activating nuclear factor-erythroid 2-related factor 2 (Nrf2), nuclear heme oxygenase-1 (HO-1), and NADH dehydrogenase quinone 1 (NQO1) to maximally moderate the oxidative stress injury that occurred after D-Gal induction. In addition, 16S rDNA analysis revealed that TAX treatment decelerated the D-gal-induced aging process by regulating the composition of the intestinal flora and abundance of beneficial bacteria, including , , , and . In conclusion, the results of this study demonstrated that TAX alleviated oxidative stress injury in mice aged by D-Gal and also confirmed that TAX improved the aging process by regulating intestinal microbes, which provides the possibility of prevention and treatment for aging and metabolic disorders through the potential food health factors.

摘要

衰老是一个全球性的问题,与衰老相关的代谢并发症严重威胁着公众健康。云实素(TAX)是一种新型的保健品,已被广泛证明具有多种生物活性,可用于食品和医药。然而,TAX 对衰老过程的延迟作用尚未得到研究。本研究旨在探讨 TAX 作为一种天然活性物质对 D-半乳糖(D-Gal)诱导的衰老脑组织的作用,并确定补充 TAX 对衰老机体肠道菌群代谢的影响。通过腹腔注射 D-Gal(800mg/kg),每 3 天一次,共 12 周建立衰老模型,在 D-Gal 诱导 6 周后,每日通过口服灌胃给予 TAX(20 和 40mg/kg)。在八臂迷宫中对衰老小鼠进行测试后,结果表明 TAX 治疗可显著恢复空间学习和记忆障碍。此外,长期 D-Gal 处理会引发衰老小鼠的胆碱能功能障碍,H&E 染色显示小鼠脑组织海马区明显的组织病理学损伤和结构紊乱,而 TAX 治疗可显著逆转这些变化。重要的是,补充 TAX 通过减轻活性氧(ROS)和丙二醛(MDA)水平,同时增加抗氧化酶,显著减轻氧化应激损伤。此外,TAX 通过调节磷酸化水平来减少衰老大脑的凋亡磷脂酰肌醇 3-激酶(PI3K)、蛋白激酶 B(AKT)和核因子-红细胞 2 相关因子 2(Nrf2)、核血红素氧合酶-1(HO-1)和 NADH 脱氢酶醌 1(NQO1),最大程度地缓解 D-Gal 诱导后发生的氧化应激损伤。此外,16S rDNA 分析表明,TAX 通过调节肠道菌群的组成和有益菌的丰度来减缓 D-gal 诱导的衰老过程,包括、、、和。总之,本研究结果表明,TAX 减轻了 D-Gal 诱导的衰老小鼠的氧化应激损伤,同时证实 TAX 通过调节肠道微生物改善衰老过程,为通过潜在的食物健康因素预防和治疗衰老和代谢紊乱提供了可能性。

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