College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, China.
Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, School of Environment and Health, Jianghan University, Wuhan, China.
Zebrafish. 2023 Apr;20(2):55-66. doi: 10.1089/zeb.2022.0045.
Population aging is a global problem worldwide, and the discovery of antiaging drugs and knowledge of their potential molecular mechanisms are research hotspots in biomedical field. Tetrahydroxystilbene glucoside (TSG) is a natural component isolated from Heshouwu ( Thunb.). It has been widely used to treat various chronic diseases for its remarkable biological activities. In this study, we successfully established aging larval zebrafish by exposing larvae to 2 mM hydrogen peroxide (HO). Using this aging model, we assessed the antiaging effect of TSG with different concentrations (25-100 μg/mL). After being treated with HO, zebrafish showed the obvious aging-associated phenotypes characterized by higher senescence-associated β-galactosidase activity, significantly downregulated expression of sirtuin 1 () and telomerase reverse transcriptase (), and upregulated mRNA level compared to the control group. TSG pretreatment delayed the aging process of oxidative stress-induced zebrafish, indicative of the reduced positive rate of senescence-associated β-galactosidase, improved swimming velocity, and stimulus-response capacity. Further studies proved that TSG could suppress reactive oxygen species production and enhance the activity of antioxidant enzymes superoxide dismutase and catalase. TSG also inhibited the HO-induced expressions of inflammation-related genes , , -, and - in aging zebrafish, but it did not affect apoptosis-related genes (, , and ) of aging zebrafish. In conclusion, TSG can protect against aging by regulating the antioxidative genes and enzyme activity, as well as inflammation in larval zebrafish, providing insight into the application of TSG for clinical treatment of aging or aging-related diseases.
人口老龄化是一个全球性问题，抗老化药物的发现及其潜在分子机制的研究是生物医学领域的热点。二苯乙烯苷（TSG）是从何首乌中分离得到的一种天然成分，由于其显著的生物学活性，已被广泛用于治疗各种慢性疾病。本研究通过向幼虫暴露于 2mM 过氧化氢（HO）成功建立了衰老的幼虫斑马鱼模型。使用这种衰老模型，我们评估了不同浓度（25-100μg/mL）的 TSG 的抗老化作用。在 HO 处理后，与对照组相比，斑马鱼表现出明显的与衰老相关的表型，衰老相关的β-半乳糖苷酶活性更高，sirtuin 1（）和端粒酶逆转录酶（）的表达显著下调，mRNA 水平上调。TSG 预处理可延缓氧化应激诱导的斑马鱼衰老过程，衰老相关β-半乳糖苷酶的阳性率降低，游泳速度提高，刺激反应能力增强。进一步的研究证明，TSG 可以抑制活性氧的产生并增强抗氧化酶超氧化物歧化酶和过氧化氢酶的活性。TSG 还抑制了 HO 诱导的衰老斑马鱼中炎症相关基因（、、-和-）的表达，但不影响衰老斑马鱼中与凋亡相关的基因（、、和）。综上所述，TSG 通过调节抗氧化基因和酶活性以及炎症反应，可以保护幼鱼免受衰老的影响，为 TSG 在临床治疗衰老或与衰老相关的疾病中的应用提供了新的思路。
