Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China.
The Research Center of Allergy and Immunology, School of Medicine, Shenzhen University, Shenzhen, China.
Arch Pharm (Weinheim). 2019 Sep;352(9):e1900100. doi: 10.1002/ardp.201900100. Epub 2019 Jul 17.
The antioxidative effects of 30 xanthone derivatives (XDs) (XD-n, n = 1-30) in HepG2 cells were evaluated by the cellular antioxidant activity assay. Results showed that all XDs were antioxidants and 1,3,5,8-tetrahydroxy-9H-xanthen-9-one (XD-2) was the most active antioxidant. The all-oxygenated substituted xanthones extended the lifespan of wild-type N2 nematodes under normal culture conditions and XD-2 was the best one. XD-2 eliminated excessive intracellular reactive oxygen species and enhanced the expression levels and activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. XD-2 inhibited the H O -increased phosphorylation levels of c-JUN N-terminal kinase, extracellular signal-regulated kinase, and p38 in HepG2 cells. In vivo, XD-2 also extended the lifespan of wild-type N2 nematodes under oxidative stress induced by paraquat, but failed in extending the lifespan of CF1038 (daf-16 deletion) and AY102 (pmk-1 deletion) mutant nematodes. It was revealed by real-time polymerase chain reaction that the genes daf-16, sir-2.1, akt-1, and age-1 were all inhibited by paraquat stimuli, while XD-2 reversed these inhibitions; in contrast, paraquat stimuli upregulated both the skn-1 and pmk-1 genes. However, treatment by XD-2 further increased the levels of both genes. These pieces of evidence implied that XD-2 promotes longevity through endogenous signaling pathways rather than through the antioxidative activity alone. Taken all together, it may be concluded that XD-2 is a promising antiageing agent.
用细胞抗氧化活性测定法评估了 30 种二氢黄酮衍生物 (XDs) (XD-n，n = 1-30) 在 HepG2 细胞中的抗氧化作用。结果表明，所有 XDs 均具有抗氧化作用，1,3,5,8-四羟基-9H-呫吨-9-酮 (XD-2) 是最具活性的抗氧化剂。全氧取代的呫吨酮可延长正常培养条件下野生型 N2 线虫的寿命，其中 XD-2 效果最好。XD-2 可消除过多的细胞内活性氧，并增强抗氧化酶超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的表达水平和活性。XD-2 可抑制 H O 诱导的 HepG2 细胞中 c-JUN N-末端激酶、细胞外信号调节激酶和 p38 的过度磷酸化。体内，XD-2 也可延长百草枯诱导的氧化应激下野生型 N2 线虫的寿命，但对 CF1038(daf-16 缺失)和 AY102(pmk-1 缺失)突变体线虫的寿命无延长作用。实时聚合酶链反应显示，daf-16、sir-2.1、akt-1 和 age-1 等基因均受百草枯刺激抑制，而 XD-2 可逆转这些抑制作用；相反，百草枯刺激可上调 skn-1 和 pmk-1 基因。然而，XD-2 处理进一步增加了这两个基因的水平。这些证据表明，XD-2 通过内源性信号通路促进长寿，而不仅仅是通过抗氧化活性。综上所述，XD-2 可能是一种有前途的抗衰老药物。
