Li Zipeng, Sun Ao, Wang Xin, Abulimiti Munila, Li Zhongtang, Li Zhongjun
The State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.
The State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China; Ningbo Institute of Marine Medicine, Peking University, Ningbo, 315832, PR China.
Carbohydr Res. 2024 Aug;542:109174. doi: 10.1016/j.carres.2024.109174. Epub 2024 Jun 9.
A series of derivatives of salidroside with mirror isomer glucose and different phenyl moieties were synthesized by Schmidt glycosylation in satisfactory yields, and their antioxidant and anti-inflammatory activities were evaluated by using LPS-induced RAW264.7 cells. One of the synthesized derivatives ʟ-Sal-4, bearing ʟ-glycosyl and -OMe modification at the phenyl ring, exhibited high activity in inhibiting the production of pro-inflammatory cytokines and oxidative stress biomarker MDA as well as in enhancing the activity of SOD enzyme, compared with the natural product and its corresponding ᴅ-enantiomer. Further proteomic analysis suggested that ʟ-Sal-4 exerted its anti-inflammatory activity through metabolic reprogramming. The in vitro activity showed that ʟ-Sal-4 is a potent antioxidant and anti-inflammatory agent. Our finding indicated that the ʟ-glucose-derived salidroside might be a promising lead compound in the development of salidroside derivatives as therapeutic agents.
通过施密特糖基化反应以令人满意的产率合成了一系列具有镜像异构体葡萄糖和不同苯基部分的红景天苷衍生物，并使用脂多糖诱导的RAW264.7细胞评估了它们的抗氧化和抗炎活性。合成的衍生物之一ʟ-Sal-4在苯环上带有ʟ-糖基和-OMe修饰，与天然产物及其相应的ᴅ-对映体相比，在抑制促炎细胞因子的产生和氧化应激生物标志物丙二醛方面表现出高活性，同时在增强超氧化物歧化酶（SOD）的活性方面也表现出色。进一步的蛋白质组学分析表明，ʟ-Sal-4通过代谢重编程发挥其抗炎活性。体外活性表明，ʟ-Sal-4是一种有效的抗氧化剂和抗炎剂。我们的研究结果表明，源自ʟ-葡萄糖的红景天苷可能是开发作为治疗剂的红景天苷衍生物的有前途的先导化合物。
