Isoschaftoside is a C-glycosyl flavonoid extracted from the root exudates of Desmodium uncinatum and Abrus cantoniensis. Previous studies suggested that C-glycosyl flavonoid has neuroprotective effects with the property of reducing oxidative stress and inflammatory markers. Microglia are key cellular mediators of neuroinflammation in the central nervous system. The aim of this study was to investigate the effect of isoschaftoside on lipopolysaccharide-induced activation of BV-2 microglial cells. The BV-2 cells were exposed to 10 ng/ml lipopolysaccharide and isoschaftoside (0–1000 μM). Isoschaftoside effectively inhibited lipopolysaccharide-induced nitric oxide production and proinflammatory cytokines including iNOS, TNF-α, IL-1β, and COX2 expression. Isoschaftoside also significantly reduced lipopolysaccharide-induced HIF-1α, HK2, and PFKFB3 protein expression. Induction of HIF-1α accumulation by CoCl₂ was inhibited by isoschaftoside, while the HIF-1α specific inhibitor Kc7f2 mitigated the metabolic reprogramming and anti-inflammatory effect of isoschaftoside. Furthermore, isoschaftoside attenuated lipopolysaccharide-induced phosphorylation of ERK1/2 and mTOR. These results suggest that isoschaftoside can suppress inflammatory responses in lipopolysaccharide-activated microglia, and the mechanism was partly due to inhibition of the HIF-1α-mediated metabolic reprogramming pathway.

中文翻译：

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异沙夫糖苷通过调节 HIF-1α 介导的代谢重编程抑制脂多糖诱导的小胶质细胞炎症

Isoschaftoside 是一种 C-糖基类黄酮，提取自Desmodium uncinatum和Abrus cantoniensis的根部分泌物。先前的研究表明，C-糖基类黄酮具有神经保护作用，具有减少氧化应激和炎症标志物的特性。小胶质细胞是中枢神经系统神经炎症的关键细胞介质。本研究的目的是研究异沙夫糖苷对脂多糖诱导的 BV-2 小胶质细胞活化的影响。BV-2 细胞暴露于 10 ng/ml 脂多糖和异沙夫糖苷 (0–1000  μ M)。异沙夫糖苷有效抑制脂多糖诱导的一氧化氮产生和促炎细胞因子，包括 iNOS、TNF - α、IL-1β和 COX2 表达。Isoschaftoside 还显着降低脂多糖诱导的 HIF-1 α、HK2 和 PFKFB3 蛋白表达。CoCl ₂诱导的 HIF-1 α积累被异沙夫糖苷抑制，而 HIF-1 α特异性抑制剂 Kc7f2 减轻了异沙夫糖苷的代谢重编程和抗炎作用。此外，异沙夫糖苷减弱脂多糖诱导的 ERK1/2 和 mTOR 磷酸化。这些结果表明异沙夫糖苷可以抑制脂多糖激活的小胶质细胞的炎症反应，其机制部分是由于抑制了 HIF-1 α介导的代谢重编程途径。