Ginsenosides Rg3 and Rh2 inhibit the activation of AP-1 and protein kinase A pathway in lipopolysaccharide/interferon-γ-stimulated BV-2 microqlial cells
Ginsenosides Rg3 and Rh2 inhibit the activation of AP-1 and protein kinase A pathway in lipopolysaccharide/interferon-γ-stimulated BV-2 microqlial cells
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DOI：
10.1055/s-2006-931563
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发表时间：
2006-06-01
期刊：
影响因子：
2.7
通讯作者：
Kim, Dong-Hyun
中科院分区：
文献类型：
--
作者：
Bae, Eun-Ah;Kim, Eun-Jin;Kim, Dong-Hyun
采用脂多糖和干扰素-γ诱导的小鼠BV-2小胶质细胞模型，观察人参皂苷Rg3和Rh2改善大脑中动脉闭塞所致的缺血性脑损伤的抗炎作用。人参皂苷Rh2抑制NO的产生，其IC50值为17mM。Rh2对NO的抑制作用与其下调诱导型一氧化氮合酶(INOS)基因的蛋白和mRNA表达有关。人参皂苷Rh2抑制脂多糖/干扰素-γ诱导的BV-2细胞COX-2、促炎性肿瘤坏死因子-α和IL-1β的表达，增强抗炎细胞因子IL-10的表达。凝胶迁移率改变分析显示，人参皂苷Rh2显著抑制了脂多糖/干扰素-γ诱导的AP-1DNA结合活性，而增强了蛋白质与Cre序列的结合。但不影响核因子-kappaB的结合活性。因此，Rh2的抗炎作用似乎依赖于AP-1和蛋白激酶A(PKA)途径。人参皂苷Rg3对内毒素/干扰素-γ激活的BV-2细胞的抗炎作用弱于人参皂苷Rh2。提示人参皂苷Rg3的体内抗缺血作用可能来源于肠道菌群对人参皂苷Rg3的主要代谢产物人参皂苷Rh2，人参皂苷Rh2的抗脑小胶质细胞炎症作用可能与人参皂苷Rg3的抗炎作用有关。
The anti-inflammatory effect of ginsenosides Rg3 and Rh2, which improves ischemic brain injury induced by middle cerebral artery occlusion, was investigated in lipopolysaccharide (LPS) and IFN-gamma-induced murine BV-2 microglial cells. Ginsenoside Rh2 inhibited the production of NO, with an IC50 value of 17 mu M. The inhibitory effect of Rh2 on NO correlates with the decreased protein and mRNA expression of an inducible NO synthase (iNOS) gene. Additionally, ginsenoside Rh2 inhibited the expression of COX-2, pro-inflammatory TNF-alpha and IL-1 beta in BV-2 cells induced by LPS/IFN-gamma, while it increased the expression of the anti-inflammatory cytokine IL-10. Electrophorectic mobility shift assays revealed that ginsenoside Rh2 significantly inhibited the LPS/IFN-gamma-induced AP-1 DNA binding activity, while it enhanced the protein binding to CRE sequences. However, it did not affect NF-kappa B binding activity. Thus, the anti-inflammatory effect of Rh2 appears to depend on the AP-1 and protein kinase A (PKA) pathway. The anti-inflammatory effect of ginsenoside Rg3 against LPS/IFN-gamma-activated BV-2 cells was less potent than that of ginsenoside Rh2. These findings suggest that the in vivo anti-ischemic effect of ginsenoside Rg3 may originate from ginsenoside Rh2, which is a main metabolite of ginsenoside Rg3 by intestinal microflora, and that of ginsenoside Rh2 may be due to its anti-inflammatory effect in brain microglia.