Gypenoside IX Suppresses p38 MAPK/Akt/NFκB Signaling Pathway Activation and Inflammatory Responses in Astrocytes Stimulated by Proinflammatory Mediators
Gypenoside IX Suppresses p38 MAPK/Akt/NFκB Signaling Pathway Activation and Inflammatory Responses in Astrocytes Stimulated by Proinflammatory Mediators
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绞股蓝皂苷 IX 抑制促炎介质刺激的星形胶质细胞中 p38 MAPK/Akt/NF kappa B 信号通路激活和炎症反应
DOI：
10.1007/s10753-017-0654-x
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发表时间：
2017-12-01
期刊：
影响因子：
5.1
通讯作者：
Wang, Zhengtao
中科院分区：
文献类型：
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作者：
Wang, Xiaoshuang;Yang, Liu;Wang, Zhengtao
绞股蓝皂苷 IX (GP IX) 是从三七中分离出来的纯化合物。绞股蓝皂苷有助于多种神经系统疾病的恢复。通过抑制星形胶质细胞的活化，绞股蓝皂苷可以改善认知障碍。然而，迄今为止，关于 GP IX 是否可以抑制星形胶质细胞的炎症反应或反应性星形胶质细胞增生，人们知之甚少。在本研究中，在体外和体内促炎介质诱导的反应性星形胶质细胞中研究了 GP IX 的抗炎作用。 GP IX 在脂多糖刺激的神经胶质细胞系 C6 细胞中，在蛋白质或 mRNA 水平显着降低诱导型一氧化氮合酶 (iNOS)、环氧合酶-2 (COX-2)、肿瘤坏死因子-α (TNF-α)、白细胞介素 6 (IL-6) 和白细胞介素 1 β (IL-1 β) 的产生 (LPS)/TNF-α 组合。它还减轻了 LPS 处理小鼠大脑皮层中的星形胶质细胞增生并减少了炎症介质的产生。进一步的研究表明，GP IX 抑制核因子 kappa B (NF kappa B) 的核转位并降低其转录活性。同时，GP IX 在体外和体内炎症条件下均显着减弱 NF kappa B、kappa B 抑制剂 (I kappa B)、Akt 和 p38 丝裂原激活蛋白激酶 (MAPK) 的磷酸化。这些发现表明 GP IX 可能通过抑制 Akt/p38 MAPK/NF kappa B 信号通路来抑制反应性星形胶质细胞增生。 GP IX 可能是一种有前途的候选药物或前药，用于治疗以反应性星形胶质细胞增生为特征的神经炎症性疾病。
Gypenoside IX (GP IX) is a pure compound isolated from Panax notoginseng. Gypenosides have been implicated to benefit the recovery of enormous neurological disorders. By suppressing the activation of astrocytes, gypenosides can improve the cognitive impairment. However, so far, little is known about whether GP IX could restrain the inflammatory responses in astrocytes or reactive astrogliosis. In present study, the anti-inflammatory effects of GP IX were investigated in reactive astrocytes induced by proinflammatory mediators both in vitro and in vivo. GP IX significantly reduced the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) at either protein or mRNA level in glial cell line C6 cells stimulated by lipopolysaccharide (LPS)/TNF-alpha combination. It also alleviated the astrogliosis and decreased the production of inflammatory mediators in brain cortex of LPS-treated mice. Further study disclosed that GP IX inhibited nuclear translocation of nuclear factor kappa B (NF kappa B) and reduced its transcriptional activity. Meanwhile, GP IX significantly attenuated the phosphorylation of NF kappa B, inhibitor of kappa B (I kappa B), Akt, and p38 mitogen-activated protein kinase (MAPK) under inflammatory conditions both in vitro and in vivo. These findings indicated that GP IX might suppress reactive astrogliosis by suppressing Akt/p38 MAPK/NF kappa B signaling pathways. And GP IX might be a promising drug candidate or prodrug for the therapy of neuroinflammatory disorders characterized with reactive astrogliosis.