Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia.
Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia.
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发表时间：
2007
影响因子：
5.6
通讯作者：
Chunfu Wu;X. Bi;Jing Y Yang;J. Zhan;Y. Dong;J. Wang;Ji Ming Wang;Ruiwen Zhang;Xian Li
中科院分区：
文献类型：
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作者：
Chunfu Wu;X. Bi;Jing Y Yang;J. Zhan;Y. Dong;J. Wang;Ji Ming Wang;Ruiwen Zhang;Xian Li
人参皂苷是人参的主要活性成分，对中枢神经系统有保护作用。本文研究了人参皂苷- rd和-Rb2两种原人参二醇以及人参皂苷- rg1和-Re两种原人参二醇对脂多糖（LPS）激活的N9小胶质细胞产生一氧化氮（NO）和tnf - α (tnf - α)的影响。所有人参皂苷都能有效抑制lps激活的N9细胞中tnf - α的产生。人参皂苷- rg1和-Re抑制lps激活的N9细胞NO的产生，而人参皂苷- rb2和-Rd对NO的产生无抑制作用。人参皂苷抑制c-Jun nh2末端激酶（JNK）、c-Jun和细胞外信号调节激酶（ERK）的磷酸化，本研究结果表明，抑制lps诱导的ERK1/2和JNK活化可能是人参皂苷抑制RAW264.7的主要机制之一。为了阐明其抑制tnf - α和NO诱导的机制基础，我们还研究了人参皂苷对转录因子NF-kappaB蛋白水平的影响。这些活性与抑制剂kappaB （IkappaB）的下调有关。这些发现提示人参皂苷抑制lps诱导的小胶质细胞NO形成和tnf - α的产生可能是由于人参皂苷抑制NF-kappaB，这可能是人参皂苷抗炎作用的机制基础。人参皂苷对小胶质细胞的促炎反应有显著的抑制作用，提示其在伴随小胶质细胞活化的神经退行性疾病中的治疗潜力。
Ginsenosides, the main active components of ginseng, have been reported to exert neuroprotective effects in the central nervous system. In this report, the effects of ginsenoside-Rd and -Rb2, two protopanaxadiols, and ginsenoside-Rg1 and -Re, two protopanaxatriols, on the production of nitric oxide (NO) and TNF-alpha (TNF-alpha) by lipopolysaccharide (LPS)-activated N9 microglial cells were studied. All ginsenosides studied potently suppressed TNF-alpha production in LPS-activated N9 cells. Ginsenoside-Rg1 and -Re, but not ginsenoside-Rb2 and -Rd, inhibited the production of NO in LPS-activated N9 cells. Ginsenosides inhibited the phosphorylation of c-Jun NH2-terminal kinase (JNK), c-Jun and extracellular signal-regulated kinase (ERK), The findings herein show that the inhibition of LPS-induced ERK1/2 and JNK activation may be a contributing factor to the main mechanisms by which ginsenosides inhibits RAW264.7. To clarify the mechanistic basis for its ability to inhibit TNF-alpha and NO induction, the effect of ginsenosides on transcription factor NF-kappaB protein level was also examined. These activities were associated with the down-regulation of inhibitor kappaB (IkappaB). These findings suggest that the inhibition of LPS-induced NO formation and TNF-alpha production in microglia by ginsenosides is due to its inhibition of NF-kappaB, which may be the mechanistic basis for the anti-inflammatory effects of ginsenosides. The significant suppressive effects of ginsenosides on proinflammatory responses of microglia implicate their therapeutic potential in neurodegenerative diseases accompanied by microglial activation.