Choi Kyungsun, Kim Myungsun, Ryu Jeonghee, Choi Chulhee
Laboratory of Computational Cell Biology, Department of Brain and Bioengineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Neurosci Lett. 2007 Jun 21;421(1):37-41. doi: 10.1016/j.neulet.2007.05.017. Epub 2007 May 22.
Ginsenosides, the main component of Panax ginseng, have been known for the anti-inflammatory and anti-proliferative activities. In this study, we investigated the molecular mechanisms responsible for the anti-inflammatory effects of ginsenosides on activated astroglial cells. Among 13 different ginsenosides, intestinal bacterial metabolites Rh(2) and compound K (C-K) showed a significant inhibitory effect on tumor necrosis factor-alpha (TNF-alpha)-induced expression of intercellular adhesion molecule-1 in human astroglial cells. Pretreatment with C-K or Rh(2) suppressed TNF-alpha-induced phosphorylation of IkappaBalpha kinase and the subsequent phosphorylation and degradation of IkappaBalpha. Additionally, the same treatment inhibited TNF-alpha-induced phosphorylation of MKK4 and the subsequent activation of the JNK-AP-1 pathway. The inhibitory effect of ginsenosides on TNF-alpha-induced activation of the NF-kappaB and JNK pathways was not observed in human monocytic U937 cells. These results collectively indicate that ginsenoside metabolites C-K and Rh(2) exert anti-inflammatory effects by the inhibition of both NF-kappaB and JNK pathways in a cell-specific manner.
人参皂苷是人参的主要成分，其抗炎和抗增殖活性已为人所知。在本研究中，我们调查了人参皂苷对活化星形胶质细胞抗炎作用的分子机制。在13种不同的人参皂苷中，肠道细菌代谢产物Rh(2)和化合物K（C-K）对肿瘤坏死因子-α（TNF-α）诱导的人星形胶质细胞细胞间黏附分子-1表达具有显著抑制作用。用C-K或Rh(2)预处理可抑制TNF-α诱导的IκBα激酶磷酸化以及随后IκBα的磷酸化和降解。此外，相同处理可抑制TNF-α诱导的MKK4磷酸化以及随后JNK-AP-1途径的激活。在人单核细胞U937细胞中未观察到人参皂苷对TNF-α诱导的NF-κB和JNK途径激活的抑制作用。这些结果共同表明，人参皂苷代谢产物C-K和Rh(2)通过以细胞特异性方式抑制NF-κB和JNK途径发挥抗炎作用。
