Ginsenosides compound K and Rh2 inhibit tumor necrosis factor-α-induced activation of the NF-κB and JNK pathways in human astroglial cells

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 Rh2 and compound K (C-K) showed a significant inhibitory effect on tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 in human astroglial cells. Pretreatment with C-K or Rh2 suppressed TNF-α-induced phosphorylation of IκBα kinase and the subsequent phosphorylation and degradation of IκBα. Additionally, the same treatment inhibited TNF-α-induced phosphorylation of MKK4 and the subsequent activation of the JNK-AP-1 pathway. The inhibitory effect of ginsenosides on TNF-α-induced activation of the NF-κB and JNK pathways was not observed in human monocytic U937 cells. These results collectively indicate that ginsenoside metabolites C-K and Rh2 exert anti-inflammatory effects by the inhibition of both NF-κB and JNK pathways in a cell-specific manner.