Antioxidative, anti-inflammatory, and matrix metalloproteinase inhibitory activities of 20(S)-ginsenoside Rg3 in cultured mammalian cell lines.

Ginsenoside Rg3 is one of ginsenosides that are the well-known bioactive principles of Panax ginseng. Among the two stereoisomeric forms of Rg3, 20(S)-ginsenoside Rg3 [20(S)-Rg3] is predominant. 20(S)-Rg3 is capable of suppressing the nitric oxide (NO), reactive oxygen species (ROS) and prostaglandin E2 (PGE2) productions induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells in a concentration-dependent manner. In the same stimulated macrophages, 20(S)-Rg3 was able to suppress matrix metalloproteinase-9 (MMP-9) activity and suppress cyclooxygenase-2 (COX-2) expression. It suppressed the production of some proinflammatory cytokines, such as TNF-α, IL-1ß and IL-6, and the cell mobility enhanced by LPS in the macrophage cells. 20(S)-Rg3 displayed suppressive effect on the ROS level but not on the NO level, and down-regulating effect on MMP-9 but not on MMP-2 in non-stimulated HaCat keratinocytes. 20(S)-Rg3 also exhibited suppressive effect on the MMP-9 gelatinolytic activity enhanced in the HaCat keratinocytes stimulated with tumor necrosis factor-α (TNF-α), one of the major proinflammatory cytokines. However, 20(S)-Rg3 was not able to modulate the NO level even in the presence of TNF-α. Taken together, anti-inflammatory and related antioxidative and MMP-9 inhibitory activities of 20(S)-Rg3, the major stereoisomeric form of ginsenoside Rg3, are confirmed in macrophage and keratinocyte cell lines.