Ginsenoside Rg(3) promotes inflammation resolution through M2 macrophage polarization

BACKGROUND: Ginsenosides have been reported to have many health benefits, including anti-inflammatory effects, and the resolution of inflammation is now considered to be an active process driven by M2-type macrophages. In order to determine whether ginsenosides modulate macrophage phenotypes to reduce inflammation, 11 ginsenosides were studied with respect to macrophage polarization and the resolution of inflammation. METHODS: Mouse peritoneal macrophages were polarized into M1 or M2 phenotypes. Reverse transcription-polymerase chain reaction, Western blotting, and measurement of nitric oxide (NO) and prostaglandin E(2) levels were performed in vitro and in a zymosan-induced peritonitis C57BL/6 mouse model. RESULTS: Ginsenoside Rg(3) was identified as a proresolving ginseng compound based on the induction of M2 macrophage polarization. Ginsenoside Rg(3) not only induced the expression of arginase-1 (a representative M2 marker gene), but also suppressed M1 marker genes, such as inducible NO synthase, and NO levels. The proresolving activity of ginsenoside Rg(3) was also observed in vivo in a zymosan-induced peritonitis model. Ginsenoside Rg(3) accelerated the resolution process when administered at peak inflammatory response into the peritoneal cavity. CONCLUSION: These results suggest that ginsenoside Rg(3) induces the M2 polarization of macrophages and accelerates the resolution of inflammation. This finding opens a new avenue in ginseng pharmacology.