Ginsenoside Rg3 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 E2 levels were performed in vitro and in a zymosan-induced peritonitis C57BL/6 mouse model. Results Ginsenoside Rg3 was identified as a proresolving ginseng compound based on the induction of M2 macrophage polarization. Ginsenoside Rg3 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 Rg3 was also observed in vivo in a zymosan-induced peritonitis model. Ginsenoside Rg3 accelerated the resolution process when administered at peak inflammatory response into the peritoneal cavity. Conclusion These results suggest that ginsenoside Rg3 induces the M2 polarization of macrophages and accelerates the resolution of inflammation. This finding opens a new avenue in ginseng pharmacology.