Mediation of antiinflammatory effects of Rg3-enriched red ginseng extract from Korean Red Ginseng via retinoid X receptor α–peroxisome-proliferating receptor γ nuclear receptors

Background: Ginseng has a wide range of beneficial effects on health, such as the mitigation of minor and major inflammatory diseases, cancer, and cardiovascular diseases. There are abundant data regarding the health-enhancing properties of whole ginseng extracts and single ginsenosides; however, no study to date has determined the receptors that mediate the effects of ginseng extracts. In this study, for the first time, we explored whether the antiinflammatory effects of Rg3-enriched red ginseng extract (Rg3-RGE) are mediated by retinoid X receptor α–peroxisome-proliferating receptor γ (RXRα-PPARγ) heterodimer nuclear receptors. Methods: Nitric oxide assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, quantitative reverse transcription polymerase chain reaction, nuclear hormone receptor–binding assay, and molecular docking analyses were used for this study. Results: Rg3-RGE exerted antiinflammatory effects via nuclear receptor heterodimers between RXRα and PPARγ agonists and antagonists. Conclusion: These findings indicate that Rg3-RGE can be considered a potent antiinflammatory agent, and these effects are likely mediated by the nuclear receptor RXRα-PPARγ heterodimer.