Heracleum moellendorffii root extracts exert immunostimulatory activity through TLR2/4‐dependent MAPK activation in mouse macrophages, RAW264.7 cells

Heracleum moellendorffii (H. moellendorffii) is a family of Umbelliferae and has long been used for food and medicinal purposes. However, the immune‐enhancing activity of H. moellendorffii has not been studied. Thus, we evaluated in vitro immune‐enhancing activity of H. moellendorffii through macrophage activation using RAW264.7 cells. Heracleum moellendorffii Root extracts (HMR) increased the production of immunomodulators such as NO, iNOS, IL‐1β, IL‐6 IL‐12, TNF‐α, and MCP‐1 and activated phagocytosis in RAW264.7 cells. Inhibition of TLR2 and TLR4 reduced the production of immunomodulators induced by HMR. Inhibition of MAPK signaling attenuated the production of immunomodulators induced by HMR, but inhibitions of NF‐κB or PI3K/AKT signaling did not affect HMR‐mediated production of immunomodulators. HMR activated MAPK signaling pathway, and activation of MAPK signaling pathways by HMR was reversed by TLR2 and TLR4 inhibition. Based on the results of this study, HMR is thought to activate macrophages through the production of immunomodulators and phagocytosis activation through TLR2/4‐dependent MAPK signaling pathway. Therefore, it is thought that HMR has the potential to be used as an agent for enhancing immunity.