Effect of Staphylea bumalda Leaf Extracts on Macrophage Activation through Toll-Like Receptor 2 and Toll-Like Receptor 4-dependent c-Jun N-terminal Kinase Activation

Background: The leaves of Staphylea bumalda (S. bumalda), a deciduous tree distributed in Korea, China, and Japan, are used to treat respiratory diseases or inflammation. However, the immune-enhancing activity of S. bumalda leaves has yet to be examined. Thus, we investigated the effect of water extracts of S. bumalda leaves (SBL) on macrophage activity using RAW264.7 mouse macrophage cells.
Methods and Results: SBL increased the production of immunomodulators such as NO, iNOS, IL-1β, IL-6, TNF-α, and MCP-1 and activated the phagocytic activity of RAW264.7 cells. SBL-mediated production of immunomodulators in RAW264.7 cells was blocked by inhibition of TLR2 and TLR4 and was attenuated by JNK inhibition. Moreover, SBL increased JNK phosphorylation, while inhibition of TLR2 and TLR4 blocked SBL-mediated JNK phosphorylation. These results suggest that SBL activates JNK through stimulating TLR2 and TLR4 in macrophages to induce immunomodulator production. In lipopolysaccharide-stimulated RAW264.7 cells, SBL inhibited the overproduction of immunomodulators.
Conclusions: Given these results, SBL showed immunostimulatory activity under normal conditions and immunosuppressive activity during LPS-induced excessive immune response.