Immune-enhancing activity of Hydrangea macrophylla subsp. serrata leaves through TLR4/ROS-dependent activation of JNK and NF-κB in RAW264.7 cells and immunosuppressed mice

[Display omitted] •WE-HML increases cell viability and phagocytosis in RAW264.7 cells.•WE-HML increases the production of immune-enhancing mediators in RAW264.7 cells.•WE-HML induces ROS-dependent JNK and NF-κB signaling activation in RAW264.7 cells.•WE-HML increases TLR4 expression in RAW264.7 cells.•WE-HML increases immune-enhancement-related indicators in immunosuppressed mice.•WE-HML inhibits pro-inflammatory mediators in LPS-stimulated RAW264.7 cells. In this study, we investigated the immune-enhancing activity of water extracts from Hydrangea macrophylla subsp. serrata (WE-HML). WE-HML increased cell viability and production of immunomodulators, which contributed to activating phagocytic activity in RAW264.7 cells. Inhibition of JNK and NF-κB reduced the production of immunomodulators by WE-HML. ROS inhibition suppressed the production of immunomodulators, and the activation of JNK and NF-κB signaling by WE-HML. TLR4 inhibition attenuated the production of immunomodulators, and activation of JNK and NF-κB signaling by WE-HML. In the immunosuppressed mouse model, WE-HML increased the spleen index, the levels of the cytokines, the numbers of white blood cells, lymphocytes, and neutrophils. However, WE-HML inhibited LPS-mediated overproduction of pro-inflammatory mediators in RAW264.7 cells, which indicated that WE-HML may have anti-inflammatory activity under excessive inflammatory conditions. Taken together, WE-HML may be considered to have immune-enhancing activity and expected to be used as a potential immune-enhancing agent.