In vitro macrophage activation by Sageretia thea fruits through TLR2/TLR4-dependent activation of MAPK, NF-κB and PI3K/AKT signalling in RAW264.7 cells

Sageretia thea fruits (STF) are known to have a higher content of functional ingredients and nutrients than blueberries, but studies related to its pharmacological activity are insufficient. Thus, in this study, we investigated whether STF exhibits immune-enhancing activity through macrophage activation. STF increased the production of immunomodulators, cell viability and phagocytosis in RAW264.7 cells. The inhibition of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) blocked STF-mediated production of immunomodulators in RAW264.7 cells. Inhibition of mitogen-activated protein kinases (MAPKs), nuclear factor-kappaB (NF-κB) and phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signalling pathway reduced STF-mediated production of immunomodulators and the activation of MAPK, NF-κB and PI3K/AKT signalling pathway by STF suppressed the inhibition of TLR2/TLR4. However, STF blocked the overproduction of immunomodulators in LPS-stimulated RAW264.7 cells. Taken together, STF induced macrophage activation through TLR2/TLR4-dependent activation of MAPK, NF-κB and PI3K/AKT signalling.