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Schizonepeta tenuifolia ethanol extract exerts anti-inflammatory activity through the inhibition of TLR4 signaling in lipopolysaccharide-stimulated macrophage cells.

Inflammatory diseases remain the leading cause of mortality worldwide in both men and women. Schizonepeta tenuifolia (ST) exerts a wide range of physiological activities and has been found to possess beneficial efficacies against inflammation-related diseases; however, the molecular mechanisms underlying this anti-inflammatory activity remain to be elucidated. We investigated the molecular basis for the downregulation of toll-like receptor 4 (TLR4) signal transduction by ST ethanol extract in lipopolysaccharide (LPS)-stimulated macrophages. In this study, ST ethanol extract (100 μg/mL) did not induce cell cytotoxicity and was used in all the following experiments. Treatment of LPS-stimulated macrophages with ST ethanol extract resulted in a significant decrease in cyclooxygenase-2 and prostaglandin E2 levels, and inducible nitric oxide synthase-mediated NO production. LPS-induced expression of cell surface molecules (CD80 and CD86) and production of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, and IL-6) were inhibited by ST ethanol extract. Further, we also found that the anti-inflammatory activities of ST ethanol extract was caused by inhibition of LPS-induced activation of mitogen-activated protein kinases, such as extracellular signal-regulated kinase 1/2 and p38, and the translocation of nuclear factor κB through TLR4 in macrophages. Thus, ST ethanol extract may possess novel and potent therapeutic efficacy for the treatment of inflammatory disease.