Ethanol Extract of Potentilla supina Linne Suppresses LPS-induced Inflammatory Responses through NF-κB and AP-1 Inactivation in Macrophages and in Endotoxic mice

In this study, we investigated the antiinflammatory effects of ethanol extracts of Potentilla. supina Linne (EPS) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and septic mice. EPS suppressed LPS-induced nitric oxide, prostaglandin E2, TNF-alpha, interleukin-6 and interleukin-1 beta at production and mRNA levels in LPS-induced RAW 264.7 macrophages. Consistent with these observations, EPS attenuated the expressions of inducible nitric oxide synthase and cyclooxygenase-2 by downregulation of their promoter activities. Molecularly, EPS reduced the LPS-induced transcriptional activity and DNA-binding activity of nuclear factor-kB (NF-kappa B), and this was associated with a decrease of translocation and phosphorylation of p65 NF-kappa B by inhibiting the inhibitory kappa B-alpha degradation and IKK-alpha/beta phosphorylation. Furthermore, EPS inhibited the LPS-induced activation of activator protein-1 by reducing the expression of c-Fos and c-Jun in nuclear. EPS also suppressed the phosphorylation of mitogen-activated protein kinase, such as p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. In an LPS-induced endotoxemia mouse model, pretreatment with EPS reduced the mRNA levels of inducible nitric oxide synthase, cyclooxygenase-2 and proinflammatory cytokines and increased the survival rate of mice. Collectively, these results suggest that the antiinflammatory effects of EPS were associated with the suppression of NF-kappa B and activator protein-1 activation and support its possible therapeutic role for the treatment of endotoxemia. Copyright (C) 2017 John Wiley & Sons, Ltd.