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Ethanol Extract of Potentilla supina Linne Suppresses LPS‐induced Inflammatory Responses through NF‐κB and AP‐1 Inactivation in Macrophages and in Endotoxic mice
Author(s) -
Lee HaeJun,
Shin JiSun,
Lee KyoungGoo,
Park Sang Cheol,
Jang Young Pyo,
Nam JungHwan,
Lee KyungTae
Publication year - 2017
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5773
Subject(s) - nitric oxide synthase , proinflammatory cytokine , nf κb , lipopolysaccharide , chemistry , activator (genetics) , nitric oxide , kinase , p38 mitogen activated protein kinases , protein kinase a , iκbα , iκb kinase , phosphorylation , microbiology and biotechnology , tumor necrosis factor alpha , pharmacology , biochemistry , biology , signal transduction , inflammation , immunology , organic chemistry , gene
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 E 2 , TNF‐α, interleukin‐6 and interleukin‐1β 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‐κB (NF‐κB), and this was associated with a decrease of translocation and phosphorylation of p65 NF‐κB by inhibiting the inhibitory κB‐α degradation and IKK‐α/β 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‐κB and activator protein‐1 activation and support its possible therapeutic role for the treatment of endotoxemia. Copyright © 2017 John Wiley & Sons, Ltd.