Methanol extract of Evodia lepta displays Syk/Src-targeted anti-inflammatory activity

Abstract

Ethnopharmacological relevance: Evodia lepta (Spreng.) Merr., in the Rutaceae family, is a medicinal plant traditionally used to treat inflammatory symptoms such as in meningitis and hepatitis. However, no study has systematically investigated its anti-inflammatory activities including its molecular mechanism.

Materials and methods: The effects of a methanol extract from the roots Evodia lepta (El-ME) were evaluated using lipopolysaccharide (LPS)-treated RAW264.7 cells producing nitric oxide (NO) and prostaglandin E2 (PGE2), and an HCl/ethanol-induced mouse gastritis model. Target molecules were identified by analyzing the activation of transcription factors and their upstream kinases.

Results: El-ME reduced the production of NO and PGE2 from LPS-activated RAW264.7 cells in a dose-dependent manner. El-ME also ameliorated the gastritis symptoms of EtOH/HCl-treated mice. The extract suppressed production of mRNA for the inducible NO synthase (iNOS) and cyclooxygenase (COX)-2; the nuclear translocation of nuclear factor (NF)-κB; the phosphorylation of upstream kinases that activate NF-κB; and the kinase activities of Syk and Src.

Conclusion: The anti-inflammatory effects of El-ME might be due to its suppression of Syk/Src and NF-κB. Considering the in vitro and in vivo efficacy of El-ME, Evodia lepta could be developed into an anti-inflammatory herbal remedy.

Keywords: (TNF)-α; 3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Anti-inflammatory; CMC; COX; EIA; ELISA; Evodia lepta (Spreng.) Merr.; IκB kinase; IκBκ; Iκκ; LPS; MTT; NF-κB; NO; PG; PI3K; RT-PCR; Rutaceae; Src; Syk; TLR; Toll-like receptors (TLR); cyclooxygenase; enzyme immunoassay; enzyme-linked immunosorbent assay; iNOS; inducible NO synthase; inhibitor of kappa B alpha; lipopolysaccharide; nitric oxide; nuclear factor-κB; phosphoinositide 3-kinase; prostaglandin; reverse transcriptase-polymerase chain reaction; sodium carboxymethylcellulose; spleen tyrosine kinase; tumor necrosis factor.