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

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 E-2 (PGE(2)), 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 PGE(2) 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)-kappa B; the phosphorylation of upstream kinases that activate NF-kappa B; 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-kappa B. Considering the in vitro and in vivo efficacy of El-ME, Evodia lepta could be developed into an anti-inflammatory herbal remedy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.