Syk/Src-targeted anti-inflammatory activity of Codariocalyx motorius ethanolic extract

Ethnopharmacological relevance: Codariocalyx motorius (Houtt.) H. Ohashi (Fabaceae) is one of several ethnopharmacologically valuable South Asian species prescribed as an herbal medicine for various inflammatory diseases. Due to the lack of systematic studies on this plant, we aimed to explore the inhibitory activity of Codariocalyx motorius toward inflammatory responses using its ethanolic extract (Cm-EE). Materials and methods: Lipopolysaccharide (LPS)-treated macrophages and a HCl/EtOH-induced gastritis model were used for evaluation of the anti-inflammatory activity of Cm-EE. HPLC and spectroscopic analysis were employed to identify potential active components. Mechanistic approaches to determine target enzymes included kinase assays, reporter gene assays, and overexpression of target enzymes. Results: Cm-EE strongly suppressed nitric oxide (NO) and prostaglandin E-2 (PGE(2)) release. Cm-EE-mediated inhibition was observed at the transcriptional level in the form of suppression of NF-kappa B (p65) translocation and activation. This extract also lowered the levels of phosphorylation of Src and Syk, their kinase activity, and their formation of signalling complexes by binding to the downstream enzyme p85/PI3K. In accord with these findings, the phosphorylation of p85 induced by overexpression of Src or Syk was also diminished by Cm-EE. Orally administered Cm-EE clearly inhibited gastritic ulcer formation and the phosphorylation of I kappa B alpha and Src in HCl/EtOH-treated stomachs of mice. By phytochemical analysis, luteolin and its glycoside, apigenin-7-O-glucuronide, and scutellarein-6-O-glucuronide were identified as major components of Cm-EE. Among these, it was found that luteolin was able to strongly suppress NO and PGE(2) production under the same conditions. Conclusion: Syk/Src-targeted inhibition of NF-kappa B by Cm-EE could be a major anti-inflammatory mechanism contributing to its ethno pharmacological role as an anti-inflammatory herbal medicine. (C) 2014 Elsevier Ireland Ltd. All rights reserved.