Methanol extract of Osbeckia stellata suppresses lipopolysaccharide- and HCl/ethanol-induced inflammatory responses by inhibiting Src/Syk and IRAK1

Abstract: Ethnopharmacological relevance: Osbeckia stellata Buch.-Ham. ex D.Don is traditionally prescribed to treat various inflammatory diseases. However, how this plant is able to modulate inflammatory responses is unknown. This study explored the anti-inflammatory effects of 99% methanol extracts of O. stellata (Os-ME). Materials and Methods: The anti-inflammatory effect of Os-ME was evaluated by measuring the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells and by determining gastric inflammatory lesions in mice induced by HCl/ethanol (EtOH). The molecular mechanisms of the inhibitions were elucidated by analyzing the activation of transcription factors, upstream signaling cascade, and the kinase activities of target enzymes. Results: Os-ME dose-dependently diminished the release of NO and PGE2, and suppressed the expression of inducible NO synthase and cyclooxygenase-2 in LPS-treated RAW264.7 cells. Os-ME clearly inhibited the translocation of c-Rel, a subunit of nuclear factor κB (NF-κB), and c-Fos, a subunit of activator protein-1 (AP-1), and their regulatory upstream enzymes including Src, Syk, and IRAK1. Interestingly, orally administered Os-ME ameliorated acute inflammatory symptoms and suppressed the activation of Src, Syk, and IKAK1 induced by HCl/EtOH treatment in mouse stomach. Conclusion: Os-ME can be considered as an orally available anti-inflammatory herbal remedy with Src/Syk/NF-κB and IRAK1/AP-1 inhibitory properties. [Copyright &y& Elsevier]