In the present study, we investigated the signaling pathways involved in the inhibition of cyclooxygenase 2 (COX-2) and iNOS by moscatilin under LPS challenge in murine macrophage-derived cell line RAW264.7. The results showed that moscatilin (10-100 μM) had a significant inhibition in a concentration-dependent manner on proinflammatory enzymes (COX-2 and iNOS) expression and macrophage activation under LPS (100 ng/mL) treatment. Hypoxia-inducible factor 1 (HIF-1)α was reported to initiate inflammation under cytokine stimulation or hypoxic conditions. In addition, the increase in transcriptional activity and translation process of HIF-1α under LPS stimulation resulted in HIF-1α accumulation. Moscatilin, a purified compound from Chinese herbs, had a dominant repression on HIF-1α expression via down-regulating HIF-1α mRNA without inhibition of cell viability, translation machinery, or proteasome-mediated degradation of HIF-1α. Moreover, the results showed that moscatilin suppressed nuclear translocation of nuclear factor (NF)-κB subunits, p65 and p50, and NF-κB activity by inhibiting phosphorylation of inhibitor of κBα. Taken together, we demonstrated that moscatilin inhibited both COX-2 and iNOS expressions after LPS treatment in RAW264.7. Furthermore, the inhibition of moscatilin seemed to be dependent on the repression of HIF-1α accumulation and NF-κB activation.
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine
- Emergency Medicine