The anti-inflammatory potential of Cortex Phellodendron in vivo and in vitro: Down-regulation of NO and iNOS through suppression of NF-κB and MAPK activation

Cortex Phellodendri amurensis (CPA), derived from the dried bark of Phellodendron amurense Rupr., is a traditional medicine widely used to treat various inflammation-related diseases. The aim of this study was to investigate the anti-inflammatory activity and molecular mechanism of CPA in vivo and in vitro. Mice were pretreated with CPA (200 mg/kg, p.o.) for three consecutive days; 2 h after the last CPA treatment, mice were intraperitoneally injected with lipopolysaccharide (LPS) to induce endotoxemia (35 mg/kg). After treatment, we assessed survival rate, protein levels and cytokine expression. In addition, we confirmed the molecular mechanism of anti-inflammatory effects of CPA in LPS-stimulated macrophage RAW 264.7 cells. The results showed that CPA significantly increased mice survival rates and down-regulated LPS-induced interleukin (IL)-6, IL-1 beta and macrophage chemo-attractant protein (MCP)-1 in serum. In addition, CPA inhibited inducible nitric oxide synthase (iNOS), activation of nuclear factor (NF)-kappa B by degradation and phosphorylation of I kappa B alpha, and attenuated phosphorylation of mitogen-activated protein kinases (MAPKs; ERIC 1/2, p38 and JNK) from mice challenged with LPS. Moreover, in RAW 264.7 cells, CPA dose-dependently down-regulated LPS-stimulated NO, iNOS expression, as well as inflammatory cytokines and protein expression, consistent with the results in vivo. The anti-inflammatory properties of CPA in vitro and in vivo suggest its utility for attenuating inflammation-related diseases. (C) 2014 Elsevier B.V. All rights reserved.