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) ameliorates IL-6, IL-1β and MCP-1.•CPA inhibits LPS-induced NO production and iNOS protein.•CPA prevented NF-κB expression by the phosphorylation and degradation of IκBα.•CPA decreased signaling pathways of the MAP kinases.•CPA increased mice survival rates.

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-1β and macrophage chemo-attractant protein (MCP)-1 in serum. In addition, CPA inhibited inducible nitric oxide synthase (iNOS), activation of nuclear factor (NF)-κB by degradation and phosphorylation of IκBα, and attenuated phosphorylation of mitogen-activated protein kinases (MAPKs; ERK 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.

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