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尾 and macrophage chemo-attractant protein (MCP)-1 in serum. In addition, CPA inhibited inducible nitric oxide synthase (iNOS), activation of nuclear factor (NF)-魏B by degradation and phosphorylation of I魏B伪, 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.