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Essential role of transient receptor potential vanilloid type 1 in evodiamine‐mediated protection against atherosclerosis

2012; Wiley; Volume: 207; Issue: 2 Linguagem: Inglês

10.1111/apha.12005

1748-1716

Jeng Wei, L.‐C. Ching, J.‐F. Zhao, Song‐Kun Shyue, Hsiang‐Ping Lee, Yu Ru Kou, Tzong‐Shyuan Lee,

Ziziphus Jujuba Studies and Applications

Abstract Aim We investigated whether transient receptor potential vanilloid type 1 ( TRPV 1) was involved in the therapeutic effect of evodiamine, a main bioactive component in the fruit of E vodiae rutaecarpa , on the development of atherosclerosis in apolipoprotein E ‐deficient ( A po E −/− ) mice and A po E −/− TRPV 1 −/− mice. Methods Histopathology was examined by haematoxylin and eosin staining, levels of cytokines and mediators were evaluated by ELISA kits, and protein expression was determined by W estern blotting. Results Chronic administration with evodiamine (10 mg kg −1 body weight) reduced the size of atherosclerotic lesions and alleviated the hyperlipidaemia and systemic inflammation, as well as hepatic macrovesicular steatosis, in A po E −/− mice. Treating A po E −/− mice with evodiamine enhanced hepatic cholesterol clearance, as revealed by upregulation of hepatic low‐density lipoprotein receptor and ATP ‐binding cassette ( ABC ) transporters ABCG 5, ABCG 8 and cholesterol 7α‐hydrolase. Genetic deletion of TRPV 1 in A po E −/− mice promoted the progression of atherosclerosis; elevated the serum levels of cholesterol, cytokines and chemokines; and exacerbated hepatic macrovesicular steatosis. Moreover, genetic deletion of TRPV 1 abrogated the evodiamine‐evoked atheroprotection but not anti‐obesity effect in A po E −/− mice. Conclusion Evodiamine may confer novel TRPV 1‐dependent atheroprotection and TRPV 1‐independent anti‐obesity action.