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- Title
Essential role of transient receptor potential vanilloid type 1 in evodiamine-mediated protection against atherosclerosis.
- Authors
Wei, J.; Ching, L.‐C.; Zhao, J.‐F.; Shyue, S.‐K.; Lee, H.‐F.; Kou, Y. R.; Lee, T.‐S.
- Abstract
Aim We investigated whether transient receptor potential vanilloid type 1 ( TRPV1) was involved in the therapeutic effect of evodiamine, a main bioactive component in the fruit of Evodiae rutaecarpa, on the development of atherosclerosis in apolipoprotein E-deficient ( Apo E−/−) mice and Apo E−/− TRPV1−/− 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 Western 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 Apo E−/− mice. Treating Apo E−/− mice with evodiamine enhanced hepatic cholesterol clearance, as revealed by upregulation of hepatic low-density lipoprotein receptor and ATP-binding cassette ( ABC) transporters ABCG5, ABCG8 and cholesterol 7α-hydrolase. Genetic deletion of TRPV1 in Apo 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 TRPV1 abrogated the evodiamine-evoked atheroprotection but not anti-obesity effect in Apo E−/− mice. Conclusion Evodiamine may confer novel TRPV1-dependent atheroprotection and TRPV1-independent anti-obesity action.
- Subjects
TRP channels; ATHEROSCLEROSIS; INFLAMMATION; ANTIOBESITY agents; HYPERLIPIDEMIA; APOLIPOPROTEIN E; GENE expression
- Publication
Acta Physiologica, 2013, Vol 207, Issue 2, p299
- ISSN
1748-1708
- Publication type
Article
- DOI
10.1111/apha.12005