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 (ApoE(-/-)) mice and ApoE(-/-)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 ApoE(-/-) mice. Treating ApoE(-/-) 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 ApoE(-/-) 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 ApoE(-/-) mice. CONCLUSION: Evodiamine may confer novel TRPV1-dependent atheroprotection and TRPV1-independent anti-obesity action.
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 (ApoE(-/-)) mice and ApoE(-/-)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 ApoE(-/-) mice. Treating ApoE(-/-) 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 ApoE(-/-) 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 ApoE(-/-) mice. CONCLUSION:Evodiamine may confer novel TRPV1-dependent atheroprotection and TRPV1-independent anti-obesity action.