Trans-cinnamaldehyde promotes nitric oxide release via the protein kinase-B/v-Akt murine thymoma viral oncogene-endothelial nitric oxide synthase pathway to alleviate hypertension in SHR.Cg-Lepr^(cp)/NDmcr rats  

作　　者：Zhang Lu Wu Lili Liu Ximing Yoshitomi Hisae Ikeda Katsumi Negishi Hiroko Pan Yajing Sun Wen Qin Lingling Li Juan-E Xu Tunhai Liu Tonghua Gao Ming 

机构地区：[1]Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing 100029, China [2]Department of Endocrinology, Dongfang Hospital affiliated to Beijing University of Chinese Medicine, Beijing 100078, China [3]Chinese Medical Science Research Institute, Guang An Men Hospital, Beijing 100053, China [4]School of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo 663-8179, Japan [5]Science and Technology Department, Beijing University of Chinese Medicine, Beijing 100029, China [6]Third Affiliated Hospital of Xi'an Jiao Tong University, Xi'an 710068, China [7]School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100029, China

出　　处：《Journal of Traditional Chinese Medicine》2018年第4期548-555,共8页中医杂志（英文版）

基　　金：the International Joint Research Center of Prevention and Treatment of Diabetes with Traditional Chinese Medicine of Ministry of Science and Technology of China,Key Laboratory of Health Cultivation of the Ministry of Education,Key Laboratory of Health Cultivation of Beijing(No.BZ0259);Beijing International Scientific and Technological Cooperation Base for the Prevention and Treatment of Diabetes with Traditional Chinese Medicine.The Science Foundation of China(No.8150-3538);the International Scientific Collaborative Project(No.2010DFB33260)

摘　　要：OBJECTIVE:To evaluate whether endothelial dysfunction and hypertension are prevented by trans-cinnamaldehyde(t CA) through the activation of endothelial nitric oxide synthase(e NOS).METHODS:Human umbilical vein endothelial cells(HUVECs) were cultured in vitro and stimulated with t CA to determine cell viability using the methyl thiazolyl tetrazolium assay.The effect of t CA on nitric oxide(NO) production was determined by diaminofluorescein-dyes in the absence or presence of inhibitors of e NOS,AMPK,PKA,and AKT.The effect of t CA on blood pressure was determined by the tail-cuff method in obesity spontaneous hypertension(SHR.Cg-Leprcp/NDmcr) rats.The phosphorylation of e NOS and protein expression of the insulin-signaling pathway(Ins R-IRS1-PI3 K-AKT)were measured by western blot.RESULTS:t CA at concentrations less than 100 μM did not affect cell viability in cultured HUVECs.Stimulation with t CA promoted NO release in a time-dependent manner compared with the control group.t CA-treated HUVECs also significantly increased AKT-Ser473 and e NOS-Ser1177 phosphorylation.In SHR-CP rats,treatment with t CA at a dose of 40 mg/kg/day for 6 weeks markedly reduced the systolic blood pressure and diastolic blood pressure,increased the phosphorylation of AKT and e NOS,and increased urinary nitric oxidation.CONCLUSION:t CA attenuated endothelial dysfunction and reduced blood pressure in SHR-CP rats.The underlying mechanisms may involve the increase in AKT and e NOS phosphorylation and the release of e NOS-derived NO.OBJECTIVE：To evaluate whether endothelial dysfunction and hypertension are prevented by trans-cinnamaldehyde（t CA） through the activation of endothelial nitric oxide synthase（e NOS）.METHODS：Human umbilical vein endothelial cells（HUVECs） were cultured in vitro and stimulated with t CA to determine cell viability using the methyl thiazolyl tetrazolium assay.The effect of t CA on nitric oxide（NO） production was determined by diaminofluorescein-dyes in the absence or presence of inhibitors of e NOS,AMPK,PKA,and AKT.The effect of t CA on blood pressure was determined by the tail-cuff method in obesity spontaneous hypertension（SHR.Cg-Leprcp/NDmcr） rats.The phosphorylation of e NOS and protein expression of the insulin-signaling pathway（Ins R-IRS1-PI3 K-AKT）were measured by western blot.RESULTS：t CA at concentrations less than 100 μM did not affect cell viability in cultured HUVECs.Stimulation with t CA promoted NO release in a time-dependent manner compared with the control group.t CA-treated HUVECs also significantly increased AKT-Ser473 and e NOS-Ser1177 phosphorylation.In SHR-CP rats,treatment with t CA at a dose of 40 mg/kg/day for 6 weeks markedly reduced the systolic blood pressure and diastolic blood pressure,increased the phosphorylation of AKT and e NOS,and increased urinary nitric oxidation.CONCLUSION：t CA attenuated endothelial dysfunction and reduced blood pressure in SHR-CP rats.The underlying mechanisms may involve the increase in AKT and e NOS phosphorylation and the release of e NOS-derived NO.

关 键 词：trans-cinnamaldehyde nitric Oxide eNOS HYPERTENSION HUVEC 

分 类 号：R285.5[医药卫生—中药学]