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
{"title":"反式肉桂醛通过蛋白激酶B/v-Akt小鼠胸腺瘤病毒癌基因-内皮一氧化氮合酶途径促进一氧化氮释放,缓解SHR高血压。Cg-Leprcp/NDmcr大鼠","authors":"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","doi":"10.1016/S0254-6272(18)30886-0","DOIUrl":null,"url":null,"abstract":"<div><h3>OBJECTIVE</h3><p>To evaluate whether endothelial dysfunction and hypertension are prevented by trans-cinnamaldehyde (tCA) through the activation of endothelial nitric oxide synthase (eNOS).</p></div><div><h3>METHODS</h3><p>Human umbilical vein endothelial cells (HUVECs) were cultured <em>in vitro</em> and stimulated with tCA to determine cell viability using the methyl thiazolyl tetrazolium assay. The effect of tCA on nitric oxide (NO) production was determined by diaminofluorescein-dyes in the absence or presence of inhibitors of eNOS, AMPK, PKA, and AKT. The effect of tCA on blood pressure was determined by the tail-cuff method in obesity spontaneous hypertension (SHR. Cg-Leprcp/NDmcr) rats. The phosphorylation of eNOS and protein expression of the insulin-signaling pathway (InsR-IRS1-PI3K-AKT) were measured by western blot.</p></div><div><h3>RESULTS</h3><p>tCA at concentrations less than 100 did not affect cell viability in cultured HUVECs. Stimulation with tCA promoted NO release in a time-dependent manner compared with the control group. tCA-treated HUVECs also significantly increased AKT-Ser473 and eNOS- Ser1177 phosphorylation. In SHR-CP rats, treatment with tCA 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 eNOS, and increased urinary nitric oxidation.</p></div><div><h3>CONCLUSION</h3><p>tCA attenuated endothelial dysfunction and reduced blood pressure in SHR-CP rats. The underlying mechanisms may involve the increase in AKT and eNOS phosphorylation and the release of eNOS-derived NO.</p></div>","PeriodicalId":17513,"journal":{"name":"Journal of Traditional Chinese Medicine","volume":"38 4","pages":"Pages 548-555"},"PeriodicalIF":2.0000,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0254-6272(18)30886-0","citationCount":"3","resultStr":"{\"title\":\"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-Leprcp/NDmcr rats\",\"authors\":\"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\",\"doi\":\"10.1016/S0254-6272(18)30886-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>OBJECTIVE</h3><p>To evaluate whether endothelial dysfunction and hypertension are prevented by trans-cinnamaldehyde (tCA) through the activation of endothelial nitric oxide synthase (eNOS).</p></div><div><h3>METHODS</h3><p>Human umbilical vein endothelial cells (HUVECs) were cultured <em>in vitro</em> and stimulated with tCA to determine cell viability using the methyl thiazolyl tetrazolium assay. The effect of tCA on nitric oxide (NO) production was determined by diaminofluorescein-dyes in the absence or presence of inhibitors of eNOS, AMPK, PKA, and AKT. The effect of tCA on blood pressure was determined by the tail-cuff method in obesity spontaneous hypertension (SHR. Cg-Leprcp/NDmcr) rats. The phosphorylation of eNOS and protein expression of the insulin-signaling pathway (InsR-IRS1-PI3K-AKT) were measured by western blot.</p></div><div><h3>RESULTS</h3><p>tCA at concentrations less than 100 did not affect cell viability in cultured HUVECs. Stimulation with tCA promoted NO release in a time-dependent manner compared with the control group. tCA-treated HUVECs also significantly increased AKT-Ser473 and eNOS- Ser1177 phosphorylation. In SHR-CP rats, treatment with tCA 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 eNOS, and increased urinary nitric oxidation.</p></div><div><h3>CONCLUSION</h3><p>tCA attenuated endothelial dysfunction and reduced blood pressure in SHR-CP rats. The underlying mechanisms may involve the increase in AKT and eNOS phosphorylation and the release of eNOS-derived NO.</p></div>\",\"PeriodicalId\":17513,\"journal\":{\"name\":\"Journal of Traditional Chinese Medicine\",\"volume\":\"38 4\",\"pages\":\"Pages 548-555\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2018-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/S0254-6272(18)30886-0\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Traditional Chinese Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0254627218308860\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"INTEGRATIVE & COMPLEMENTARY MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Traditional Chinese Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0254627218308860","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
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-Leprcp/NDmcr rats
OBJECTIVE
To evaluate whether endothelial dysfunction and hypertension are prevented by trans-cinnamaldehyde (tCA) through the activation of endothelial nitric oxide synthase (eNOS).
METHODS
Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and stimulated with tCA to determine cell viability using the methyl thiazolyl tetrazolium assay. The effect of tCA on nitric oxide (NO) production was determined by diaminofluorescein-dyes in the absence or presence of inhibitors of eNOS, AMPK, PKA, and AKT. The effect of tCA on blood pressure was determined by the tail-cuff method in obesity spontaneous hypertension (SHR. Cg-Leprcp/NDmcr) rats. The phosphorylation of eNOS and protein expression of the insulin-signaling pathway (InsR-IRS1-PI3K-AKT) were measured by western blot.
RESULTS
tCA at concentrations less than 100 did not affect cell viability in cultured HUVECs. Stimulation with tCA promoted NO release in a time-dependent manner compared with the control group. tCA-treated HUVECs also significantly increased AKT-Ser473 and eNOS- Ser1177 phosphorylation. In SHR-CP rats, treatment with tCA 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 eNOS, and increased urinary nitric oxidation.
CONCLUSION
tCA attenuated endothelial dysfunction and reduced blood pressure in SHR-CP rats. The underlying mechanisms may involve the increase in AKT and eNOS phosphorylation and the release of eNOS-derived NO.
期刊介绍:
Journal of Traditional Chinese Medicine(JTCM) is devoted to clinical and theortical research on the use of acupuncture and Oriental medicine. The main columns include Clinical Observations, Basic Investigations, Reviews, Questions and Answers, an Expert''s Forum, and Discussions of Clinical Cases. Its key topics include acupuncture and electro-acupuncture, herbal medicine, homeopathy, masseotherapy, mind-body therapies, palliative care, and other CAM therapies.