首页> 外文期刊>Journal of Functional Foods >Angiotensin I-converting enzyme (ACE) inhibition and nitric oxide (NO)-mediated antihypertensive effect of octaphlorethol A isolated from Ishige sinicola: In vitro molecular mechanism and in vivo SHR model
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Angiotensin I-converting enzyme (ACE) inhibition and nitric oxide (NO)-mediated antihypertensive effect of octaphlorethol A isolated from Ishige sinicola: In vitro molecular mechanism and in vivo SHR model

机译:分离自Ishige sinicola的八碳四烯醇A的血管紧张素I转换酶(ACE)抑制和一氧化氮(NO)介导的降压作用:体外分子机制和体内SHR模型

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Angiotensin l-converting enzyme (ACE) inhibition and nitric oxide (NO) production are important factors that regulate blood pressure. In this study, the effects of octaphlorethol A (OPA) isolated from Ishige sinicola on ACE inhibition and NO production, the molecular mechanism underlying ACE inhibition, as well as its antihypertensive effect in spontaneously hypertensive rats (SHRs) were investigated. IC50 value of OPA against ACE was 59 mu M. Molecular modelling studies indicated that the compound interacts with Cys370, Glu162, Glu376, Glu403, Glu411, Asp377, His383, His387, Tyr520, Arg522,Tyr523, and Lys511. In human endothelial cells, OPA increased endothelial nitric oxide synthase (eNOS) phosphorylation. We also demonstrated that these OPA-induced effects essentially depended on protein kinase B (Akt) and AMP-activated protein kinase (AMPK) activation. Furthermore, systolic blood pressure was reduced (21.9 mmHg in 6 h) by administration of the compound in SHRs. The results of this study suggested that OPA could be developed as a therapeutic agent for hypertension. (C) 2015 Elsevier Ltd. All rights reserved.
机译:血管紧张素I转换酶(ACE)的抑制和一氧化氮(NO)的产生是调节血压的重要因素。在这项研究中,研究了从Ishige sinicola分离得到的八氢大麻酚A(OPA)对ACE抑制和NO产生,ACE抑制的分子机制以及对自发性高血压大鼠(SHRs)的降压作用。 OPA对ACE的IC50值为59μM。分子模型研究表明该化合物与Cys370,Glu162,Glu376,Glu403,Glu411,Asp377,His383,His387,Tyr520,Arg522,Tyr523和Lys511相互作用。在人内皮细胞中,OPA可增加内皮一氧化氮合酶(eNOS)的磷酸化。我们还证明了这些OPA诱导的作用基本上取决于蛋白激酶B(Akt)和AMP激活的蛋白激酶(AMPK)激活。此外,通过在SHRs中施用该化合物可降低收缩压(6小时内为21.9 mmHg)。这项研究的结果表明,OPA可以开发为高血压的治疗剂。 (C)2015 Elsevier Ltd.保留所有权利。

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