ACE抑制肽构效关系研究进展

血管紧张素转化酶(angiotensin-converting enzyme,ACE)抑制肽是一类从食源性蛋白质中分离得到的具有降高血压活性的多肽。由于其降血压效果好,而且没有降压药物的毒副作用从而引起了广泛关注。近年来,ACE抑制肽的构效关系研究成为研究重点。结构生物信息学研究表明,ACE抑制肽的ACE抑制能力不仅与其分子质量有关,而且与其氨基酸序列以及其立体空间构象之间存在高度相关性。ACE抑制肽的抑制类型与ACE抑制活性、构效关系也存在一定相关性。对ACE抑制肽构效关系进行深入研究将有助于指导开发高活性的功能性食品及降血压药物。     

血管紧张素转换酶抑制肽定量构效关系研究进展

在血压调节方面,血管紧张素转换酶（ACE）的活性是重要的影响因子。ACE抑制肽具有抑制ACE活性、降低血压等作用。其毒副作用小、安全性高。该文主要对血压调节机制、ACE抑制肽的降压机理、食源性ACE抑制肽的制备以及定量构效关系进行综述介绍,对指导ACE抑制肽的分子设计过程给予理论分析,有望开发出高活性的功能性食品及降血压药物。     

海洋蛋白源ACE抑制肽研究进展

血管紧张素转化酶(ACE)抑制肽在血压调节中起着重要作用,食源性ACE抑制肽具有较强降血压效果,是调节血压的潜在活性成分。海洋蛋白源ACE抑制肽是食源性活性肽的重要组成部分,是未来研究的热点。本文综述了海洋蛋白源ACE抑制肽的制备、纯化、结构鉴定、体外和体内活性研究及构效关系等研究进展,同时对海洋蛋白源ACE抑制肽的研究和应用前景进行展望。     

食源性ACE抑制肽的研究进展

ACE抑制肽是具有降血压功效的生物活性肽,食源性ACE抑制肽具有天然可靠、无毒、安全等优点。文章综述了ACE抑制肽的降血压机理,食源性ACE抑制肽的来源、制备和分离纯化方法以及活性评价,发现食源ACE抑制肽具有重要的理论价值与应用价值,能够为调节血压的功能性食品的开发提供一定参考。     

泥鳅ACE抑制肽的体外活性研究

以泥鳅蛋白为原料,酶解制备具有降血压活性的短肽,研究该肽的稳定性。在加热温度≤80℃条件下加热2h,泥鳅降血压肽(<2.5ku)的ACE抑制活性没有显著变化。当2.0≤pH≤8.0时,泥鳅降血压肽的ACE抑制活性变化不显著。冷冻干燥优于喷雾干燥。Mg2+对泥鳅降压肽的降压活性起到促进作用,而Zn2+和Mn2+抑制了肽的降压活性。葡萄糖对降压肽活性的影响程度明显大于蔗糖,随着浓度的升高,其ACE抑制活性逐渐降低,褐变程度加深;氯化钠对降压活性的影响不明显。在模拟胃肠道消化体系中,胃蛋白酶的消化显著提高了产物的降压活性;胰酶的消化降低了产物的降压活性。泥鳅多肽属于底物型ACE抑制肽。     

基于定量构效关系制备火麻仁蛋白ACE抑制肽

高血压是引发心血管疾病的主要因素,经常服用降压的药物会产生副作用,因而安全、高效的食源性降压肽成为关注点。本研究建立了血管紧张素转换酶(ACE)抑制肽的定量构效关系(QSAR)模型,确定ACE抑制肽的结构与其活性间的关系。将模型结果辅以计算机虚拟酶切精确掌握蛋白水解位点,筛选合适的蛋白酶水解火麻仁蛋白定向制备ACE抑制肽,并测定最终水解物的抑制效果。结果表明：基于二肽建立的SVM-AAindex模型具有最佳的预测性能(R²为0.81,RMSE为0.53),且当二肽C端氨基酸为疏水性和芳香族氨基酸时具有较强的ACE抑制效果。蛋白质组分分析发现火麻仁蛋白含有34.60%的疏水性氨基酸和芳香族氨基酸是制备ACE抑制肽的良好来源。选择虚拟酶切产生较多短肽和生物活性肽的碱性蛋白酶和枯草杆菌蛋白酶对火麻仁蛋白进行定向水解,获得的最终水解液的ACE抑制IC50值分别为1.89和2.30 mg/mL。本研究建立了一种高效精准的制备火麻仁蛋白ACE抑制肽的方法,在降血压药物上具有很好的应用前景。     

食物中一些降压的生物活性物质及其降压机理

食源性降压活性物质由于无毒副作用而备受重视。本文就目前研究较多的三种食源性降压活性物质大豆574'-三羟基异黄酮、蒜素及ACE抑制肽及其降压机理作一综述。     

食物中一些降压的生物活性物质及其降机理

食源性降压活性物质由于无毒副作用而备受重视.本文就目前研究较多的三种食源性降压活性物质大豆5,7,4′三羟基异黄酮、蒜素及ACE抑制肽及其降压机理作一综述.     

大豆降压肽研究进展

从高血压的形成机理,以及能够有效调节血压作用的ACE抑制肽的结构和功能入手,综述了食源性降压肽--大豆降血压肽的研究现状,提出了目前研究中需要解决的一些问题,阐述了大豆降压肽的开发价值和应用前景.     

食源性低聚肽的血管紧张素转化酶(ACE)抑制作用

在对海洋胶原低聚肽、乌鸡低聚肽、玉米低聚肽、小麦低聚肽、大豆低聚肽的基础理化成分和分子量分布进行分析的基础上,对其ACE抑制作用进行了考察。组成分析显示:5种食源性低聚肽中蛋白质含量很高,均达到了85%以上;分子量大多为1000 u以下(均在85%以上),主要分布在132~576 u范围内。ACE抑制作用实验结果显示:这5种食源性低聚肽的ACE抑制活性均呈显著的量效关系,半抑制浓度IC_(50)值在0.53-2.76 mg/mL之间,其中玉米低聚肽的ACE抑制作用最强,乌鸡低聚肽的ACE抑制作用最弱。研究明确了食源性低聚肽的ACE抑制作用,为其作为降血压保健食品的开发利用提供了一定的理论支持。     

Antihypertensive mechanism of a peptide-enriched soy sauce-like seasoning: the active constituents and its suppressive effect on renin-angiotensin-aldosterone system

We previously reported that a peptide-enriched soy sauce-like seasoning called fermented soybean seasoning (FSS) demonstrated antihypertensive effects both in spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats. Angiotensin I-converting enzyme (ACE) inhibitory substances (9 kinds of dipeptides and a nicotianamine) were identified from FSS. In the present study, we clarified the mechanisms underlying the antihypertensive effects of FSS in SHR. FSS was divided into the nicotianamine fraction and the peptide fraction. The peptide fraction was found to exert a more prevalent antihypertensive effect than the nicotianamine fraction in SHR. Among the peptides, we identified Gly-Tyr and Ser-Tyr as the 2 primary substances in FSS that contributed to the antihypertensive effect in SHR. These peptides were neither degraded by acid nor gastrointestinal proteases, and were absorbed into the circulating blood. FSS (2000 mg/kg) exerted ACE inhibitory activity in the lung of rats and provided a decrease (P= 0.0067) in the level of serum aldosterone after a single oral administration in SHR, resulting in the antihypertensive effect. The antihypertensive mechanism was found to be similar to therapeutic ACE inhibitors and other food-derived ACE inhibitory peptides, which are in wide use and are recognized as safe.     

鮰鱼皮明胶ACE抑制肽降血压活性的研究

鮰鱼皮为斑点叉尾鮰鱼片加工的主要副产物,利用鮰鱼皮明胶制备降血压肽(ACE抑制肽)可为鮰鱼皮的高值化利用提供参考。本文通过对原发性高血压大鼠(SHR)进行一次性及长期给药(28 d)实验,研究鮰鱼皮明胶ACE抑制肽(Mr3000 Da)的降血压作用,并测定大鼠血清和肺组织中的ACE活性和Ang II含量。实验结果表明:一次性给药和长期灌胃给药鮰鱼皮明胶ACE抑制肽均对SHR大鼠有显著降血压作用,降血压效果呈剂量依赖性;高剂量组SHR大鼠灌胃给药2 h后,其收缩压由206 mmHg降至159 mmHg;高剂量组SHR大鼠经长期灌胃给药10 d后,血压一直保持在155 mmHg左右;同时,鮰鱼皮明胶ACE抑制肽对正常血压大鼠的降血压作用不显著。鮰鱼皮明胶ACE抑制肽对SHR大鼠血清和肺组织中的ACE活性有显著的抑制作用,从而使大鼠血清和肺组织中Ang II含量显著降低,而对正常血压的SD大鼠的血清和肺组织中ACE活性和Ang II含量影响不显著。     

Food‐Originating ACE Inhibitors,Including Antihypertensive Peptides,as Preventive Food Components in Blood Pressure Reduction

This work is a literature overview on angiotensin‐converting enzyme (ACE) inhibitory/antihypertensive peptides in food protein sources. The following aspects related to peptides with the above‐mentioned bioactivity are discussed: (i) mechanism of action of ACE, (ii) the structural character of ACE inhibitors/antihypertensive peptide sequences determined by different methods, including quantitative structure–activity relationship studies, (iii) their food sources, (iv) absorption of peptides, (v) in vitro and in vivo approaches involved in the production and potential release of peptide ACE inhibitors as well as in silico methods applied in research concerning peptides.     

Angiotensin I-converting enzyme inhibitory activity of Acetes chinensis peptic hydrolysate and its antihypertensive effect in spontaneously hypertensive rats

Peptic hydrolysate with angiotensin I-converting enzyme (ACE) inhibitory activity was prepared from Acetes chinensis . The 3 kDa ultrafiltration filtrates (UF-IV) of the desalted hydrolysate exerted a potent ACE inhibitory activity with IC50 being 0.67 mg mL⁻¹. The fractions with molecular weight located between 611 and 240 Da achieved a total percentage of 63.6% in the UF-IV, with a mean peptide length of about 5.6–2.1. Gastrointestinal digestions were simulated on the hydrolysate and UF-IV and addressed their effect on the ACE inhibitory activity. The ACE inhibitory activity of the UF-IV could survive or be maintained in active form by simulated gastrointestinal digestion. Furthermore, the UF-IV exerted potent antihypertensive effect after oral administrations were given to spontaneously hypertensive rats (SHR) at a dose of 900 mg kg⁻¹ body weight. In conclusion, the UF-IV could serve as useful antihypertensive peptides in the prevention and treatment of hypertension and other associated disorders.     

Identification of an Angiotensin I-converting Enzyme Inhibitory Peptides from Protein Hydrolysates by a Soybean Protease and the Antihypertensive Effects of Hydrolysates in 4 Spontaneously Hypertensive Model Rats

ABSTRACT: Our previous study demonstrated that, because of its substrate specificity, protein hydrolysates by protease D3, which is originated from soybean, exhibited the prominent property of being less bitter than other enzymatic hydrolysates. In the 1st experiment in this series, angiotensin I-converting enzyme (ACE) inhibitory peptides from soy protein hydrolysate by D3 were identified by the establishment of a novel and effective peptide identification method. The amino acid sequences of candidate ACE inhibitory peptides were determined by electrospray ionization mass/mass spectrometry (MS/MS) analysis after rough purification of the samples with gel filtration chromatography and reverse-phase chromatography. Some of the candidate peptides had amino acid sequences that showed homology with those of the reported ACE inhibitory peptides. Then, 8 types of novel candidate peptides were synthesized according to a solid-phase method, and their ACE inhibitory activity was confirmed as the IC₅₀ value. The most potent inhibitor was NWGPLV (IC₅₀= 21 μ M ). In the 2nd experiment, the antihypertensive activity of protein hydrolysates by D3 was investigated in spontaneously hypertensive model rats (SHRs). The dose-dependent antihypertensive effect of soy protein hydrolysate was confirmed, and systolic blood pressure was significantly reduced after the oral administration of doses exceeding 100 mg/kg. Casein hydrolysate was found to have the most potent effects on suppressing blood pressure as well as ACE inhibitory activity among the various food protein hydrolysates studied because of the primary structure of casein. These results indicate that hydrolysates by D3 could be a useful food ingredient because it has the physiological function (antihypertensive activity).     

Antihypertensive effect of an angiotensin converting enzyme inhibitory peptide from enzyme modified cheese

Two angiotensin converting enzyme (ACE)-inhibitory peptides were isolated from enzyme modified cheese (EMC) and their amino acid sequences were identified as Leu-Gln-Pro and Met-Ala-Pro. The EMC was prepared by a combination of Protease N, Umamizyme, and Flavourzyme 500L. Both peptides were derived from beta-casein, f 88-90 and f 102-104, respectively. Met-Ala-Pro showed strong ACE inhibitory activity (IC50=0.8 mum) and antihypertensive activity in spontaneously hypertensive rats (SHR) after single oral administration. The IC50 value of Met-Ala-Pro was not affected by pre-incubation with ACE, suggesting that this peptide was a true ACE-inhibitory peptide. We report here, for the first time antihypertensive peptides from EMC.     

食品蛋白降血压肽及其研究进展

食品降血压肽已成为生物活性肽研究领域的热点。综述血管紧张素转化酶对血压的调节作用、降血压肽的降血压机理和降血压肽结构与抑制ACE的关系，介绍了食品降血压肽的制备及分离纯化方法。