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。     

具有临床降血压功效的乳源三肽的研究进展

高血压是人类健康的一大杀手,食品来源的血管紧张素转换酶抑制肽（angiotensin-converting enzyme inhibitory peptides,ACEIPs）因为安全性高、无毒副作用等显著优势而成为合成血管紧张素转换酶（angiotensin-converting enzyme,ACE）抑制剂类降血压药物的潜在替代品。目前已有大量基于体外ACE抑制活性的降血压肽被分离鉴定,但是经过临床研究证实对人体具有明确体内降血压功效的仅有Ile-Pro-Pro（IPP）、Val-Pro-Pro（VPP）和Leu-Pro-Pro（LPP）等少数几种。由于上述3 种三肽最初在酸牛奶中被发现,因此被合称为乳源三肽（以下简称乳三肽）,目前国外已有多种基于乳三肽的降血压功能食品上市,其降血压功效已得到了充分验证,但国内尚未发现类似产品。本文就乳三肽的功效、安全性、制备方法和新来源等进行了综述,并对现有关于乳三肽的专利进行了总结,以期为推动我国基于乳三肽第三代降血压功能食品的开发提供参考。     

Activity and bioavailability of food protein-derived angiotensin-I-converting enzyme–inhibitory peptides

Angiotensin-I-converting enzyme (ACE) inhibitory peptides are able to inhibit the activity of ACE, which is the key enzymatic factor mediating systemic hypertension. ACE-inhibitory peptides can be obtained from edible proteins and have the function of antihypertension. The amino acid sequences and the secondary structures of ACE-inhibitory peptides determine the inhibitory activities and stability. The resistance of ACE-inhibitory peptides to digestive enzymes and peptidase affect their antihypertensive bioactivity in vivo. In this paper, the mechanism of ACE-inhibition, sources of the inhibitory peptides, structure–activity relationships, stability during digestion, absorption and transportation of ACE-inhibitory peptides, and consumption of ACE-inhibitory peptides are reviewed, which provide guidance to the development of new functional foods and production of antihypertensive nutraceuticals and pharmaceuticals.     

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。     

利用海洋生物蛋白制备ACE抑制肽的研究进展

血管紧张素转化酶(angiotensin convert enzyme,ACE)在血压调节方面起着重要作用,当其受到抑制时血压就会降低。本文综述了A C E抑制肽的降压原理、活性检测方法、分离提纯和海洋生物蛋白源A C E抑制肽的国内外最新研究进展,并对其应用前景进行了展望。     

南瓜籽蛋白源血管紧张素转化酶抑制肽的制备及其降血压活性

食源性降血压肽在调节机体血压过程中发挥着一定的积极作用。本实验采用碱性蛋白酶水解南瓜籽蛋白,水解物经膜分离获得血管紧张素转化酶（angiotensin converting enzyme,ACE）抑制肽,通过质谱鉴定其结构,并采用抑制动力学和分子对接方法研究ACE抑制肽的活性机制;此外,通过ACE抑制活性实验、自发性高血压大鼠（spontaneously hypertensive rats,SHRs）模型等评价南瓜籽蛋白水解物、膜分离组分以及南瓜籽肽的降血压活性。结果表明,低于1 kDa南瓜籽蛋白水解物组分ACE抑制活性较好,1 mg/mL下ACE抑制率为46.22%,100 mg/kg mb 剂量下灌胃SHRs 6 h后收缩压可以降低21.42 mm Hg;鉴定出9 个ACE抑制肽（LLV、LVF、LTPL、SVLF、LLPQ、MLPL、LLPGF、VLLPE和RFPLL）,其中RFPLL、LLPGF、MLPL和LVF具有较好的ACE抑制活性,半抑制浓度均低于1 mmol/L;RFPLL和LVF具有较好的降血压活性,30 mg/kg mb剂量下灌胃6 h后SHRs的收缩压降低量分别为37.0 mm Hg和22.2 mm Hg,SHRs的舒张压降低量分别为17.0 mm Hg和11.2 mm Hg;RFPLL、LLPGF、MLPL和LVF可以很好地对接ACE的活性中心,RFPLL是ACE混合型抑制剂,MLPL对ACE的抑制模式可能是竞争型抑制,LLPGF、LVF可能是ACE的非竞争型抑制剂。综上,低于1 kDa南瓜籽蛋白水解物是一种良好的降血压功能食品原料,其中RFPLL和LVF可用于降血压功能食品或者药品的开发原料。     

ACE抑制肽构效关系及其酶法制备的研究进展

高血压是一种全球性的公共健康问题。血管紧张素转换酶(angiotensin converting enzyme,ACE)作为一种二肽缩肽酶,通过肾素-血管紧张素系统和激肽释放酶-激肽系统(kallikrein-kinin system,KKS)对血压进行调节。近年来,已有许多从各种食源蛋白中获得ACE抑制肽的研究报道。相比于化学合成药物,食源性蛋白获得的ACE抑制肽在治疗高血压方面更具安全性和温和性。许多研究已经探讨了食源性降压肽的构效关系,尤其是多肽一级序列对活性的影响。目前,最常用于制备ACE抑制肽的方式是酶催化水解蛋白,包括使用单酶或复合酶对蛋白进行水解。本文将主要对ACE抑制肽构效关系和酶法制备ACE抑制肽的研究进展进行综述,以期为获得优良的ACE抑制肽产品提供理论指导。     

乳及乳制品中的抗高血压活性肽

论述了乳及乳制品中的抗高血压活性肽的分离纯化、构性关系、对血管紧张素转换酶的抑制活性和抗高血压机理，以及其在体内的吸收特性。展望了乳源抗高血压肽的应用前景。     

乳源ACE抑制肽的制备及应用

近年来高血压成为威胁人类健康的第一大慢性病,由于常规降压药物对人体的损害,食源性降压肽成为研究的热点。目前研究发现了多种乳源ACE抑制肽,并得到应用。本文综述乳源ACE抑制肽的制备、纯化及应用现状。     

食物源ACE抑制肽的生产及构效关系研究进展

生物活性肽是蛋白质中隐藏着的可在体内发挥一定生理功能的活性肽段。目前已从食物蛋白中获得了具有免疫调节、抑菌、抗病毒、抗肿瘤、抗血栓形成、抗高血压等功能的多肽,其中血管紧张素转化酶(ACE)抑制肽是研究热点之一。ACE通过产具有升压作用的血管紧张素Ⅱ和降解扩张血管的舒缓激肽在调节血压中发挥着重要作用。ACE抑制肽可通过消化道水解、发酵和熟化过程、体外酶解和遗传重组方法而获得,并可作为功能因子添加到功能食品中,相关产品已上市或研发中。本文对ACE抑制肽的生产及其构效关系研究进展等进行综述。     

Bioactive Peptides Derived from Seaweed Protein and Their Health Benefits: Antihypertensive,Antioxidant, and Antidiabetic Properties

Cardiovascular diseases and diabetes are the biggest causes of death globally. Therefore, prevention of these diseases is a focus of pharmaceuticals and functional food manufacturers. This review summarizes recent research trends and scientific knowledge in seaweed protein‐derived peptides with particular emphasis on production, isolation and potential health impacts in prevention of hypertension, diabetes and oxidative stress. The current status and future prospects of bioactive peptides are also discussed. Bioactive peptides have strong potential for use in therapeutic drug and functional food formulation in health management strategy, especially cardiovascular disease and diabetes. Seaweeds can be used as sustainable protein sources in the production of these peptide‐based drugs and functional foods for preventing such diseases. Many studies have reported that peptides showing angiotensin converting enzyme inhibition, antihypertensive, antioxidative and antidiabetics activities, have been successfully isolated from seaweed. However, further research is needed in large‐scale production of these peptides, efficient isolation methods, interactions with functional foods and other pharmaceuticals, and their ease to digestion in in vivo studies and safety to validate the health benefits of these peptides.     

Bioactive Natural Constituents from Food Sources—Potential Use in Hypertension Prevention and Treatment

Prevention and management of hypertension are the major public health challenges worldwide. Uncontrolled high blood pressure may lead to a shortened life expectancy and a higher morbidity due to a high risk of cardiovascular complications such as coronary heart disease (which leads to heart attack) and stroke, congestive heart failure, heart rhythm irregularities, and kidney failure etc. In recent years, it has been recognized that many dietary constituents may contribute to human cardiovascular health. There has been an increased focus on identifying these natural components of foods, describing their physiological activities and mechanisms of actions. Grain, vegetables, fruits, milk, cheese, meat, chicken, egg, fish, soybean, tea, wine, mushrooms, and lactic acid bacteria are various food sources with potential antihypertensive effects. Their main bioactive constituents include angiotensin I-converting enzyme (ACE) inhibitory peptides, vitamins C and E, flavonoids, flavanols, cathecins, anthocyanins, phenolic acids, polyphenols, tannins, resveratrol, polysaccharides, fiber, saponin, sterols, as well as K, Ca, and P. They may reduce blood pressure by different mechanisms, such as ACE inhibition effect, antioxidant, vasodilatory, opiate-like, Ca²⁺ channel blocking, and chymase inhibitory activities. These functional foods may provide new therapeutic applications for hypertension prevention and treatment, and contribute to a healthy cardiovascular population. The present review summarizes the antihypertensive food sources and their bioactive constituents, as well as physiological mechanisms of dietary products, especially focusing on ACE inhibitory activity.     

大豆分离蛋白ACE活性抑制肽的研究

研究了预处理条件对大豆分离蛋白水解效果的影响,热处理与微波辅助处理相结合能显著提高蛋白酶的水解效率.比较了6种酶解大豆蛋白产物的ACE抑制活性,选择碱性蛋白酶为最佳水解用酶,并优化了酶解条件.研究了8种大孔树脂对水解产物精制效果,结果表明:经D3520型大孔吸附树脂精制后,水解产物脱盐率89.4%,肽回收率90.6%,ACE抑制活性达84.1%.经HPLC法测定,大豆分离蛋白ACE活性抑制肽混合物分子质量主要分布在200～800 ku之间.     

降血压肽分离的研究现状与展望

通过凝胶过滤色谱、反相高效液相色谱（RP-HPLC）等方法将不同来源的降血压肽进行分离，以得到结构明确的短肽片断，之后进行活性检测，从而为降血压机理的研究以及高血压的治疗提供了途径，并有望开发成降血压类功能食品。本论文概述了不同食物来源降血压肽国内外分离提纯研究的意义、现状及展望。     

Purification and characterization of angiotensin I converting enzyme inhibitory peptides from jellyfish Rhopilema esculentum

Two angiotensin I converting enzyme (ACE) inhibitory peptides were isolated from jellyfish Rhopilema esculentum protein hydrolysates prepared with pepsin and papain. Consecutive purification methods, including ion-exchange chromatography, size-exclusion chromatography and reverse-phase high-performance liquid chromatography, were used for isolation of ACE inhibitory peptides. The amino acid sequence of the peptides was identified as Gln-Pro-Gly-Pro-Thr and Gly-Asp-Ile-Gly-Tyr, respectively, and the IC₅₀ value of the purified peptides for ACE inhibitory activity was 80.67 μM and 32.56 μM. The purified peptides were evaluated for the antihypertensive effect in spontaneously hypertensive rats (SHR) after oral administration. Blood pressure decreased significantly after ingestion of the peptides. The results suggest that peptides derived from jellyfish R. esculentum may be beneficial as antihypertensive compounds in functional food resources.     

发酵调味品中血管紧张素转化酶抑制肽的研究进展

发酵调味品是采用微生物发酵的方法,生产具有食品调味和佐餐功能的一类食品。因微生物发酵原料和菌种的不同,所产生的调味品功能有所差异,蛋白类原料在微生物酶的作用下,能够产生相对较多的血管紧张素转化酶（ACE）抑制肽。ACE抑制肽是一类能抑制血管紧张素调节酶活性的多肽物质,可以起到预防或治疗高血压的作用。该研究通过对目前发酵调味食品ACE抑制肽的来源、制备方法、分离纯化方法等进行了介绍,并分析了发酵调味品ACE抑制肽今后的研究发展方向和产业发展趋势。     

Effects of natural peptides from food proteins on angiotensin converting enzyme activity and hypertension

Cardiovascular diseases are the leading cause of death. The underlying pathophysiology is largely contributed by an overactivation of the renin-angiotensin-aldosterone-system (RAAS). Herein, angiotensin II (AngII) is a key mediator not only in blood pressure control and vascular tone regulation, but also involved in inflammation, endothelial dysfunction, atherosclerosis, hypertension and congestive heart failure. Since more than three decades suppression of AngII generation by inhibition of the angiotensin-converting enzyme (ACE) or blockade of the AngII-receptor has shown clinical benefit by reducing hypertension, atherosclerosis and other inflammation-associated cardiovascular diseases. Besides pharmaceutical ACE-inhibitors some natural peptides derived from food proteins reduce in vitro ACE activity. Several animal studies and a few human clinical trials have shown antihypertensive effects of such peptides, which might be attractive as food additives to prevent age-related RAAS activation. However, their inhibitory potency on in vitro ACE activity does not always correlate with an antihypertensive impact. While some peptides with high inhibitory activity on ACE-activity in vitro show no antihypertensive effect in vivo, other peptides with only a moderate ACE inhibitory activity in vitro cause such effects. The explanation for this conflicting phenomenon between inhibitory activity and antihypertensive effect remains unclear to date. This review shall critically address the effects of natural peptides derived from different food proteins on the cardiovascular system and the possible underlying mechanisms. A central aspect will be to point to conceptual gaps in the current understanding of the action of these peptides with respect to in vivo blood pressure lowering effects.     

Antihypertensive activity of peptides identified in the in vitro gastrointestinal digest of pork meat

This study investigated the in vivo antihypertensive activity of three novel peptides identified in the in vitro digest of pork meat. These peptides were RPR, KAPVA and PTPVP and all of them showed significant antihypertensive activity after oral administration to spontaneously hypertensive rats, RPR being the peptide with the greatest in vivo activity. To our knowledge, this is the first report showing the in vivo antihypertensive action of the three peptides from nebulin (RPR) and titin (KAPVA and PTPVP), thus confirming their reported in vitro angiotensin I-converting enzyme (ACE) inhibitory activity. These findings suggest that pork meat could constitute a source of bioactive constituents that could be utilized in functional foods or nutraceuticals.     

Peptide inhibitors for angiotensin I-converting enzyme from enzymatic hydrolysates of porcine skeletal muscle proteins

Inhibitors of angiotensin I-converting enzyme (ACE) have been shown to have antihypertensive effects and have been utilized for pharmaceuticals and physiologically functional foods. In the present study, efforts were directed to find ACE inhibitory activities derived from muscle proteins. Porcine skeletal muscle proteins were hydrolyzed by eight proteases, and the inhibitory activities of the hydrolysates toward ACE were measured. Among the digests of the water-insoluble protein fraction prepared from muscle, thermolysin digest demonstrated the highest activity. Also, among hydrolysates of porcine myosin produced by the same enzymes, thermolysin digest showed the most potent inhibitory activity. Two ACE inhibitory peptides were purified from thermolysin digest of myosin. The sequences of these inhibitory peptides, named myopentapeptides A and B, were Met-Asn-Pro-Pro-Lys and Ile-Thr-Thr-Asn-Pro. These sequences were found in the primary structure of the myosin heavy chain. The concentrations of the peptides showing 50% inhibition values (IC(50)) of ACE were 945.5 and 549.0 μM, respectively. Also, six tripeptides, Met-Asn-Pro, Asn-Pro-Pro, Pro-Pro-Lys, Ile-Thr-Thr, Thr-Thr-Asn, and Thr-Asn-Pro, which have parts of the sequences of the myopentapeptides, demonstrated activity. Their IC(50) values were 66.6, 290.5, >1000, 678.2, 672.7, and 207.4 μM, respectively.     

富硒辣木叶蛋白ACE抑制肽的酶解工艺优化及活性研究

以富硒辣木叶为原料提取富硒辣木叶蛋白,通过单因素实验和响应面优化富硒辣木叶蛋白血管紧张素转化酶(ACE)抑制肽的制备工艺,并对最优酶解物的ACE抑制活性、氨基酸组成和硒含量进行分析表征.结果表明,富硒辣木叶蛋白ACE抑制肽的最佳酶解条件为时间3 h,pH7.5、酶底比0.23％、底物浓度5.97％、温度39.2℃.该条...