用玉米大豆复配蛋白制备降血压肽水解酶筛选研究

为了综合利用玉米、大豆加工副产品，使其营养价值、生物活性提高，用三种酶酶法改性复配蛋白质后，采用试剂盒测定了酶解肽抑制血管紧张素Ⅰ转化酶（ACE）的活性，并用HPLC分析了原料中氨基酸的组成。结果表明：复配蛋白质适合用作生产抑制ACE活性肽的原料；中性蛋白酶是一种用于玉米、大豆蛋白制备降血压肽的较理想的酶，当[E]／[S]为0．5％，料液比为1：15，水解时间为3h时，肽的ACE抑制率最高可达99％。     

动物与临床试验——评价大豆低聚肽的降血压效果

为了检验大豆低聚肽的降血压效果,首先进行了动物试验,选择SHR(自发性高血压)大鼠30只,其中21只为雌性大鼠,9只为雄性大鼠。喂养方法:大豆低聚肽加入饮水中服用,并辅以乳粉;对照组仅给乳粉和饮水。实验期间,每天下午测定血压(SBP)。结果表明,大豆低聚肽的降血压作用很明显。服药3d后,实验组的血压与对照组的血压相比低30mmHg。剂量对降血压效应也有影响。低剂量能使血压下降到较低的值,但是随后效应有反弹;高剂量则可较早地降低血压,并且在较长的时间内保持平衡。临床实验研究按照中国高血压指南标准选择原发性高血压患者40例,平均年龄为51.66±11.35岁,分别在服用大豆低聚肽前和1个月后测定血压、心率,记录心电图等和血液中相关生化指标。研究认为,服用大豆低聚肽可能会降低原发性高血压患者的血压,其机制可能与其对血压紧张素转化酶(Angiotensinconvertingenzyme,ACE)的抑制有关。     

食物中血管紧张素转化酶抑制肽的研究进展

人体内血管紧张素转化酶（AcE）的活性是影响血压的重要因素。利用蛋白酶水解食物中蛋白得到的血管紧张素转化酶抑制肽（AHPS），不仅能够抑制ACE活性、降压明显，而且具有安全性好，成本低，易吸收等特点，越来越受到人们的关注。主要综述了血管紧张素转化酶抑制肽（AcEI）的降压机理、来源、结构分类、生理活性、制备与精制以及前景展望。     

含血管紧张素转化酶抑制肽的酪蛋白水解物与紫薯提取物联用对原发性高血压大鼠血压的影响

以富含血管紧张素转化酶（angiotensin converting enzyme,ACE）抑制肽的酪蛋白水解物和富含花青素的紫薯提取物为原料,灌胃12 周龄雄性原发性高血压大鼠（spontaneously hypertensive rats,SHR）和正常雄性Wistar大鼠,研究富含ACE抑制肽的酪蛋白水解物和紫薯提取物对SHR血压的影响。用不同剂量的酪蛋白水解物（10、20、30、40 mg/kg,以体质量计,下同）和紫薯提取物（5.4、10.8、21.6、32.4 mg/kg,花青素含量为9.25%）分别灌胃SHR和Wistar大鼠。然后选用酪蛋白水解物的2 个剂量组分别与紫薯提取物的3 个剂量组联合灌胃SHR。用智能无创血压计测量SHR血压变化。结果表明：富含ACE抑制肽的酪蛋白水解物和富含花青素的紫薯提取物,在实验灌胃剂量范围内均具有较好的降压效果,而且两者联用进行单次灌胃后降压效果显著提高（P＜0.05）。其中酪蛋白水解物（10 mg/kg）分别与紫薯提取物3 个剂量（5.4、10.8、21.6 mg/kg）联合灌胃SHR后4 h或者5 h,血压分别降低了（24.67±4.46）、（28.47±3.96）、（41.51±4.89） mmHg。用酪蛋白水解物（20 mg/kg）分别与紫薯提取物的3 个剂量（5.4、10.8、21.6 mg/kg）联合灌胃SHR后5 h或者6 h,SHR血压分别降低了（38.03±3.46）、（43.92±2.92）、（47.20±4.31） mmHg。两者联用灌胃后对Wistar正常大鼠的血压无影响。另外,酪蛋白水解物2 个剂量（10、20 mg/kg）和紫薯提取物（10.8 mg/kg）分别联合使用,间隔4 h灌胃1 次,每天灌胃2 次,SHR大鼠血压较灌胃前分别降低了（28.20±3.02）、（43.54±2.55） mmHg,而且能较长时间维持在较低血压水平。因此,富含ACE抑制肽的酪蛋白水解物和富含花青素的紫薯提取物联合食用对SHR的降压具有显著效果。     

菜籽肽的制备及其对大鼠血管紧张素Ⅰ转换酶(ACE)活性的影响

目的：分离菜籽清蛋白水解物并研究混合肽及级分对大鼠血管紧张素I转换酶（ACE）活性的影响。方法：采用葡聚糖凝胶过滤色谱（sephadexG-25）分离菜籽肽；离体培养检测血管紧张素Ⅰ转换酶（ACE）活性。结果：菜籽肽（RSP-R）及分离的三个级分（RSP-Ⅰ、Ⅱ和Ⅲ）对高血压大鼠ACE活性均有明显抑制作用，其中级分Ⅲ抑制能力最强。结论：菜籽清蛋白水解多肽具有抑制ACE活性能力，这一结果有助于菜籽清蛋白的广泛应用。     

玉米大豆复合肽体内ACE抑制活性研究

为了考察玉米大豆复合肽的体内抑制血管紧张素转化酶(ACE)活性,采用自发性高血压鼠(SHR)为模型,进行了一次性给药和长期给药动物试验,并以卡托普利(Captopril)作为阳性对照,采用尾袖法测定SHR的血压变化.结果表明:一次性给药后,中(50 mg/kg·bw)、高剂量(100 mg/kg·bw)玉米大豆复合肽(CSP)组的降血压作用可一直持续3 h,血压值降低达显著水平(P<0.05);长期试验中,每日给予CSP,12 d后开始,与模型组SHR比较,中剂量组(25 mg/kg·bw)和高剂量组(50 mg/kg·bw)的SHR血压值均明显降低(P<0.05～P<0.01);高剂量(50 mg/kg·bw)给肽组的降血压效果略好于Captopril组,并对正常大鼠的血压无影响;CSP对大鼠有增加体重的作用.因此CSP对SHR具有良好的短期和长期降血压作用,并对正常血压大鼠无影响;CSP同时是大鼠良好的营养剂.     

富硒大豆低聚肽降血压作用的研究

为了研究富硒大豆低聚肽在降血压方面的作用,本研究采用5周龄SD雄性大鼠60只,随机分为4组,按设计进行饲喂实验,测定各试验大鼠的体重和血压,饲喂4周,停喂次日处死所有大鼠,测定血清和肺组织中ACE活力及血清中K、Na、Se的含量。结果显示:富硒大豆低聚肽能促进试验大鼠的体重增加,降低大鼠血清中ACE活性,但对肺组织ACE活性无显著影响,能导致大鼠血清中Na离子浓度下降、Se含量增加。说明富硒大豆低聚肽具有降低SHR血压的作用,这种作用是Se和大豆低聚肽共同作用的结果,除与ACE活力被抑制有关外,还可能与导致大鼠体内Na+浓度下降、Se含量增加有关。     

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。     

食品降血压肽的比较与评价方法

血管紧张素转换酶 (angiotensinⅠ convertingenzyme ,简写为ACE)抑制剂可以抑制ACE的活性 ,降低血压。目前已经知道许多食品如 :乳蛋白质、酸奶、干酪、沙丁鱼、鸡蛋、玉米胚乳等中含有ACE抑制肽。其获取方法主要通过酶法和微生物法 ,一般通过体外测定和动物实验来评价ACE抑制剂的抑制活性和抗高血压作用     

葛根降血压茶的制备及对自发性高血压大鼠的降压作用

目的：制备具有较高血管紧张素转换酶(ACE)活性体外抑制率的冠突散囊菌发酵茶,并考察发酵茶液对自发性高血压大鼠(SHR)的急性降压作用。方法：考察葛根添加量、基质含水量和孢子悬浮液对ACE酶活性体外抑制率的影响,并采用正交试验进行发酵工艺优化;水提法制备发酵茶液,选择SHR模型研究发酵茶的降血压作用。结果：最优发酵工艺为20 g绿茶中添加2 g葛根量,20%基质含水量,5%孢子悬浮液接种量。与对照组相比,不同剂量的葛根降血压茶对SHR在24 h内均有降低收缩压和舒张压作用。结论：300~600 mg/kg日用剂量的葛根降血压茶的急性降压效果最显著,可在短期内降低SHR血压。     

Angiotensin‐I‐Converting Enzyme Inhibitory Activities and In Vivo Antihypertensive Effects of Sardine Protein Hydrolysate

In our previous study, an antihypertensive protein hydrolysate was prepared from sardine. This study aimed to investigate the composition of sardine protein hydrolysate (SPH) and it's in vivo antihypertensive effect. SPH was separated sequentially with ultrafiltration and size exclusion chromatography. Fractions with high angiotensin‐I‐converting enzyme (ACE) inhibitory activity were further analyzed with RP‐HPLC and amino acids analysis. Then, SPH was individually oral administrated to spontaneously hypertensive rats (SHR) and normotensive wistar kyoto rats (WKY) for 4 wk. After treatment, the systolic blood pressure (SBP), organ index, oxidative status, serum ACE activity, and serum angiotensin‐II (ANG‐II) of all the rats were determined. According to the separation and analysis results, 3 main fractions with high ACE‐inhibitory activity were obtained with different amino acids composition. The animal experiments results showed that SPH could significantly reduce SBP (P < 0.05 or P < 0.01) within 4 h after a single oral administration. After a chronic oral administration, a steady state of SBP in SHR rats was attained. The heart weight index and left ventricular weight index were significantly reduced (P < 0.05) in SPH‐treated SHR rats. The malonyldialdehyde (MDA) levels in organs and serum, serum ACE activity, and serum ANG‐II concentration in SPH‐treated SHR rats were significantly lowered (P < 0.05 or P < 0.01) as compared to their controls. Meanwhile there was no significant effect (P > 0.05) on those parameters in WKY rats. These results indicate that SPH can decrease blood pressure in SHR rats and not in WKY rats.     

Antihypertensive and antioxidant effects of the Graptopetalum paraguayense E. Walther extract in spontaneously hypertensive rats

BACKGROUND: Our previous in vitro study showed that 50% ethanolic extract of Graptopetalum paraguayense E. Walther (GE50) exhibited an inhibitory effect on angiotensin I converting enzyme (ACE). This study was aimed at evaluating the antihypertensive and antioxidant effects of GE50 extract on spontaneously hypertensive rats (SHR). RESULTS: Daily oral administration of GE50 extract (2.5 g kg⁻¹ body weight) for 4 weeks exhibited a significant decrease in blood pressure as well as ACE activity of tested tissues in SHR rats, while no significant change was found in normotensive Wistar Kyoto rats (WKY). For SHR, GE50 extract increased the total antioxidant status in the plasma and decreased malondialdehyde levels in all tested tissues. Furthermore, GE50 extract increased α‐tocopherol and glutathione levels in brain tissue, glutathione peroxidase and catalase activities in heart, as well as catalase activity in liver tissue. In WKY rats, GE50 extract only increased ascorbic acid level in liver tissue. CONCLUSION: The present study demonstrated that GE50 might serve as an antioxidant and an ACE inhibitor in convalescence from hypertension in rats. Copyright © 2009 Society of Chemical Industry     

Absorption-enhancing Treatments for Antihypertensive Activity of Oligopeptides from Tuna Cooking Juice: In Vivo Evaluation in Spontaneously Hypertensive Rats

ABSTRACT The aim of this study was to evaluate the absorption‐enhancing effect for antihypertensive activity of an angiotensin I‐converting enzyme (ACE) inhibitory oligopeptides in spontaneously hypertensive rats (SHR). The oligopeptides OA3, derived from tuna cooking juice, significantly reduced systolic blood pressure (SBP) in SHR at the doses of 0.5, 0.75, and 1.0 g/kg body weight; their efficacies were exhibited in a dose‐dependent manner. Emulsification, microencapsulation, and lipophilization were applied to enhance the antihyperten‐sive activity of OA3 at the dose of 0.5 g/kg body weight in SHR individually. Lipophilization revealed most effectively by 16 mm Hg in SBP in SHR 4 h after oral administration; the significant different effect lasted more than 6 h. Such efficacy is greater than that from no further treated OA3 with the dose of 1.0 g/kg body weight. Enhancing treatments by using 30% gum Arabic and 30% lecithin exhibited minor effects by 13 and 11 mm Hg, respectively. Results imply that these additional treatments could further enhance and extend the antihyperten‐sive effect of OA3 oligopeptides. This suggests that absorption‐enhancing treatments improve the bioavailability of oligopeptides to exhibit higher antihypertensive effect. Furthermore, these enhancing effects may be brought about by the changes in cell membrane permeation or the protection of oligopeptides.     

Angiotensin I Converting Enzyme (ACE) inhibitory activity and antihypertensive effects of grass carp peptides

In vitro and in vivo antihypertensive effects of grass carp peptides (GCP) were investigated. The amino acid composition and the angiotensinconverting enzyme inhibitory activity were evaluated using HPLC. GCP was administrated to spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKY) by single and long-term administration before blood pressure measurements. Plasma levels of angiotensin II (Ang II), rennin (RA), nitric oxide (NO), and plasma angiotensin I converting enzyme (ACE) activity were measured. The GCP molecular weight was between 725 and 1,228 Da with high levels of Leu, Asp, Phe, Gly, and Pro. The in vitro IC₅₀ value was 0.23 mg/mL. GCP lowered SHR blood pressure dose and timedependently. Little change occurred in WKY. The plasma level of Ang II and the ACE activity decreased. SHR RA and NO concentrations in plasma increased. The antihypertensive effect of GCP was associated with NO regulation and the rennin-angiotensin system.     

Mechanisms for antihypertensive effect of CocoanOX, a polyphenol-rich cocoa powder, in spontaneously hypertensive rats

We investigate the mechanisms involved in the long-term antihypertensive effect of a polyphenol-rich cocoa powder, named CocoanOX® (CCX), in spontaneously hypertensive rats (SHR). We have carried out two different batches of experiments. For the first batch of experiments, forty 3 week-old male SHR were randomly divided with ad libitum intake into four groups of 10 animals, that respectively received the following drinking fluids up to the 20th week of life (treatment period): tap water (control), CCX 100 mg/kg/day, CCX 200 mg/kg/day and CCX 400 mg/kg/day. Five 20 week-old rats of each group were sacrificed by decapitation. From the 20th to 24th week of life all the remaining animals were given tap water (follow-up period), and all of them were sacrificed at the end of the follow-up period. Plasma malondialdehyde (MDA), reduced glutathione in the liver, plasma and aorta angiotensin converting enzyme (ACE) activity and plasma angiotensin II were determined in all the sacrificed SHR that were included in this batch of experiments. Plasma MDA decreased and liver reduced glutathione increased in the 20 week-old CCX treated SHR. These effects were not observed in the rats that were sacrificed after the follow-up period. CCX treatment did not modify aorta ACE activity, but the activity of ACE and the levels of angiotensin II increased in the plasma of the SHR treated with the highest dose of CCX. ACE activity returned to basal values in the SHR that were sacrificed after the follow-up period. However, angiotensin II levels were slightly higher after withdrawal of CCX.For the second batch of experiments we used aorta rings obtained from untreated SHR, and we evaluated the relaxation caused by CCX in different aorta preparations. CCX relaxed the intact aorta preparations but this cocoa did not relax the endothelium-denuded aorta rings from the untreated SHR. l-NAME, but not indomethacin, inhibited the relaxation caused by CCX in the SHR aorta rings. We postulate that the antihypertensive effect of CCX might be mediated by an improvement of endothelial release of nitric oxide and by a reduction of oxidative stress. The inhibition of ACE could be implicated in the antihypertensive effect of CCX.     

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。     

HYPOTENSIVE ACTIVITY OF MUSCLE PROTEIN AND GLUTEN HYDROLYSATES OBTAINED BY PROTEASE TREATMENT

Protein hydrolysates obtained by treatment with papain, trypsin, chymotrypsin and actinase all exhibited inhibitory activity (IC50: 3.4–41.8 mg%) toward angiotensin‐converting enzyme (ACE) (EC 3.4.15.1). In particular, the protein hydrolysate obtained by treatment with papain showed the highest inhibitory activity (3.7–5.3 mg%). The ACE inhibitory activity of the gluten hydrolysate obtained with actinase was mainly due to peptides of less than 500 Da in molecular mass. On the other hand, the ACE inhibitory activity of the myofibrillar protein hydrolysate obtained with papain was due to peptides of both less and more than 500 Da in molecular mass. The blood pressure of spontaneously hypertensive rats (SHR) administered the myofibrillar protein hydrolysate was significantly reduced at 2 h after administration. The blood pressure of SHR was also reduced at 2 h after administration of the gluten hydrolysate, and this effect continued until 6 h. These hydrolysates may potentially be useful as antihypertensive food materials.