Angiotensin I converting enzyme(ACE)inhibitory activity and antihypertensive effects of rice peptides

In this paper,the antihypertension effect of rice peptide(RP)was studied.With spontaneously hypertensive rats(SHR)and Wistar Kyoto(WKY)as the research objects,RP disposable gastric and long-term gastric irrigation experiments were carried out and systolic blood pressure(SBP)was measured.At the end of the long-term gastric irrigation experiment,the content of nitric oxide(NO),angiotensin-converting enzyme(ACE),angiotensin II(Ang II)and renin in the plasma and the activity of ACE were determined.The results showed that RP could reduce systolic pressure of SHR and had time-dose dependence while high-dose RP signifi cantly reduced systolic pressure by 24.6 and 17.2 mm Hg,respectively after a single and long-term gastric irrigation test.RP also could inhibit the activity of ACE and increase the release of NO.These results suggested that the decompression mechanism of RP is likely to be related to the regulation of the renin-angiotensin system(RAS)and NO.

Antihypertensive effects of foods

Hypertension is one of the major risk factors for arteriosclerosis,which leads to cardiovascular disease and stroke.Several clinical trials revealed that control of the blood pressure is useful to reduce the morbidity and mortality associated with these diseases.However,the protective efficacy against these complications still remains at less than 50% even if the high blood pressure is treated by current medical drugs.Healthy diets are expected to not only prevent but also treat lifestyle-related diseases.Improvement of the dietary life,including lowsalt diets,appropriate alcohol consumption,and calorie restriction,is important for the prevention of hypertension.In addition,green tea,which has been drunk on a daily basis in Japan and China since ancient times,possesses an antihypertensive effect,and it was revealed that its components with this effect are catechins.Many studies have been performed on the antihypertensive effects of foods.Therefore,functional foods and their ingredients,reported to possess antihypertensive effects in animal experiments and human clinical trials,are summarized in this review.Blood pressure might be controlled by improvement of the daily eating habits based on evidence regarding these functional foods,and a healthy longevity can be expected.

Antihypertensive Properties on Spontaneously Hypertensive Rats of Peptide Hydrolysates from Silkworm Pupae Protein

Peptide hydrolysates of silkworm pupae protein with molecular weight of less than 5000 Da were prepared by ultrafiltration. The extracted peptide hydrolysates of silkworm pupae protein had inhibitory action on angiotensin-I-converting enzyme activity in vitro. The hydrolysates were orally administered to spontaneously hypertensive rats (SHR) in one period and long-term (four weeks). The results showed that the systolic blood pressure (SBP) of the treatment groups decreased in a dose-related manner. After one oral administration of silkworm protein hydrolysates with doses of 60, 20 and 5 mg/kg, the SBP of SHR decreased by 21.5, 13.8, and 9.0 mmHg in 1.5 h. After four weeks of the treatment in 80 mg/kg, the SBP decreased by 25 mmHg, with the antihypertensive activity close to 4 mg/kg of captopril;the SBP of the 40 mg/kg dose group also decreased by 17.5 mmHg. The peptide hydrolysate did not affect the SBP in normal, non-hypertensive rats in one period and long-term treatments. The acute toxicity research showed that the peptide hydrolysates were safe and without side effects. This research would be helpful in exploring the silkworm protein peptides as functional components for the antihypertension treatment.

Risk Factors Affecting Ischemic Stroke: A Potential Side Effect of Antihypertensive Drugs

Background: Stroke is a worldwide health problem, the world’s second-leading cause of death and third-leading cause of disability. Currently, the majority of stroke patients are ischemic stroke patients. It is necessary to evaluate risk factors to prevent ischemic stroke. Data and Methods: The risk factors for stroke in the previous fiscal year were analyzed. They were divided into nonmodifiable and modifiable factors. The probit and ordered probit models were used in the study, with 59341 and 50542 observations used in the estimation of the models, respectively. Results: Among the nonmodifiable factors, age, gender and cerebrovascular disease history are important risk factors. The history of cerebrovascular diseases is considered to be an especially important factor. Among the modifiable factors, taking antihypertensive drugs and recent large weight change are negative risk factors;however, sleeping well significantly reduces the probability of ischemic stroke. Conclusion: It is very important to ensure that medical personnel know a patient’s history of cerebrovascular diseases for proper treatments. Ischemic stroke might be considered an important side effect of antihypertensive drugs. Limitations: The dataset was observatory. There are various types of antihypertension drugs, and their effects are not analyzed.

Production of antihypertensive and antidiabetic peptide fractions from quinoa(Chenopodium quinoa Willd.)by electrodialysis with ultrafi ltration membranes

Processing bioactive peptides from natural sources using electrodialysis with ultrafiltration membranes(EDUF)have gained attention since it can fractionate in terms of their charge and molecular weight.Quinoa is a pseudo-cereal highlighted by its high protein content,amino acid profile and adapting growing conditions.The present work aimed at the production of quinoa peptides through fractionation using EDUF and to test the fractions according to antihypertensive and antidiabetic activity.Experimental data showed the production of peptides ranging between 0.4 and 1.5 k Da.Cationic(CQPF)(3.01%),anionic(AQPF)(1.18%)and the electrically neutral fraction quinoa protein hydrolysate(QPH)-EDUF(~95%)were obtained.In-vitro studies showed the highest glucose uptake modulation in L6 cell skeletal myoblasts in presence of QPH-EDUF and AQPF(17%and 11%)indicating potential antidiabetic activity.The antihypertensive effect studied in-vivo in spontaneously hypertensive rats(SHR),showed a decrease in systolic blood pressure in presence of the fractionated peptides,being 100 mg/kg a dose comparable to Captopril(positive control).These results contribute to the current knowledge of bioactive peptides from quinoa by reporting the relevance of EDUF as tool to produce selected peptide fractions.Nevertheless,further characterization is needed towards peptide sequencing,their respective role in the metabolism and scaling-up production using EDUF.

Interaction mechanism of egg white-derived ACE inhibitory peptide TNGIIR with ACE and its effect on the expression of ACE and AT1 receptor

The egg white-derived hexapeptide TNGIIR inhibits angiotensin-converting enzyme(ACE)activity in vitro.In this work,molecular docking revealed that TNGIIR established hydrogen bonds with the S1(Ala 354),S2(Gln 281,His 513,Tyr 520 and Lys 511)and S1(Glu 162)pockets of ACE.In addition,the potential antihypertensive effect of the oral administration of TNGIIR in spontaneously hypertensive rats(SHR)was investigated,as was the effect of this peptide on the mRNA expression of ACE and angiotensin type 1(AT1)and type 2(AT2)receptors in renal tissue.The oral administration of TNGIIR(2,10 and 50 mg/kg)for up to four weeks did not reduce the blood pressure of SHR,in contrast to captopril(10 mg/kg,orally),but attenuated the mRNA expression of ACE and AT1 receptor(as did captopril).In contrast,both TNGIIR and captopril enhanced the expression of AT2 receptor mRNA.There was no change in the circulating concentration of angiotensin I,but a slight decrease(about 10%)was seen in the concentration of circulating angiotensin II with TNGIIR and captopril.

天麻钩藤饮联合硫酸镁、拉贝洛尔对妊娠期高血压患者的降压效果及血液流变学的影响评价

【目的】观察天麻钩藤饮联合硫酸镁、拉贝洛尔对妊娠期高血压患者的降压效果及血液流变学的影响。【方法】将90例妊娠期高血压肝阳偏亢型患者随机分为联合组和对照组,每组各45例。对照组给予硫酸镁联合拉贝洛尔治疗,联合组在对照组的基础上加用天麻钩藤饮治疗,疗程为5 d。观察2组患者治疗前后收缩压、舒张压、尿蛋白水平及血液流变学指标的变化情况,比较2组患者的不良妊娠结局、不良反应及满意度情况,并以Logistic回归分析法探讨妊娠期高血压患者不良妊娠结局的影响因素。【结果】(1)降压效果方面,治疗后,2组患者的收缩压、舒张压和尿蛋白水平均较治疗前明显降低(P<0.05),且联合组的降低程度均明显优于对照组(P<0.01)。(2)血液流变学方面,治疗后,2组患者的血浆黏度、全血黏度和红细胞比容均较治疗前明显降低(P<0.05),且联合组的降低程度均明显优于对照组(P<0.05或P<0.01)。(3)不良妊娠结局方面,联合组的不良妊娠结局总发生率为11.11%(5/45),明显低于对照组的33.33%(15/45),差异有统计学意义(P<0.05)。(4)满意度方面,联合组的满意度为97.78%(44/45),明显高于对照组的84.44%(38/45),差异有统计学意义(P<0.05)。(5)不良反应方面,联合组的不良反应总发生率为13.33%(6/45),对照组为8.89%(4/45),组间比较,差异无统计学意义(P>0.05)。(6)影响因素方面,经Logistic回归分析,未使用天麻钩藤饮联合拉贝洛尔、硫酸镁治疗及降压效果不佳均是妊娠期高血压患者不良妊娠结局的独立危险因素(均OR>1,P<0.05)。【结论】天麻钩藤饮联合拉贝洛尔、硫酸镁中西医结合治疗妊娠期高血压患者的降压效果确切,能有效改善血液流变学指标以及不良妊娠结局,提升患者的满意度。

Core-shell lipid-polymeric nanoparticles for enhanced oral bioavailability and antihypertensive efficacy of KY5 peptide

Hypertension is the leading risk factor for death and disability, and hypertensive patients always need long-term oral antihypertensive drugs. Some bioactive peptides that extracted from animals or plants have shown excellent advantages on antihypertension. However, the oral delivery of these peptides is always failure on account of instability and poor absorption in the gastrointestinal tract. Herein, we developed a core-shell lipid-polymeric nanoparticle for oral delivery of a highly efficient antihypertensive peptide KY5(KY5-CSs). KY5-CSs had a particle size of 216.7 ± 2.5 nm, with a narrow PDI of 0.07 ± 0.01.The zeta potential was-4.1 ± 0.1 m V. It exhibited good stability in 4 ℃ and possessed a controlled release behavior in gastrointestinal tract. The cellular uptake study proved that the lipid shell imparted unique capability of permeation across the mucus layer and internalization by Caco-2/HT-29 cells. In addition, KY5-CSs enhanced in situ intestinal absorption in SD rats. The pharmacokinetic studies and antihypertensive efficacy showed a superior oral absorption and antihypertensive effect of KY5-CSs than KY5-NPs. In conclusion, the core-shell lipid-polymeric nanoparticles will provide attractive potential for oral delivery of antihypertensive peptides.

耳穴压豆联合饮食控制疗法对老年高血压患者的作用效果

目的观察耳穴压豆联合饮食控制疗法对老年高血压患者的降压效果。方法便利选取河南省中医院2020年8月至2022年8月收治的老年高血压患者80例进行研究,以平行对照法随机分组,接受常规干预的患者纳入对照组(40例),接受耳穴压豆联合饮食控制疗法的患者纳入试验组(40例)。比较两组治疗总有效率、疾病认知程度、生活质量[简明健康状况调查表(SF-36)]、并发症发生率及治疗依从性。结果试验组治疗总有效率、疾病认知程度评分、SF-36评分、并发症发生率、治疗依从性高于对照组,差异有统计学意义(P<0.05)。结论高血压老年患者实行耳穴压豆联合饮食控制疗法,能够辅助患者维持稳定的血压水平,提升生活质量,正确认知自身疾病,利于预后。

超高效液相色谱-串联质谱法测定调节三高类保健食品中59种非法添加药物

本实验建立了调节三高类保健食品中59种非法添加药物的超高效液相色谱-串联质谱检测方法。样品经甲醇提取,QuEChERS净化,氮吹至近干,1 mL 40%甲醇溶液(体积分数)复溶,以乙腈和0.1%甲酸溶液(5 mmol/L乙酸铵)为流动相,经ACQUITY UPLC HSS T3反相柱梯度分离,超高效液相色谱-串联质谱在正、负离子模式下多反应监测,采用基质外标法定量。结果表明:59种非法添加药物在线性范围内,决定系数(R^(2))均大于0.980,回收率在60.2%~119.5%之间,相对标准偏差在1.2%~15.0%之间。该方法具有前处理较简单、分析时间较短、灵敏度好、准确度高、杂质干扰小等特点,可以用于调节三高类保健食品中多种非法添加药物的检测。

食源性多肽的降血压作用及其机制研究进展

文章总结了食源性降血压肽的作用机制,包括基于RAAS系统的ACE/AngⅡ/AT1R信号通路和ACE2/Ang(1-7)/MasR信号通路,以及以KNOS系统通路为靶点的PI3K/Akt/eNOS信号通路、PPAR-γ/caspase3/MAPK/eNOS信号通路和L型Ca ^(2+)通道。此外,还介绍了近年发现的通过抑制内皮素转换酶(endothelin converting enzyme,ECE)活性降低血压等途径。

Clinical Significance of Evaluating Antihyperten-sive Effect with Arterial Compliance

Objective To evaluate the clinical significance of antihypertensive effect with arterial compliance. Methods In males, 72 cases were control group, 35 cases were EH-controlled, and 35 cases were EH-uncontrolled groups. Blood pressure and arterial compliance (Cl and C2) were detected by HDI DO-2020. Results In the EH-uncontrolled group,the values of systolic blood pressure ( SBP ) , diastolic blood pressure (DBF) , mean arterial pressure (MAP ) , and pulse pressure (PP) were significantly higher than those of the control and the EH-controlled groups (P<0. 01) , however,there was no difference between the control and the EH-controlled groups. In the EH-uncon-trolled group,the values of Cl and C2 were lower than those of both the control and the EH-controlled groups (P<0. 01) ,again,wtih no difference between the control and the EH-controlled groups. Conclusion Arterial compliance (Cl and C2) measurements may serve as a sensitive indicator of evaluating antihypertensive effect.

Effect of morin, a flavonoid against DOCA-salt hypertensive rats:a dose dependent study

Objective:To determine the protective effect of morin, a flavonoid against deoxycorticosterone acetate(DOCA)-salt induced hypertension in male Wistar rats.Methods:Hypertension was induced in uninephrectomized rats by weekly twice subcutaneous injection of DOCA(25 mg/kg bw) and 1% NaCl in the drinking water for six consecutive weeks. Effect of morin against DOCA-salt induced hypertension was evaluated by measuring blood pressure and performing biochemical estimations and histopathological examination of renal tissues.Results:DOCA-salt hypertensive rats showed considerably increased systolic and diastolic blood pressure,serum hepatic marker enzyme activities such as aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) and gamma-glutamyl transpeptidase(GGT)and renal function markers(urea, uric acid and creatinine) in plasma. Oral administration of morin(25, 50 and 75 mg/kg bw) brought back all the above parameters to near normal level.Histopathology of kidney also confirmed the biochemical findings of this study. The effect at a dose of 50 mg/kg bw of morin was more pronounced than that of the other two doses(25 and 75 mg/kg bw).Conclusions:These findings indicate that morin exhibits strong antihypertensive effect against DOCA-salt induced hypertension.

Production of the Blood Pressure Lowing Peptides from Brown Alga(Undaria pinnatifida)

Brown alga (Undaria pinnatifida) was treated with alginate lyase and hydrolyzed using 17 kinds of proteases andthe inhibitory activity of the hydrolysates for the angiotensin-I-converting enzyme (ACE) was measured. Four hydrolysateswith potent ACE-inhibitory activity were administered singly and orally to spontaneously hypertensive rats (SHRs). The sys-tolic blood pressure of SHRs decreases significantly after single oral administration of the brown alga hydrolysates by pro-tease S ’Amano’ (from Bacillus stearothermophilus) at the concentration of 10 (mg protein) (kg body weight)-1. In the 17weeks of feeding experiment, 7-week-old SHRs were fed standard diet supplemented with the brown alga hydrolysates for 10weeks. In SHRs fed 1.0 and 0.1% brown alga hydrolysates, elevating of systolic bloodpressure was significantly suppressedfor 7 weeks. To elucidate the active components, the brown alga hydrolysates were fractionated by 1-butanol extraction andHPLC on a reverse-phase column. Seven kinds of ACE-inhibitory peptides were isolated and identified by amino acid compo-sition analysis, sequence analysis, and LC-MS with the results Val-Tyr, Ile-Tyr, Ala-Trp, Phe-Tyr, Val-Trp, Ile-Trp, andLeu-Trp. Each peptide was determined to have an antihypertensive effect after a single oral administration in SHRs. Thebrown alga hydrolysates were also confirmed to decrease the blood pressure in humans.

Preparation and bioactivity evaluation of low salt peptide from sunf lower seed meal

Sunflower seed meal peptide as one sort of bioactive peptide has intensively application prospects. However, preparation of low salt peptide from sunflower seed meal with high efficiency remains a challenge. In this study, single and compound proteases were optimized to hydrolyze protein. Results showed that hydrolysis at pH 7.0 by proteases resulted in ash content in the range of 5.66%-7.37% and small peptides. Among all hydrolysis processes, sequential hydrolysis of Alcalase with Flavourzyme and Alcalase with Protamex showed higher nitrogen recovery ratio (67.66% and 66.49%, respectively). Furthermore, biological activities of peptides were investigated by testing their ABTS (2,2-azinobis (3-ethylben-zothiazoline-6-sulfonic acid) diammonium salt) radical scavenging activity, DPPH (2,2-diphenyl-1-picrylhydrazil) radical scavenging activity and angiotensin converting enzyme (ACE) inhibitory activity. Peptide hydrolyzed by Alcalase with Papain presented the highest antioxidant activity, followed by Alcalase with Protamex, with ABTS scavenging rate as 63.01% and 31.75%, and DPPH scavenging rate as 56.04% and 28.06%, respectively. Synchronously, peptide hydrolyzed by Alcalase with Protamex and Alcalase with Alcalase had the highest ACE inhibitory activity (56.74%, 56.76%). In conclusion, hydrolysis by proteases Alcalase with Protamex at pH 7.0 was the most effective method for the preparation of low salt peptide from sunflower seed meal, which could be an alternative for anti-oxidants and anti-vasoconstrictor.

Process optimization,texture and microstructure of novel kelp tofu

Laminaria japonica Aresch as an edible and medicine dual-purpose marine algae,has been gradually accepted by people.Tofu was Chinese traditional food,combining kelp function ingredients with tofu has practical value.The extraction-optimization methodology and the sequences of kelp antihypertensive peptide(KAP)were investigated.The sensory,whiteness,water retention ability(WRA)and microstructure of KAP tofu were evaluated.The scanning electron microscope(SEM)results showed KAP addition(20%)significantly improved the tofu texture,with a denser network composed of relatively even pores.Compared with gypsum tofu and glucose-δ-interior fat(GDL)tofu,KAP tofu had significantly higher WRA(94.49±0.49)%and sensory evaluation score value(92.54±0.52),and a significantly lower IC_(50) value at(2.06±0.04)mg/mL(P<0.05).The maximum IC_(50) value(4.14 mg/mL)of kelp enzymatic hydrolysate was observed at enzyme(at an alkaline protease:trypsin ratio of 2:1)concentration 1.5%,temperature 55℃ and time 2 h.The sequences of 8 identified peptides were Lys-Tyr,Phe-Tyr,Gly-Lys-Tyr,Ala-Lys-Tyr,Ser-Lys-Thr-Tyr,Lys-Lys-Phe-Tyr,Lys-Phe-Lys-Tyr and Ala-Lys-Tyr-Ser-Tyr with IC_(50) values of 5.24,4.83,7.94,7.52,20.63,15.33,10.73 and 2.42μmol/L,respectively.These results indicated the potential use of KAP tofu as a valuable resource for development of functional foods.

重组降血压肽ACEIP的表达及活性鉴定

选择降血压肽WQVLPNAVPAK,人工合成大肠杆菌密码子优化后六串联体血管紧张素转换酶抑制肽(angiotensin I-converting enzyme inhibitory peptide,ACEIP)基因片段ACEIP,将其克隆至表达载体pET30a后构建重组质粒pET30a-ACEIP。该重组质粒经限制性内切酶Nde I和HindIII双酶切鉴定、菌落聚合酶链式反应鉴定后,将其化转至大肠杆菌BL21(DE3)感受态细胞中,构建了表达工程菌大肠杆菌BL21(DE3)/pET30a-ACEIP。工程菌经终浓度为0.8 mmol/L异丙基-β-D-硫代半乳糖苷导后,Tricine-十二烷基硫酸钠-聚丙烯酰胺凝胶电泳显示在分子质量约为8.7 kDa处出现一条明显条带。经Ni^(2+)亲和层析、肠激酶酶切后纯化得到串联多肽ACEIP。其中融合蛋白的表达量为61.30 mg/L,串联多肽ACEIP的表达量为57.84 mg/L。串联多肽经胰蛋白酶酶解后的IC_(50)值为6.39 mg/m L,ACE抑制活性高于单体肽WQVLPNAVPAK的抑制活性(IC_(50)为12.34 mg/mL)。

牛蒡根蛋白-降压肽纳米颗粒的制备及稳定性表征

该研究采用缓冲液浸提法提取牛蒡根蛋白(Burdock Root Protein,BRP),并制备载泥鳅降压肽丙氨酸-组氨酸-亮氨酸-亮氨酸(Ala-His-Leu-Leu,AHLL)的牛蒡根蛋白纳米颗粒(Burdock Root Protein Nanoparticles Loaded with Loach Antihypertensive Peptide,BANPs)。BRP与AHLL通过自组装形成BANPs,采用扫描电镜、荧光与紫外-可见光光谱扫描、傅里叶红外光谱等对BANPs的结构和分子间相互作用进行表征,考察了不同温度、pH值对BANPs稳定性的影响。结果发现,pH值5.0时,BANPs粒径较小(231.47 nm),带负电荷(-19.10 mV),BRP分子通过静电相互作用和疏水相互作用与AHLL分子结合。随着BRP与AHLL质量浓度的增加,当BRP为8 mg/mL,AHLL为200μg/mL时,BRP对AHLL的包封率提高到77.28%,载药量提高到23.90%。在60~100℃范围内,BANPs的温度稳定性较高,与游离AHLL相比降解率低至46.90%;在pH值4.0~8.0范围内BANPs的pH稳定性较高,与游离AHLL相比降解率低至33.16%。该研究表明,BRP纳米载体可以有效地保护AHLL免受pH值和热降解的影响,具有作为功能性食品中生物活性肽的纳米递送系统的潜力。

乳源性血管紧张素转换酶抑制肽的研究进展

高血压是威胁人类健康的“无声杀手”,乳源性ACE抑制肽是以乳类蛋白为原料经过酶解或发酵制备的具有降血压作用的肽。近年来,乳源性ACE抑制肽被认为是一种天然且相对安全的生物活性肽,因为具有生物活性高、毒性低、易代谢和良好的降压效果等特点而受到人们日益关注,并逐渐被应用到保健品、功能性食品等领域。本文综述了乳源性ACE抑制肽的来源(包括化学方法合成与天然食品来源)、制备方法(包括体外酶解与微生物发酵)。归纳总结了乳源ACE抑制肽的分离纯化及构效关系等方面的研究进展并简介在食品与临床方面的应用及未来发展前景,以期为推动我国开发ACE抑制肽有关产品提供参考。

发芽青稞的营养品质及降血压效果

作者以发芽前后青稞中β-葡聚糖、γ-氨基丁酸、游离氨基酸、总多酚等营养成分的质量分数以及β-葡聚糖酶、蛋白酶等酶活性为指标,并结合高血压大鼠收缩压、心率等指标的变化情况,研究萌发对青稞营养品质和其降血压效果的影响。结果发现,青稞β-葡聚糖、淀粉和蛋白质质量分数随萌发时间延长而降低,γ-氨基丁酸质量分数在萌发48 h达到最高,总多酚、总黄酮质量分数以及β-葡聚糖酶、淀粉酶和蛋白酶的活力随萌发时间延长而增加。总游离氨基酸质量分数尤其是必需氨基酸质量分数经萌发处理后显著升高(P<0.05),表明发芽能提高青稞营养价值。此外,与青稞相比,发芽青稞更利于降低高血压大鼠的收缩压、心率、血管紧张素Ⅱ和血管生成素(P<0.05),表明发芽青稞有更好的缓解高血压作用。