Angiotensin-converting enzyme

血管紧张素转换酶
  • 文章类型: Journal Article
    本研究研究了厌氧处理对紫色叶茶非挥发性成分和血管紧张素转换酶(ACE)抑制活性的影响。结果表明,经过8小时的厌氧处理,γ-氨基丁酸(GABA)含量从0.02mg/g显著增加到1.72mg/g(p<0.05),而乳酸含量从检测不到的水平逐渐上升到3.56mg/g。值得注意的是,某些黄酮醇如槲皮素和杨梅素表现出显著的增量,而花色苷(1.01mg/g)和表没食子儿茶素-3-(3\'\'-O-甲基)没食子酸酯(13.47mg/g)的总含量几乎没有变化。此外,在浓度为2mg/mL时,紫色叶茶的ACE抑制率从42.16%显著提高到49.20%(p<0.05)。此外,在体外ACE抑制活性和分子对接分析中,galloted儿茶素比非galloted儿茶素均显示出较强的ACE抑制活性。这些发现可能有助于开发具有潜在治疗高血压的特殊紫色叶茶产品。
    This study investigated the effect of anaerobic treatment on the non-volatile components and angiotensin-converting enzyme (ACE) inhibitory activity in purple-colored leaf tea. Results showed that after 8 h of anaerobic treatment, the γ-aminobutyric acid (GABA) content significantly increased from 0.02 mg/g to 1.72 mg/g (p < 0.05), while lactic acid content gradually rose from non-detectable levels to 3.56 mg/g. Notably, certain flavonols like quercetin and myricetin exhibited significant increments, whereas the total anthocyanins (1.01 mg/g) and epigallocatechin-3-(3\'\'-O-methyl) gallate (13.47 mg/g) contents remained almost unchanged. Furthermore, the ACE inhibition rate of purple-colored leaf tea increased significantly from 42.16% to 49.20% (p < 0.05) at a concentration of 2 mg/mL. Moreover, galloylated catechins showed stronger ACE inhibitory activity than non-galloylated catechins in both in vitro ACE inhibitory activity and molecular docking analysis. These findings might contribute to the development of special purple-colored leaf tea products with potential therapy for hypertension.
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  • 文章类型: Journal Article
    异亮氨酸-脯氨酸-脯氨酸(Ile-Pro-Pro,IPP)是抑制血管紧张素转换酶(ACE)活性的天然食物源三肽。这项研究的目的是确定IPP在减弱交感神经活动中的中枢和外周作用。氧化应激和高血压。雄性Sprague-Dawley大鼠接受假手术(Sham)或两肾一夹(2K1C)手术,以诱发肾血管性高血压。记录肾交感神经活动和血压。向下丘脑室旁核(PVN)双侧微量注射IPP减弱了交感神经活动(-16.1±2.5%,P<0.001)和高血压(-8.7±1.5mmHg,P<0.01)在2K1C大鼠中通过抑制ACE活性以及随后的血管紧张素II和PVN中的超氧化物产生。静脉内注射IPP也减弱了交感神经活动(-15.1±2.1%,P<0.001)和高血压(-16.8±2.3mmHg,P<0.001)通过抑制2K1C大鼠PVN和动脉的ACE活性和氧化应激。静脉内IPP的作用持续时间比PVN微量注射的作用持续时间长,但是静脉注射的交感神经抑制作用比PVN微量注射晚。腹膜内注射IPP(400pmol/天,持续20天)可通过抑制2K1C大鼠PVN和动脉的ACE活性和氧化应激来减轻高血压和血管重塑。这些结果表明IPP通过抑制ACE活性和氧化应激来减弱高血压和交感神经活性。外周IPP的交感神经抑制作用主要是由ACE抑制PVN引起的,降压作用与交感神经抑制和动脉ACE抑制有关。长期腹膜内IPP治疗减轻高血压,氧化应激和血管重塑。
    Isoleucine-proline-proline (Ile-Pro-Pro, IPP) is a natural food source tripeptide that inhibits angiotensin-converting enzyme (ACE) activity. The aim of this study was to determine the central and peripheral roles of IPP in attenuating sympathetic activity, oxidative stress and hypertension. Male Sprague-Dawley rats were subjected to sham-operated surgery (Sham) or two-kidney one-clip (2K1C) surgery to induce renovascular hypertension. Renal sympathetic nerve activity and blood pressure were recorded. Bilateral microinjections of IPP to hypothalamic paraventricular nucleus (PVN) attenuated sympathetic activity (-16.1 ± 2.5%, P < 0.001) and hypertension (-8.7 ± 1.5 mmHg, P < 0.01) in 2K1C rats by inhibiting ACE activity and subsequent angiotensin II and superoxide production in the PVN. Intravenous injections of IPP also attenuated sympathetic activity (-15.1 ± 2.1%, P < 0.001) and hypertension (-16.8 ± 2.3 mmHg, P < 0.001) via inhibiting ACE activity and oxidative stress in both PVN and arteries of 2K1C rats. The duration of the effects of the intravenous IPP was longer than those of the PVN microinjection, but the sympatho-inhibitory effect of intravenous injections occurred later than that of the PVN microinjection. Intraperitoneal injection of IPP (400 pmol/day for 20 days) attenuated hypertension and vascular remodeling via inhibiting ACE activity and oxidative stress in both PVN and arteries of 2K1C rats. These results indicate that IPP attenuates hypertension and sympathetic activity by inhibiting ACE activity and oxidative stress. The sympathoinhibitory effect of peripheral IPP is mainly caused by the ACE inhibition in PVN, and the antihypertensive effect is related to the sympathoinhibition and the arterial ACE inhibition. Long-term intraperitoneal IPP therapy attenuates hypertension, oxidative stress and vascular remodeling.
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  • 文章类型: Journal Article
    炎症性肠病(IBD)是一种由肠中的免疫疾病引起的非特异性慢性炎症性疾病,易于复发和无法治愈。对IBD发病机制的认识尚不清楚。在这项研究中,我们发现ACE(血管紧张素转换酶),在肠道中大量表达,在IBD中发挥着重要作用。斑马鱼中ACE的缺失引起肠道炎症,炎症标记基因白细胞介素1β(il1b)表达增加,基质金属肽酶9(mmp9),骨髓特异性过氧化物酶(mpx),白细胞衍生的趋化因子-2-样(凝集素2l),和趋化因子(C-X-C基序)配体8b(cxcl8b)。此外,e-/-突变体的粘液分泌明显高于野生型斑马鱼,验证肠道炎症的表型。使用葡聚糖硫酸钠(DSS)构建的IBD模型进一步证实了这一点,其中突变斑马鱼对肠炎的易感性更高。我们的研究揭示了ACE在肠道稳态中的作用,为潜在的治疗干预提供了新的目标。
    Inflammatory bowel disease (IBD) is a nonspecific chronic inflammatory disease resulting from an immune disorder in the intestine that is prone to relapse and incurable. The understanding of the pathogenesis of IBD remains unclear. In this study, we found that ace (angiotensin-converting enzyme), expressed abundantly in the intestine, plays an important role in IBD. The deletion of ace in zebrafish caused intestinal inflammation with increased expression of the inflammatory marker genes interleukin 1 beta (il1b), matrix metallopeptidase 9 (mmp9), myeloid-specific peroxidase (mpx), leukocyte cell-derived chemotaxin-2-like (lect2l), and chemokine (C-X-C motif) ligand 8b (cxcl8b). Moreover, the secretion of mucus in the ace-/- mutants was significantly higher than that in the wild-type zebrafish, validating the phenotype of intestinal inflammation. This was further confirmed by the IBD model constructed using dextran sodium sulfate (DSS), in which the mutant zebrafish had a higher susceptibility to enteritis. Our study reveals the role of ace in intestinal homeostasis, providing a new target for potential therapeutic interventions.
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  • 文章类型: Journal Article
    血管紧张素转换酶(ACE)与心脏代谢危险因素和动脉粥样硬化密切相关。本研究旨在探讨ACE基因的插入/缺失(I/D)变异是否影响心脏代谢危险因素。早发冠状动脉疾病(PCAD),和冠状动脉病变的严重程度。PubMed,科克伦图书馆,中央,CINAHL,和ClinicalTrials.gov被搜索到2023年12月22日。94,270人被纳入分析。DD基因型的携带者有较高的甘油三酯(TG)水平,总胆固醇(TC),低密度脂蛋白胆固醇(LDL-C),收缩压(SBP),舒张压(DBP),体重指数(BMI),和腰围(WC)比II或ID基因型的携带者。此外,DD基因型携带者是PCAD和多血管病变的高危人群。ACEI/D变体对血脂水平的影响在美国个体中显着,但在男性个体中则更强。相比之下,ACEI/D变体对PCAD和冠状动脉病变严重程度的影响在白种人个体中主要显著.这项研究表明,ACEI/D变体对心脏代谢危险因素有轻微但显著的影响,PCAD,和冠状动脉病变的严重程度。血管紧张素转换酶抑制剂(ACEI)可能使ACEDD基因型的高危人群受益,以预防PCAD和多血管病变。PROSPERO注册号:CRD42023426732。
    Angiotensin-converting enzyme (ACE) is closely related to cardiometabolic risk factors and atherosclerosis. This study aims to investigate whether the insertion/deletion (I/D) variant of ACE gene impacts cardiometabolic risk factors, premature coronary artery disease (PCAD), and severity of coronary lesions. PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until December 22, 2023. 94,270 individuals were included for the analysis. Carriers of DD genotype had higher levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and waist circumference (WC) than carriers of II or ID genotypes. In addition, carriers of DD genotype were at high risk of PCAD and multiple vessel lesions. The impacts of ACE I/D variant on lipid levels were significant in American individuals but stronger in male individuals. In contrast, the impacts of ACE I/D variant on PCAD and severity of coronary lesions were primarily significant in Caucasian individuals. This study indicates that the ACE I/D variant has a slight but significant impact on cardiometabolic risk factors, PCAD, and severity of coronary lesions. Angiotensin-converting enzyme inhibitors (ACEI) may benefit high-risk populations with ACE DD genotype to prevent PCAD and multiple vessel lesions.PROSPERO registration number: CRD42023426732.
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  • 文章类型: Journal Article
    血管紧张素转换酶(ACE),由N域和C域组成,是血压的关键调节器。使用cACE特异性抑制剂有助于使临床应用中的副作用最小化。豆类是含有ACE抑制肽的蛋白质的良好来源;然而,没有研究报道从豆科中鉴定出cACE特异性抑制肽。在这项研究中,来自种子的热水解产物,豆芽,豆荚,幼苗,和豆科植物的花进行了分析。豆科植物的花朵在大鼠中表现出C域优先ACE抑制和抗高血压作用。筛选豆科植物肽库,鉴定出一种新型的cACE抑制肽,SJ-1.本研究首次从豆科食品中鉴定出cACE抑制肽。SJ-1,从豆科植物的花朵中鉴定出来,与cACE活性位点残基相互作用,导致ACE活性的抑制,缓激肽水平下调,和降低血压。这些发现还表明豆类蛋白质作为cACE抑制肽来源的潜力。
    Angiotensin-converting enzyme (ACE), consisting of N-domain and C-domain, is a key regulator of blood pressure. The use of cACE-specific inhibitors helps minimize side effects in clinical applications. Legumes are a good source of proteins containing ACE inhibitory peptides; however, no studies have reported the identification of cACE-specific inhibitory peptides from Fabaceae. In this study, thermal hydrolysates from seeds, sprouts, pods, seedlings, and flowers of legumes were analyzed. Flowers of legumes exhibited a C-domain-preference ACE inhibition and anti-hypertensive effect in rats. Screening the legume peptide library identified a novel cACE inhibitory peptide, SJ-1. This study reported the first identification of cACE inhibitory peptide from Fabaceae foods. SJ-1, identified from the legume flowers, interacted with active site residues of cACE, leading to the inhibition of ACE activity, downregulation of bradykinin levels, and reduction of blood pressure. These findings also suggested the potential of legume proteins as a source of cACE inhibitory peptides.
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  • 文章类型: Journal Article
    低分子量食物衍生肽,高生物利用度,良好的吸收性已被用作血管紧张素转换酶(ACE)抑制剂。在本研究中,花生肽的体外抑制动力学,在硅片筛选中,ACE抑制活性的验证,分子动力学(MD)模拟,和HUVEC细胞进行系统鉴定ACE与花生肽相互作用的抑制机制。结果表明,FPHPP,FPHY,和FPHFD肽具有良好的热,pH值,和消化稳定性。MD轨迹阐明了肽和ACE之间的动态相关性,并验证了特异性结合相互作用。值得注意的是,FPHPP是最好的抑制剂,具有最强的结合亲和力,并显着增加NO,SOD生产,和AT2R表达式,并减少ROS,MDA,ET-1级,ACE,和AT1R在AngII损伤的HUVEC细胞中的积累。
    Food-derived peptides with low molecular weight, high bioavailability, and good absorptivity have been exploited as angiotensin-converting enzyme (ACE) inhibitors. In the present study, in-vitro inhibition kinetics of peanut peptides, in silico screening, validation of ACE inhibitory activity, molecular dynamics (MD) simulations, and HUVEC cells were performed to systematically identify the inhibitory mechanism of ACE interacting with peanut peptides. The results indicate that FPHPP, FPHY, and FPHFD peptides have good thermal, pH, and digestive stability. MD trajectories elucidate the dynamic correlation between peptides and ACE and verify the specific binding interaction. Noteworthily, FPHPP is the best inhibitor with a strongest binding affinity and significantly increases NO, SOD production, and AT2R expression, and decreases ROS, MDA, ET-1 levels, ACE, and AT1R accumulation in Ang II-injury HUVEC cells.
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  • 文章类型: Journal Article
    急性胰腺炎是由各种损伤形式(胆结石,高甘油三酯,酒精,等。).病毒性胰腺炎是一种临床罕见的疾病类型,易被临床医生忽视,造成严重的不良后果。病毒性胰腺炎涉及病毒进入胰腺细胞,引发炎症,免疫反应激活,和酶自动消化,导致组织损伤和潜在的并发症。目前,关于病毒性胰腺炎的报道很少,其中大部分是病例报告。这篇综述通过描述病毒性胰腺炎的发病率来提高临床医生的认识和患者的护理。
    Acute pancreatitis is caused by trypsinogen activation in acinar cells caused by various injury forms (gallstone, high triglycerides, alcohol, etc.). Viral pancreatitis is a clinically rare disease type, which is easily neglected by clinicians and causes serious adverse consequences. Viral pancreatitis involves the entry of viruses into pancreatic cells, triggering inflammation, immune response activation, and enzymatic autodigestion, leading to tissue damage and potential complications. At present, there are few available reports on viral pancreatitis, most of which are case reports. This review brings attention to clinicians by describing the incidence of viral pancreatitis to enhance clinical understanding and patient care.
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  • 文章类型: Journal Article
    背景:高血压是全球最常见的慢性严重健康问题。玉米丝(CS),玉米(ZeamaysL.)的柔滑纤维,作为治疗水肿和高血压的传统用法历史悠久。
    目的:本研究的目的是探索CS发挥其抗高血压作用的潜在机制,并研究CS水提物中生物活性分子的存在。
    方法:我们分析了CS沸水提取物对血管紧张素转换酶(ACE)活性的影响,调节血压的关键酶。使用蛋白质组学和生物信息学工具鉴定来自CS提取物的ACE抑制肽。通过氢-氘交换质谱(HDX-MS)确定这些肽与ACE之间的结合界面。随后,在自发性高血压大鼠(SHR)中进一步研究了肽的抗高血压作用。
    结果:我们的数据显示CS提取物显示出ACE活性的剂量依赖性抑制。液相色谱-串联质谱法鉴定了CS沸水提取物中具有1313种不同肽片段的热稳定肽库。其中,通过PeptideRanker和BIOPEP-UWM分析选择CS-1(LVPGWTKPICIGR)。体外ACE抑制试验证实CS-1表现出剂量依赖性ACE抑制,IC50值为10.32±0.41μmol/L(使用HHL作为底物)和13.74±1.87μmol/L(使用ZFHL作为底物)。口服CS-1导致血压显著的剂量依赖性降低,摄入后0.5小时发生最大下降(42.33±13.08mmHg)。HDX-MS分析显示CS-1与ACE的锌结合基序相互作用,预测了CS-1与特定残基之间的氢键相互作用,包括N域中的His361,以及ACEC域中的His382、Gly386和His387。这些发现表明CS-1与ACE的锌结合基序中的残基的相互作用导致ACE活性抑制和随后的大鼠血压降低。
    结论:一种新型热稳定ACE抑制肽,与ACE的锌结合基序相互作用并降低SHR的血压,在CS提取物中鉴定。CS提取物中ACE抑制肽的存在支持了其在高血压的民族药理学中的传统用途。
    BACKGROUND: Hypertension is the most common and chronic severe health problem globally. Corn silk (CS), the silky fibers of corn (Zea mays L.), has a long history of traditional usage as a remedy for edema and hypertension.
    OBJECTIVE: The aim of the study was to explore the underlying mechanism by which CS exerts its anti-hypertensive effects and investigate the presence of bioactive molecules in CS aqueous extract.
    METHODS: We analyzed the effects of boiling water extract of CS on angiotensin-converting enzyme (ACE) activities, the critical enzyme involved in the regulation of blood pressure. ACE inhibitory peptides from CS extract were identified using proteomics and bioinformatics tools. The binding interfaces between these peptides and ACE were defined by hydrogen-deuterium exchange mass spectrometry (HDX-MS). Subsequently, the anti-hypertensive effects of peptides were further investigated in spontaneously hypertensive rats (SHR).
    RESULTS: Our data showed that CS extract exhibited dose-dependent inhibition of ACE activity. Liquid chromatography-tandem mass spectrometry identified a heat-stable peptide bank with 1313 distinct peptide fragments within the CS boiling water extract. Among these, CS-1 (LVPGWTKPICIGR) was selected through PeptideRanker and BIOPEP-UWM analyses. In vitro ACE inhibitory assays confirmed that CS-1 exhibited dose-dependent ACE inhibition, with IC50 values of 10.32 ± 0.41 μmol/L (using HHL as the substrate) and 13.74 ± 1.87 μmol/L (using ZFHL as the substrate). Oral administration of CS-1 led to a significant dose-dependent reduction in blood pressure, with the maximal decrease (42.33 ± 13.08 mmHg) occurring 0.5 h after ingestion. HDX-MS analysis revealed that CS-1 interacted with the zinc-binding motif of ACE, and hydrogen bond interactions were predicted between CS-1 and specific residues, including His361 in the N-domain, as well as His382, Gly386, and His387 in the C-domain of ACE. These findings suggested that the interaction of CS-1 with the residues in the zinc-binding motif of ACE led to ACE activity inhibition and a subsequent decrease in blood pressure in rats.
    CONCLUSIONS: A novel heat-stable ACE inhibitory peptide, which interacted with the zinc-binding motif of ACE and reduced blood pressure in SHR, was identified in the CS extract. The presence of ACE inhibitory peptides in the CS extract supports its traditional use in ethnopharmacology for hypertension.
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  • 文章类型: Journal Article
    血管紧张素转换酶(ACE)活性的有效和快速检测对于预防高血压和发现新的血管紧张素转换酶抑制剂(ACEI)很重要。在这项工作中,制备了单激发和双发射生物质衍生碳量子点(CQDs),并将其用于ACE的比率荧光检测。新鲜榕叶用乙醇和丙酮提取,以提取液为前驱体制备具有单激发和双发射特性的碳量子点(BL-CQDs)。合成的BL-CQDs约为1.7nm,具有类似石墨烯的结构,表面含有多种亲水官能团,并具有良好的荧光性能。其荧光强度比(I677/I460)与ACE活性在0.02-0.8Ul-1范围内呈线性关系。回归方程为△F=2.5371CACE-0.0311。该方法成功应用于猪肺和人血清中ACE活性的测定,并研究了黄酮类提取物和卡托普利片对ACE活性的抑制作用,可用于ACEI的筛查。Bel-7404细胞在高浓度BL-CQDs条件下的存活率和荧光成像显示BL-CQDs具有较低的细胞毒性和较好的生物相容性。这些结果表明BL-CQDs可以作为一种优良的荧光探针,为筛选ACE活性和植物来源的ACEI提供了新的方法。
    Efficient and rapid detection of angiotensin-converting enzyme (ACE) activity is important for preventing hypertension and the discovery of new angiotensin-converting enzyme inhibitors (ACEI). In this work, a single-excitation and double-emission biomass-derived carbon quantum dots (CQDs) was prepared and applied for ratiometric fluorescence detection of ACE. Fresh banyan leaves were extracted with ethanol and acetone, and the extracted solution was used as the precursor to produce the carbon quantum dots (BL-CQDs) with single-excitation and double-emission properties. The synthesized BL-CQDs is about 1.7 nm, has a graphene-like structure, contains a variety of hydrophilic functional groups on the surface, and has good fluorescence properties. Its fluorescence intensity ratio (I677/I460) is linear with ACE activity in the range of 0.02-0.8 U l-1. The regression equation is△F=2.5371CACE-0.0311. The method was successfully applied to the determination of ACE activity in pig lung and human serum, and the inhibitory efficiency of the flavonoid extract and captopril tablets on ACE activity was also investigated, which can be applied to the screening of ACEI. The survival rate and fluorescence imaging of Bel-7404 cells under the condition of high concentration BL-CQDs showed BL-CQDs had low cytotoxicity and good biocompatibility. These results indicate that the BL-CQDs can be used as an excellent fluorescent probe, providing a new method for screening ACE activity and plant-derived ACEI.
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  • 文章类型: Journal Article
    乳酸菌(LAB),一种广泛用于功能性食品的微生物,近年来获得了重要的研究关注。某些菌株具有蛋白水解能力,从乳制品蛋白中释放潜在的抗高血压肽,这促使我们从一种未经研究的独特成分中探索LAB菌株,大曲。我们用钙溶解环法从传统大曲中筛选出67株LAB菌株。选择表现出超过50%的ACE抑制(ACE-I)活性的16个菌株用于16SrDNA测序和安全性评估。值得注意的是,屎肠球菌CP640和鼠李糖乳杆菌CP658表现出显著的ACE-I活性,这是菌株在重组脱脂乳中发酵的结果。这2个菌株没有表现出溶血活性或抗生素抗性。它们也不产生生物胺,并且在胃肠道中显示出高存活率。此外,与SHR的阴性对照相比,屎肠球菌CP640和鼠李糖乳杆菌CP658发酵乳中自发性高血压大鼠(SHR)的血压水平显着降低。重要的是,在正常Wistar-Kyoto大鼠(WKY大鼠)中未观察到不良反应。通过生理分析,血清,和尿液相关指标,观察到屎肠球菌CP640和鼠李糖乳杆菌CP658具有促进SHR体重增加的潜力,缓解过度的心率,改善肾功能指标,并有效调节SHR的血糖和尿酸水平。这两种菌株在降低血压方面表现出最佳特性,并且将来有可能用于功能性乳制品。
    Lactic acid bacteria (LAB), a type of microorganism widely used in functional foods, has gained notable research attention in recent years. Certain strains possess the proteolytic ability to release potentially antihypertensive peptides from dairy proteins, which prompted us to explore the LAB strains from an understudied and unique ingredient, Daqu. We screened for 67 strains of LAB strains from traditional Daqu using the calcium dissolution ring method. Sixteen strains exhibiting angiotensin-converting enzyme inhibition (ACE-I) activity exceeding 50% were chosen for 16S rDNA sequencing and safety assessment. It is noteworthy that Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 exhibited significant ACE-I activity, which was the result of strain fermentation in reconstituted skim milk. These 2 strains did not exhibit hemolytic activity or antibiotic resistance. They also did not produce biogenic amines and showed high survival rates in the gastrointestinal tract. Additionally, Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 fermented milk exhibited a notable reduction in blood pressure levels in spontaneously hypertensive rats (SHR) compared with negative controls in SHR. Importantly, no adverse effect was observed in normal Wistar-Kyoto rats. Through the analysis of physiological, serum, and urine-related indicators, it was observed that Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 have the potential to promote weight gain in SHR, alleviate excessive heart rate, improve renal function indicators, and effectively regulate blood sugar and uric acid levels in SHR. These 2 strains showed optimal properties in lowering blood pressure and have the potential to be used in functional dairy products in the future.
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