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angiotensin-converting enzyme inhibitors from plants: A review of their diversity, modes of action, prospects, and concerns in the management of diabetes-centric complications

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Journal of Integrative Medicine 2021年第6期19卷 478-492页

作者： Rakhi Chakraborty Swarnendu Roy Department of Botany A.P.C.Roy Government CollegeMatigara 734010West BengalIndia Plant Biochemistry Laboratory Department of BotanyUniversity of North BengalRaja Rammohunpur 734011West BengalIndia

angiotensin-converting enzyme(ACE)inhibitors are antihypertensive medications often used in the treatment of diabetes-related *** ACE inhibitors are known to cause serious side effects like hypotension,renal insufficiency,and ***,there has been an intensifying search for natural ACE *** plants or plant-based extracts are known to possess ACEinhibitory *** this review,articles focusing on the natural ACE inhibitors extracted from plants were retrieved from databases like Google Scholar,Pub Med,Scopus,and Web of *** have found more than 50 plant species with ACE-inhibitory *** them,Angelica keiskei,Momordica charantia,Muntingia calabura,Prunus domestica,and Peperomia pellucida were the most potent,showing comparatively lower half-maximal inhibitory concentration *** the bioactive metabolites,peptides(e.g.,Tyr-Glu-Pro,Met-Arg-Trp,and Gln-Phe-Tyr-Ala-Val),phenolics(e.g.,cyanidin-3-Osambubioside and delphinidin-3-O-sambubioside),flavonoids([-]-epicatechin,astilbin,and eupatorin),terpenoids(ursolic acid and oleanolic acid)and alkaloids(berberine and harmaline)isolated from several plant and fungus species were found to possess significant ACE-inhibitory *** were also known to possess promising antioxidant,antidiabetic,antihyperlipidemic and anti-inflammatory *** the minimal side effects and lower toxicity of herbal compounds,development of antihypertensive drugs from these plant extracts or phytocompounds for the treatment of diabetesassociated complications is an important *** review,therefore,focuses on the ACE inhibitors extracted from different plant sources,their possible mechanisms of action,present status,and any safety concerns.

关键词： angiotensin-converting enzyme Inhibitor Herbal medicine Hyperglycaemia Hypertension Bioactive metabolite

Human sperm testicular angiotensin-converting enzyme helps determine human embryo quality

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Asian Journal of Andrology 2018年第5期20卷 498-504页

作者： Marta Gianzo Itziar Urizar-Arenaza Iraia Munoa-Hoyos Zaloa Larreategui Nicolas Garrido Luis Casis Jon Irazusta Nerea Subiran Department of Physiology Faculty of Medicine and Nursery University of the Basque Country (UPV/EHU) Leioa Biscay 48940 Spain In Vitro Fertilization Laboratory IVI Bilbao Landabarri Promenade 1 Leioa Biscay 48940 Spain IVI Foundation IVI Valencia Local Police Square 3 Valencia 46015 Spain

angiotensin-converting enzyme functions in the male reproductive system, but the extent of its function in reproduction is not fully understood. The primary objective of this work was to investigate the relationship between the testicular isoform of angiotensin-converting enzyme present in human spermatozoa and semen parameters, human embryo quality, and assisted reproduction success. A total of 81 semen samples and 635 embryos from couples undergoing oocyte donation cycles at the IVI Bilbao Clinic were analyzed. Semen parameters, embryos quality, and blastocyst development were examined according to the World Health Organization standards and the Spanish Association of Reproduction Biology Studies criteria. The percentage of testicular angiotensin-converting enzyme-positive spermatozoa and the number of molecules per spermatozoon were analyzed by flow cytometry. Both parameters were inversely correlated with human sperm motility. Higher percentages of testicular angiotensin-converting enzyme-positive spermatozoa together with fewer enzyme molecules per spermatozoon were positively correlated with better embryo quality and development. Our results suggest that embryos with a higher implantation potential come from semen samples with higher percentages of testicular angiotensin-converting enzyme-positive cells and fewer enzyme molecules per spermatozoon. Based on these findings, we propose that testicular angiotensin-converting enzyme could be used to aid embryologists in selecting better semen samples for obtaining high-quality blastocysts during in vitro fertilization procedures.

关键词： angiotensin-converting enzyme ART embryonic development human sperm male fertility

Increasing angiotensin-converting enzyme(ACE)2/ACE axes ratio alleviates early pulmonary vascular remodeling in a porcine model of acute pulmonary embolism with cardiac arrest

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World Journal of Emergency Medicine 2022年第3期13卷 208-214页

作者： Hong-li Xiao Lian-xing Zhao Jun Yang Nan Tong Le An Guo-xing Wang Miao-rong Xie Chun-sheng Li Department of Emergency Medicine Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Emergency Internal Medicine the Affiliated Hospital of Qingdao UniversityQingdao 266000China Department of Emergency Medicine Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100050China

BACKGROUND:Acute pulmonary embolism(APE)with cardiac arrest(CA)is characterized by high mortality in emergency due to pulmonary arterial hypertension(PAH).This study aims to determine whether early pulmonary artery remodeling occurs in PAH caused by massive APE with CA and the protective effects of increasing angiotensin-converting enzyme(ACE)2-angiotensin(Ang)(1-7)-Mas receptor axis and ACE-Ang II-Ang II type 1 receptor(AT1)axis(ACE2/ACE axes)ratio on pulmonary artery lesion after return of spontaneous circulation(ROSC).METHODS:To establish a porcine massive APE with CA model,autologous thrombus was injected into the external jugular vein until mean arterial pressure dropped below 30 mmHg(1 mmHg=0.133 kPa).Cardiopulmonary resuscitation and thrombolysis were delivered to regain spontaneous *** were divided into four groups of five pigs each:control group,APE-CA group,ROSC-saline group,and ROSC-captopril group,to examine the endothelial pathological changes and expression of ACE2/ACE axes in pulmonary artery with or without ***:Histological analysis of samples from the APE-CA and ROSC-saline groups showed that pulmonary arterioles were almost completely occluded by accumulated endothelial *** blotting analysis revealed a decrease in the pulmonary arterial ACE2/ACE axes ratio and increases in angiopoietin-2/angiopoietin-1 ratio and expression of vascular endothelial growth factor(VEGF)in the APE-CA group compared with the control *** significantly suppressed the activation of angiopoietin-2/angiopoietin-1 and VEGF in plexiform lesions formed by proliferative endothelial cells after *** also alleviated endothelial cell apoptosis by increasing the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X(Bax)ratio and decreasing cleaved caspase-3 ***:Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC i

关键词： Acute pulmonary embolism Cardiac arrest Early pulmonary vascular remodeling angiotensin-converting enzyme

Altered angiotensin-converting enzyme and its effects on the brain in a rat model of Alzheimer disease

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Chinese Medical Journal 2008年第22期121卷 2320-2323页

作者： HOU De-ren WANG Yan ZHOU Lin CHEN Kun TIAN Yi SONG Zhi BAO Juan YANG Qi-dong Department of Neurology Third Xiangya Hospital Central South University Changsha Hunan 410013 China Department of Neurology First Xiangya Hospital Central South University Changsha Hunan 410013 China

Background Alzheimer disease （AD） is a neurodegenerative disease related to aging. At present, its pathological mechanisms remain unclear. Family members of the renin-angiotensin system （RAS） play a role in neuronal plasticity, as well as formation of learning and memory. In this study, we explore the effects of altered angiotensin-converting enzyme （ACE）, and investigate the possible mechanisms of perindopril, an ACE inhibitor, on brain structure and function in a rat model of AD, as well as the role that ACE plays in AD. Methods Sixty Sprague-Dawley rats were selected and randomly divided into 3 groups： control, AD, and perindopril. Each group consisted of 20 rats, with 10 rats for determining pathology, and the remaining 10 rats for quantifying ACE activity. The rat AD model was established by stereotactically injecting amyloid beta protein （A-beta） 1-42 into the right hippocampus. Learning and memory functions were tested using the Y-type electric maze. The number and morphology of abnormal neurons were determined by haematoxylin and eosin staining. Amyloid deposition was measured by Congo red staining. Finally, ACE activity was estimated by spectrophotometry. Results Compared with the control group, the number of times needed to escape electrical stimuli increased （23.70±3.13, P 〈0.001）, the number of normal neurons in the CA1 region was reduced （density of 96.5±32.6/mm, P 〈0.001）, amyloid deposition was obvious, and ACE activity increased （（34.4±6.6） ***-1, P 〈0.001） in the AD group. In the perindopril group, the number of times needed to escape electrical stimuli decreased （18.50±3.66, P 〈0.001）, the number of abnormal neurons increased （density of CA1 neurons was 180.8±28.5/mm, P 〈0.001）, amyloid deposition was reduced, and ACE activity was down-regulated （（26.2±6.2） ***-1, P 〈0.001）. Conclusions ACE activity increased in the brains of AD rats. Perindopril improved learning and memory in AD rats, which correlated with decreased ACE activity

关键词： Alzheimer disease amyloid beta-protein angiotensin-converting enzyme perindopril

Is the role of the angiotensin-converting enzyme gene in Alzheimer's disease independent of hypertension?

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Translational Neuroscience and Clinics 2017年第2期3卷 97-103页

作者： Yuanhan Yang Shyhjong Wu Chinchun Huang Jongling Fuh Chingkuan Liu Department of Neurology Kaohsiung Municipal Ta-Tung Hospital Kaohsiung Medical University Department of Master’s Program in Neurology Kaohsiung Medical University Department of Neurology Kaohsiung Medical University Hospital Kaohsiung Medical University Department of Medical Laboratory Science and Biotechnology Kaohsiung Medical University Department of Neurology Linkou Chang Gung Memorial Hospital Faculty of Medicine "National Yang-Ming University Schools of Medicine" Department of Neurology Neurological Institute Taipei Veterans General Hospital

Objective: angiotensin-converting enzyme(ACE) insertion/deletion(I/D) polymorphisms are considered biomarkers of late-onset Alzheimer's disease(AD). However, the results of studies of these polymorphisms have been inconsistent. The ACE protein directly degrades beta-amyloid and thereby slows the progression of AD and its onset. However, it also activates the renin–angiotensin–aldosterone system, which can contribute to hypertension and/or cardiovascular events that increase the risk for developing AD. Methods: In this study, we examined the bidirectional association of the ACE gene and AD in patients with AD with and without hypertension. Results: Patients who were clinically diagnosed with AD(n = 983) underwent ACE I/D genotyping. The distribution of the ACE I/D genotypes(P = 0.355 for I/I vs. D/D; P = 0.888 for I/D vs. D/D) and I alleles(P = 0.895) did not significantly differ between hypertensive patients with AD and patients with AD without hypertension. Conclusions: In contrast to traditional theories, the results of this study suggested that the contribution of the ACE gene to the development of AD was not associated with hypertension and similar cardiovascular effects.

关键词： angiotensin-converting enzyme Alzheimer’s disease hypertension beta-amyloid

Ethnic differences in the association between angiotensin-converting enzyme gene insertion/deletion polymorphism and peripheral vascular disease: A meta-analysis

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Chronic Diseases and Translational Medicine 2017年第4期3卷 230-241页

作者： Chao Han Xi-Kun Han Fang-Chao Liu Jian-Feng Huang Department of Epidemiology State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China

Background: Several studies have investigated the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with peripheral vascular disease (PVD); however, the results remain controversial. Therefore, we conducted the current meta-analysis to evaluate this relationship in the general population of different ethnicities. Methods: We searched PubMed, Embase, Web of Science, Wanfang Database, and CNKI to identify eligible studies. Random-effect models were applied to estimate the pooled odds ratio (OR) with a 95％ confidence interval (CI), regardless of between-study heterogeneity. Results: A total of 13 studies with 1966 cases and 6129 controls were included in this meta-analysis. The pooled ORs for the association between ACE I/D polymorphism and PVD risk were not statistically significant in the overall population under all genetic models. In further ethnicity-stratified analyses, we found a statistically significant association of ACE I/D polymorphism with PVD susceptibility in Asians under most models. However, the association among Caucasians did not reach statistical significance. Conclusion: ACE I/D polymorphism might be associated with susceptibility to PVD in the Asian population, but there was no clear evidence indicating a similar significant relationship among Caucasians.

关键词： Peripheral vascular disease angiotensin-converting enzyme Insertion/deletion polymorphism Meta-analysis

Interaction and Relationship Between angiotensin convertingenzyme Gene and Environmental Factors Predisposing toEssential Hypertension in MongolianPopulation of China

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Biomedical and Environmental Sciences 2004年第2期17卷 177-186页

作者： QUNXU YAN-HUAWANG WEI-JUNTONG MING-LIANGGU GANGWU BATUBUREN YONG-YUELIU JIANWANG YONG-SHANLI HUAFENG SHUANG-LIANBAI HAI-HUAPANG GUI-RONGHUANG MING-WUFANG YONG-HONGZHANG ZHENG-LAIWU CHANG-CHUNQIU NationalLaboratoryofMedicalMolecularBiology SchoolofBasicMedicinePekingCollegeInstituteofBasicMedicalSciencesChineseAcademyofMedicalSciencesBeijing100005China DepartmentofEpidemiology SchoolofBasicMedicinePekingUnionMedicalCollegeInstituteofBasicMedicalSciencesChineseAcademyofMedicalSciencesBeijing100005China DepartmentofEpidemiology PublicHealthSchoolHarbinMedicalUniversityHarbin150001HeilongjiangChina CenterforDiseaseControlandPreventionofTongliao Tongliao028000InnerMongoliaChina CenterHospitalofTongliao Tongliao028000InnerMongoliaChina CenterforDiseaseControlandPreventionofKezuohouqi Kezuohouqi028100InnerMongoliaChina

Objective To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China. Methods Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region. Results The association was found between ACE genotype DD plus ID and EH, with an interaction between ACE genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between ACE genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between ACE genotype and WHR on EH showed a multiplicative model. In a short, there was an interaction between ACE gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect Conclusion It is important for individuals who carry ACE D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention.

关键词： angiotensin-converting enzyme Hypertension Genetic Risk factors Interaction Exposure-gene effect

enzyme inhibitory activity of Dioscorea nipponica Makito hydroethanolic extracts of leaves and tubers in relation to their major secondary metabolites

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Food Bioscience 2022年第6期50卷 623-635页

作者： Aušra Adomėnienė Petras Rimantas Venskutonis Kaunas University of Technology Department of Food Science and TechnologyRadvilėnų pl.19KaunasLT-50254Lithuania

Different anatomical parts of Dioscorea nipponica Makito have been used in foods and folk medicines for their nutritional and pharmacological properties;however,the scientific data on enzyme inhibitory activities and phytochemicals in plant extracts remain rather *** information is important for expanding possible uses of plant origin preparations in *** study,using commonly applied assays,evaluated inhibitory activity of 70%ethanol extract of *** leaves and tubers against such physiologically important enzymes asα-amylase,α-glucosidase,acethylcholinesterase,and angiotensin-converting enzyme(ACE).Inhibition ofα-glucosidase and acethylcholinesterase required lower leaf extract concentrations as compared with other two *** IC50 values ofα-glucosidase andα-amylase inhibition were 66.08 and 438μg/mL,respectively,while the inhibition of ACE at 250–1250μg/mL was from 28.02±1.17%to 77.13±0.78%.The mode of inhibition ofα-glucosidase and acethylcholinesterase was evaluated by the kinetic *** and tuber extracts displayed a mixed-type non-competitive mode ofα-glucosidase *** composition of extracts was determined by UPLC-QTOF/MS and HPLC-UV *** extract was remarkably stronger enzyme inhibitor than tuber extract and it may be explained by the differences in the secondary metabolite ***,chlorogenic acids and quercetin glycosides,which are well-known enzyme inhibitors,were the main phytochemicals in the leaf extract,while steroidal glycosides,peptides and oligomeric sugars were the major constituents in the tuber *** is expected that new knowledge on *** will serve for its valorisation in developing new health beneficial ingredients for functional foods and nutraceuticals.

关键词： Yam α-Amylase α-Glucosidase Acethylcholinesterase angiotensin-converting enzyme Phytochemicals

Searching for a treatment for Alport syndrome using mouse models

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World Journal of Nephrology 2014年第4期3卷 230-236页

作者： Kan Katayama Shinsuke Nomura Karl Tryggvason Masaaki Ito Departmenof Cardiology and Nephrology Mie University Graduate Schoo of Medicine Division of Matrix Biology Department of Medical Biochemistry and Biophysics Karolinska Institute

Alport syndrome （AS） is a hereditary nephritis caused by mutations in COL4A3, COL4A4 or COL4A5 encod-ing the type IV collagen α3, α4, and α5 chains, which are major components of the glomerular basement membrane. About 20 years have passed since COL4A3, COL4A4, and COL4A5 were identifed and the frst Al-port mouse model was developed using a knockout ap-proach. The phenotype of Alport mice is similar to that of Alport patients, including characteristic thickening and splitting of the glomerular basement membrane. Alport mice have been widely used to study the patho-genesis of AS and to develop effective therapies. In this review, the newer therapies for AS, such as pharma-cological interventions, genetic approaches and stem cell therapies, are discussed. Although some stem cell therapies have been demonstrated to slow the renal disease progression in Alport mice, these therapies demand continual refnement as research advances. In terms of the pharmacological drugs, angiotensin-con-verting enzyme inhibitors have been shown to be effec-tive in Alport mice. Novel therapies that can provide a better outcome or lead to a cure are still awaited.

关键词： Alport syndrome angiotensin-converting enzyme Genetic Hereditary nephritis Pharmacologi-cal Renal injury Stem cell therapy