Antihypertensive Effect of Food-Origin Isothiocyanate Soluble Epoxide Hydrolase Inhibitors
食品源异硫氰酸酯可溶性环氧化物水解酶抑制剂的抗高血压作用
基本信息
- 批准号:10411131
- 负责人:
- 金额:$ 12.16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-20 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AcetylcholinesteraseAcidsAddressAdultAdverse effectsAffectAffinityAmericanAmerican Heart AssociationAngiotensin IIAnimal ModelAntihypertensive AgentsAntiinflammatory EffectAntioxidantsArachidonic AcidsBindingBiological AssayBloodBlood PressureBrassicaBroccoli - dietaryCabbage - dietaryCardiovascular DiseasesCauliflowerCause of DeathCessation of lifeChemopreventionChronicClinical SciencesConsumptionCoronary arteryCoronary heart diseaseCytochrome P450CytosolDeath RateDevelopmentDietDockingDoctor of PharmacyDoseDrug InteractionsDrug KineticsEffectivenessEndotheliumEnrollmentEnzymesEpoxide hydrolaseEpoxy CompoundsFamilyFatty AcidsFemaleFluorescenceFoodFunctional disorderGoalsHealthcareHorseradishHumanHypertensionInbred SHR RatsIncidenceIncubatedIndividualInflammationIsothiocyanatesKale - dietaryKidneyKineticsLaboratoriesLepidium sativumLiverMeasuresModelingMolecularMonophenol MonooxygenaseMorbidity - disease rateMustardNatural ProductsNatureOralOxidative StressPathogenesisPatientsPersonsPharmaceutical PreparationsPharmacologyPhenethyl IsothiocyanatePlantsPlayPopulationPropertyRattusReadinessRecombinantsRegulationResearchResearch InfrastructureResearch TrainingResourcesRiskRoleSodium ChlorideStrokeStudentsSulforaphaneTestingTherapeuticTissuesTreatment CostUncertaintyUninsuredUnited StatesUniversitiesVegetablesWatercressallyl isothiocyanateanalogbasebenzyl isothiocyanateblood pressure reductioncardiovascular risk factorcostcruciferous vegetabledietarygraduate studenthigh riskhypertensiveimprovedin vivoinhibitorkidney vascular structuremaleminimal riskmortalitynovelpharmacokinetic characteristicpreventside effectskillstherapeutic targettraining opportunityundergraduate student
项目摘要
PROJECT SUMMARY/ABSTRACT
It is estimated that hypertension affects nearly one third of adult Americans (approximately 75 million persons).
Unfortunately, whether the hypertension is treated or not, only approximately 50% of adults with hypertension
have their blood pressure controlled and therefore have higher risk of cardiovascular morbidity and mortality as
well as increased use of health care resources. Hypertension was listed as the leading or contributing cause of
death in more than 470,000 Americans in 2019 leading to a death rate of 19.9 per 100,000. In 2012, the
calculated total cost of treating hypertension in the US was $51.2 billion and the American Heart Association
(AHA) estimates that the total cost of treating hypertension in the US in 2025 will be $225 billion. In the last five
years, our laboratory has been investigating newer and safer agents from nature that have the potential to treat
and/or protect against hypertension. We have demonstrated that chronic administration of sulforaphane (SF), an
isothiocyanate (ITC), to young spontaneously hypertensive rats (SHR) results in preventing the progressive rise
in blood pressure in this animal model. The observed antihypertensive effect of the examined ITC was
significantly correlated with inhibition of the renal soluble epoxide hydrolase (sEH), a key enzyme in metabolizing
endogenously derived fatty acid epoxide and considered an important therapeutic target in a wide range of
human cardiovascular diseases. Since ITCs are natural products and rich in the diet, they can provide a viable
option for hypertensive patients and prehypertensive individuals who are unable or unwilling to use current
antihypertensive agents because of their cost, adverse effects, or risk of drug-drug interactions. These
individuals will not only benefit from the potential antihypertensive effect of ITCs, but also receive the
documented chemoprevention, antioxidant, and anti-inflammatory effects associated with their use. The
objective of this proposal is to study the sEH inhibition and blood pressure lowering effects of several naturally-
occurring ITCs, and to identify the structural factors that modulate their effectiveness as sEH inhibitors. The
positive impact of this research is to identify potent antihypertensive ITCs with favorable pharmacokinetic
properties and affordable cost. Specific Aim 1 will evaluate the potency, selectivity, and mechanism of inhibition
of human and rat sEH by ITCs. Specific Aim 2 will investigate the anti-hypertensive effect of the most active ITC
compound in SHR. This application offers excellent research training opportunities for undergraduate and
graduate students, furthers and strengthens Dr. Elbarbry and his team’s research skills and preparedness for
other proposals, and will make significant contributions to the enhancement of the Pacific University’s research
infrastructure.
项目总结/摘要
据估计,高血压影响近三分之一的成年美国人(约7500万人)。
不幸的是,无论高血压是否得到治疗,只有大约50%的成年高血压患者
血压得到控制,因此心血管发病率和死亡率风险较高,
增加医疗资源的使用。高血压被列为导致
2019年,超过47万美国人死亡,死亡率为每10万人19.9人。2012年
据计算,美国治疗高血压的总费用为512亿美元,美国心脏协会
(AHA)据估计,到2025年,美国治疗高血压的总成本将达到2250亿美元。在过去五
多年来,我们的实验室一直在研究来自自然界的更新和更安全的药物,这些药物有可能治疗
和/或防止高血压。我们已经证明,长期服用萝卜硫素(SF),
异硫氰酸酯(ITC),对年轻的自发性高血压大鼠(SHR)的结果,防止进行性上升
在这个动物模型的血压中。观察到的ITC的抗高血压作用是
与肾脏可溶性环氧化物水解酶(sEH)的抑制显著相关,sEH是代谢的关键酶,
内源性衍生的脂肪酸环氧化物,并被认为是广泛的治疗靶点。
人类心血管疾病由于ITC是天然产物并且在饮食中丰富,它们可以提供可行的
对于不能或不愿使用本品的高血压患者和高血压前期个体,
抗高血压药物,因为它们的成本,副作用或药物相互作用的风险。这些
个体不仅将受益于ITC的潜在抗高血压作用,
记录了与其使用相关的化学预防、抗氧化和抗炎作用。的
本提案的目的是研究几种天然-
发生ITCs,并确定调节其作为sEH抑制剂的有效性的结构因素。的
这项研究的积极影响是确定具有良好药代动力学的有效抗高血压ITC
性能和负担得起的成本。具体目标1将评价抑制效力、选择性和机制
人和大鼠sEH的ITCs。具体目标2将研究最活跃的ITC的抗高血压作用
化合物在SHR中的作用。该应用程序为本科生提供了极好的研究培训机会,
研究生,进一步加强和Elbarbry博士和他的团队的研究技能和准备,
其他建议,并将作出重大贡献,以加强太平洋大学的研究
基础设施演进
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Fawzy Elbarbry其他文献
Fawzy Elbarbry的其他文献
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{{ truncateString('Fawzy Elbarbry', 18)}}的其他基金
Antihypertensive Effect of Food-Origin Isothiocyanate Soluble Epoxide Hydrolase Inhibitors
食品源异硫氰酸酯可溶性环氧化物水解酶抑制剂的抗高血压作用
- 批准号:
10706992 - 财政年份:2022
- 资助金额:
$ 12.16万 - 项目类别:
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