Evaluation of the potential of Ashwagandha extracts to produce CYP-mediated drug interactions.
评估 Ashwagandha 提取物产生 CYP 介导的药物相互作用的潜力。
基本信息
- 批准号:10436380
- 负责人:
- 金额:$ 7.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdverse effectsAffectAgingAshwagandhaBiological AssayBotanical dietary supplementsBotanicalsCYP1A2 geneCYP2B6 geneCYP2C19 geneCYP2C9 geneCYP2D6 geneCYP2E1 geneCYP3A4 geneCarrier ProteinsChemicalsClinical ResearchClinical TrialsCognitionCognitiveComplexCytochrome P450DangerousnessDataDatabasesDepositionDrug EvaluationDrug InteractionsDrug KineticsElderlyEnsureEnzymesEuterpeEvaluationFundingFutureHealthHealth SciencesHepaticHepatocyteHumanIn VitroInvestigationIsoenzymesKnowledgeLaboratoriesLiver MicrosomesMeasuresMediatingMessenger RNAMetabolismMethanolNational Center for Complementary and Integrative HealthNatural Product DrugNatural ProductsNatural Products ChemistryNeurologicNuclear ReceptorsOregonOutcomePeer ReviewPharmaceutical PreparationsPharmacognosyPharmacy SchoolsPhasePilot ProjectsPlant LeavesPlant RootsPoliciesPopulationProtein IsoformsPublicationsPublishingReportingResearchResearch PersonnelResourcesReverse Transcriptase Polymerase Chain ReactionRiskSleepSleeplessnessStressTestingTherapeutic AgentsTimeUnited StatesUnited States National Institutes of HealthUniversitiesVeterinary MedicineWorkage groupaqueousbasecollegedietary supplementsdrug developmentdrug metabolismenzyme activityimprovedmRNA Expressionnovel therapeuticsresilienceresponse
项目摘要
Project Summary
Although drug-drug interactions are routinely evaluated during new drug development, the potential for
botanicals and botanical dietary supplements to cause natural product-drug interactions is rarely evaluated. To
correct this deficiency, we are responding to the PAR-20-228: Pilot Projects Increasing the Impact of the NIH
Centers for Advancing Research on Botanicals and Other Natural Products (PI2 CARBON). Specifically, we
propose to evaluate Ashwagandha (Withania somnifera), one of the top 40 selling botanicals used by US
consumers in 2018, for inhibition and induction of the most important Phase I drug metabolizing enzymes, the
cytochromes P450 (CYPs). To date, there have been limited reports regarding the inhibitory effects of
Ashwagandha extracts on the CYPs, and no published studies examined whether Ashwagandha extracts have
the potential to induce CYP expression. Ashwagandha is used by older adults in particular to ameliorate stress,
insomnia, and cognitive deficiencies; and this population is often taking conventional medications for other
health conditions. Thus, use by the elderly makes a study of how Ashwagandha affects CYP activity and
expression an important concern. Ashwagandha is one of two botanicals being studied for its ability to improve
resilience in the BENFRA Botanical Dietary Supplements Research Center (BDSRC) at Oregon Health and
Science University (U19 AT010829). Our work will synergize with that of the BENFRA BDSRC, which will
provide authenticated and chemically characterized extracts of Ashwagandha roots and leaves for testing in
the applicant’s laboratory at the University of Auburn. For our project, we propose two Specific Aims. In Aim 1,
we will screen different types of Ashwagandha extracts for inhibition of 9 human hepatic CYPs (including all
CYPs recommended for drug-drug evaluation by the FDA). Inhibition of CYPs in pooled human liver
microsomes will be measured using CYP probe substrates and our ultrafast UHPLC-MS/MS cocktail assay. In
Aim 2, we will assess induction of CYP mRNA expression caused by Ashwagandha extracts using primary
human hepatocytes in sandwich culture according to the FDA Guidance on in vitro drug-drug interactions
studies. The resulting comprehensive data of Ashwagandha extract-CYP interactions will be made available
through scientific publications. Demonstration of inhibition or induction of CYPs by Ashwagandha will be
followed by future studies that seek to identify the compounds responsible for the observed effects.
Demonstration of interactions with CYP enzymes will be followed by confirmatory clinical studies of
Ashwagandha-drug pharmacokinetic interactions.
项目概要
尽管在新药开发过程中会定期评估药物间相互作用,但潜在的
植物药和植物膳食补充剂引起天然产品-药物相互作用的研究很少被评估。到
为了纠正这一缺陷,我们正在响应 PAR-20-228:提高 NIH 影响力的试点项目
植物药和其他天然产品研究推进中心 (PI2 CARBON)。具体来说,我们
提议评估 Ashwagandha(Withania somnifera),美国最畅销的 40 种植物药之一
2018年,为了抑制和诱导最重要的一期药物代谢酶,
细胞色素 P450 (CYP)。迄今为止,关于其抑制作用的报道还很有限。
Ashwagandha 提取物对 CYP 的影响,并且没有发表的研究检验 Ashwagandha 提取物是否具有
诱导 CYP 表达的潜力。 Ashwagandha 特别被老年人用来缓解压力,
失眠和认知缺陷;该人群经常服用其他药物来治疗
健康状况。因此,老年人的使用研究了 Ashwagandha 如何影响 CYP 活性和
表达了一个重要的关切。 Ashwagandha 是正在研究的两种植物之一,其能够改善
俄勒冈州卫生局 BENFRA 植物膳食补充剂研究中心 (BDSRC) 的复原力
科学大学(U19 AT010829)。我们的工作将与 BENFRA BDSRC 的工作产生协同作用,后者将
提供经过验证和化学表征的 Ashwagandha 根和叶提取物,用于测试
申请人在奥本大学的实验室。对于我们的项目,我们提出了两个具体目标。在目标 1 中,
我们将筛选不同类型的 Ashwagandha 提取物对 9 种人肝 CYP 的抑制作用(包括所有
FDA 推荐用于药物间评价的 CYP)。混合人肝脏中 CYP 的抑制
将使用 CYP 探针底物和我们的超快 UHPLC-MS/MS 鸡尾酒测定来测量微粒体。在
目标 2,我们将使用初级评估 Ashwagandha 提取物引起的 CYP mRNA 表达诱导
根据 FDA 体外药物相互作用指南进行夹心培养的人肝细胞
研究。 Ashwagandha 提取物与 CYP 相互作用的综合数据将可供使用
通过科学出版物。 Ashwagandha 对 CYP 的抑制或诱导作用将被证明
接下来是未来的研究,旨在找出造成所观察到的影响的化合物。
与 CYP 酶相互作用的证明之后将进行验证性临床研究
Ashwagandha 药物药代动力学相互作用。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Robert D Arnold其他文献
Prospective pilot study evaluating a vitamin D3 loading dose in critically ill children with vitamin D deficiency
评估维生素 D3 负荷剂量对维生素 D 缺乏症危重儿童的前瞻性试点研究
- DOI:
- 发表时间:
2023 - 期刊:
- 影响因子:2.9
- 作者:
Elizabeth W. Covington;Shaneese L Jasper;Robert D Arnold;Raj Amin;Susan Egbert;Allison Chung - 通讯作者:
Allison Chung
Robert D Arnold的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Robert D Arnold', 18)}}的其他基金
Evaluation of the potential of Ashwagandha extracts to produce CYP-mediated drug interactions.
评估 Ashwagandha 提取物产生 CYP 介导的药物相互作用的潜力。
- 批准号:
10271857 - 财政年份:2021
- 资助金额:
$ 7.45万 - 项目类别:
Secretory Phospholipases sPLA2 and their Receptors for Delivering Nanoparticles
分泌型磷脂酶 sPLA2 及其用于递送纳米颗粒的受体
- 批准号:
8419881 - 财政年份:2013
- 资助金额:
$ 7.45万 - 项目类别:
Secretory Phospholipases sPLA2 and their Receptors for Delivering Nanoparticles
分泌型磷脂酶 sPLA2 及其用于递送纳米颗粒的受体
- 批准号:
8777093 - 财政年份:2013
- 资助金额:
$ 7.45万 - 项目类别:
Secretory Phospholipases sPLA2 and their Receptors for Delivering Nanoparticles
分泌型磷脂酶 sPLA2 及其用于递送纳米颗粒的受体
- 批准号:
8601531 - 财政年份:2013
- 资助金额:
$ 7.45万 - 项目类别:
相似海外基金
Unraveling Adverse Effects of Checkpoint Inhibitors Using iPSC-derived Cardiac Organoids
使用 iPSC 衍生的心脏类器官揭示检查点抑制剂的副作用
- 批准号:
10591918 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
Optimization of mRNA-LNP vaccine for attenuating adverse effects and analysis of mechanism behind adverse effects
mRNA-LNP疫苗减轻不良反应的优化及不良反应机制分析
- 批准号:
23K15383 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of adverse effects of combined exposure to low-dose chemicals in the living environment on allergic diseases and attempts to reduce allergy
阐明生活环境中低剂量化学品联合暴露对过敏性疾病的不良影响并尝试减少过敏
- 批准号:
23H03556 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Green tea-based nano-enhancer as an adjuvant for amplified efficacy and reduced adverse effects in anti-angiogenic drug treatments
基于绿茶的纳米增强剂作为抗血管生成药物治疗中增强疗效并减少不良反应的佐剂
- 批准号:
23K17212 - 财政年份:2023
- 资助金额:
$ 7.45万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Effects of Tobacco Heating System on the male reproductive function and towards to the reduce of the adverse effects.
烟草加热系统对男性生殖功能的影响以及减少不利影响。
- 批准号:
22H03519 - 财政年份:2022
- 资助金额:
$ 7.45万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Mitigating the Adverse Effects of Ultrafines in Pressure Filtration of Oil Sands Tailings
减轻油砂尾矿压力过滤中超细粉的不利影响
- 批准号:
563657-2021 - 财政年份:2022
- 资助金额:
$ 7.45万 - 项目类别:
Alliance Grants
1/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
1/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10521849 - 财政年份:2022
- 资助金额:
$ 7.45万 - 项目类别:
4/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
4/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10671022 - 财政年份:2022
- 资助金额:
$ 7.45万 - 项目类别:
2/4 Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
2/4 ECT 结果和不良反应的破译机制(DECODE)
- 批准号:
10670918 - 财政年份:2022
- 资助金额:
$ 7.45万 - 项目类别:
Downsides of downhill: The adverse effects of head vibration associated with downhill mountain biking on visuomotor and cognitive function
速降的缺点:与速降山地自行车相关的头部振动对视觉运动和认知功能的不利影响
- 批准号:
2706416 - 财政年份:2022
- 资助金额:
$ 7.45万 - 项目类别:
Studentship