Effects of digestion on composition and bioavailability of compounds from Ashwagandha: an in vitro study

消化对 Ashwagandha 化合物的组成和生物利用度的影响：一项体外研究

• 批准号: 10711567
• 负责人: Wendy Strangman
• 金额: $ 7.41万
• 依托单位: UNIVERSITY OF NORTH CAROLINA WILMINGTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711567
• 关键词: Affect; Animals; Antidepressive Agents; Anxiety; Artificial Membranes; Ashwagandha; Ayurvedic Medicine; Biological Assay; Biological Availability; Biological Models; Blood Circulation; Botanical dietary supplements; Cell Membrane Permeability; Cellular Assay; Chemical Structure; Chemicals; Circulation; Clinical; Cognition; Complex; Complex Mixtures; Consumption; Coupled; Data; Deterioration; Diffusion; Digestion; Drosophila genus; Drug Industry; Environment; Enzymes; Evaluation; Future; Health; Health Benefit; In Vitro; Incubated; Individual; Industry Standard; Ingestion; Intestinal Absorption; Intestines; Investigation; Laboratories; Liquid Chromatography; Liquid substance; Marketing; Mass Spectrum Analysis; Medicine; Membrane; Metabolic; Methods; Modeling; Names; National Center for Complementary and Integrative Health; Natural Products; Natural Remedy; Neurologic; Oral; Outcome Study; Permeability; Pharmaceutical Preparations; Pharmacologic Substance; Plant Leaves; Preparation; Process; Property; Protocols documentation; Public Health; Reaction; Reporting; Research; Resolution; Resources; Standardization; Statistical Data Interpretation; Testing; Time; absorption; age related; aqueous; dietary supplements; gastrointestinal; gut microbiome; improved; in vitro Assay; in vitro Model; in vivo; innovation; insight; interest; maternal compound W; metabolic profile; metabolomics; passive transport; pre-clinical; pressure; resilience; sleep quality; time use

Abstract Withania somnifera, has long been known in Ayurvedic medicine for its medicinal properties. In recent years, consumption of W. somnifera products has skyrocketed in western cultures where they are now marketed through retail outlets as dietary supplements, under the common name, Ashwagandha. The NCCIH-sponsored BENFRA Botanical Dietary Supplements Research Center (U19 AT010829) is currently researching Ashwagandha, to determine its effects on age-related neurological deterioration. Unlike pharmaceutical drugs which have an extensive evaluation process prior to public distribution, very little is known regarding how the complex mixture of chemicals present in Ashwagandha extracts behaves once it is consumed and passes through the digestive environment. This proposal is innovative because it will evaluate metabolic stability of Ashwagandha extracts for the first time using in vitro laboratory models simulating the gastrointestinal environment. The project will also assess which original or modified components are able to pass the intestinal membrane via passive diffusion, the mechanism by which most compounds enter the circulation from the gut. The central hypothesis of this research is that the composition of Ashwagandha derived metabolites entering circulation is markedly different from that of the original extract. This hypothesis will be tested through the following specific aims: 1. Determine effects of gastrointestinal environments on the metabolite profiles of Ashwagandha extracts by exposing extracts to simulated gastro-intestinal fluids and enzymes; and 2. Identify permeabilities of metabolites from Ashwagandha original extracts and digestive incubations using a synthetic model of the intestinal membrane. We will use a combination of these in vitro model systems, appropriate controls, and sufficient replicates for robust statistical analyses to standardize these initial investigations. Ultra- pressure liquid chromatography coupled with high resolution mass spectrometry will be used to analyze extracts, incubates, and diffusion chamber media, to evaluate changes in chemical structures and relative abundances of Ashwagandha metabolites in these complex matrices for the first time. Results from these studies will provide insight into a more realistic Ashwagandha metabolic profile post-gastrointestinal digestion that can then be further studied collaboratively using established pre-clinical assays. Results of the present study may also highlight permeable metabolites of interest not currently under investigation for bioactivity. In the long term, this project will establish a robust analytical strategy that can be used broadly to assess oral bioavailability of other botanical supplements in an in vitro setting, prior to time, labor, and resource intensive in vivo studies.

抽象的 睡茄在阿育吠陀医学中因其药用特性而闻名。最近几年， 在西方文化中，睡眠睡莲产品的消费量猛增 通过零售店作为膳食补充剂，通用名 Ashwagandha。 NCCIH 主办 BENFRA 植物膳食补充剂研究中心 (U19 AT010829) 目前正在研究 Ashwagandha，以确定其对与年龄相关的神经功能恶化的影响。与药品不同 在公开发行之前有一个广泛的评估过程，但人们对如何 Ashwagandha 提取物中存在的化学物质的复杂混合物一旦被消耗并通过就会表现出行为 通过消化环境。该提案具有创新性，因为它将评估代谢稳定性 首次使用模拟胃肠道的体外实验室模型提取南非醉茄提取物 环境。该项目还将评估哪些原始或改良成分能够通过肠道 通过被动扩散形成膜，这是大多数化合物从肠道进入循环的机制。 这项研究的中心假设是 Ashwagandha 衍生的代谢物的成分进入 循环与原始提取物明显不同。这一假设将通过 以下具体目标： 1. 确定胃肠道环境对代谢物谱的影响 通过将提取物暴露于模拟胃肠液和酶中来提取南非醉茄； 2. 识别 Ashwagandha 原始提取物的代谢物的渗透性和使用合成物的消化孵化 肠膜模型。我们将使用这些体外模型系统的组合，适当 控制，并进行足够的重复以进行稳健的统计分析，以使这些初步调查标准化。极端主义者- 压力液相色谱法与高分辨率质谱法相结合将用于分析提取物， 孵化和扩散室介质，以评估化学结构和相对丰度的变化 Ashwagandha 首次在这些复杂的基质中进行代谢。这些研究的结果将提供 深入了解更真实的 Ashwagandha 胃肠道消化后代谢情况，然后可以 使用已建立的临床前测定进一步合作研究。本研究的结果也可能 突出显示目前尚未进行生物活性研究的感兴趣的可渗透代谢物。从长远来看，这 项目将建立一个强大的分析策略，可广泛用于评估其他药物的口服生物利用度 在时间、劳动力和资源密集型体内研究之前，在体外环境中使用植物补充剂。