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 Withania Somnifera长期以来一直以其药用特性而闻名。最近几年， W. Somnifera产品的消费在现在被销售的西方文化中飙升 通过零售店作为饮食补品，以普通名称为Ashwagandha。 NCCIH赞助 Benfra植物饮食补充剂研究中心（U19 AT010829）目前正在研究 Ashwagandha，确定其对年龄相关的神经系统恶化的影响。与药物不同 在公开分销之前有广泛的评估过程，关于如何如何 消耗后，Ashwagandha提取物中存在的化学物质的复杂混合物的行为并通过 通过消化环境。该建议具有创新性，因为它将评估 Ashwagandha首次使用模拟胃肠道的体外实验室模型首次提取 环境。该项目还将评估哪些原始或修改的组件能够通过肠道 膜通过被动扩散，大多数化合物从肠道中进入​​循环的机制。 这项研究的核心假设是，阿什瓦甘达（Ashwagandha）衍生代谢物的组成 循环与原始提取物的循环明显不同。该假设将通过 以下特定目的：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的胃肠道液和酶来提取提取物；和2。识别 使用合成的Ashwagandha原始提取物和消化孵育的代谢产物的渗透率 肠膜的模型。我们将结合这些体外模型系统，适当 对照和足够的重复进行可靠的统计分析，以标准化这些初步研究。极端主义者- 压力液相色谱和高分辨率质谱法将用于分析提取物， 孵化和扩散室培养基，以评估化学结构的变化和相对丰度 这些复杂矩阵中的Ashwagandha代谢产物首次在这些复杂矩阵中。这些研究的结果将提供 深入了解更现实的Ashwagandha代谢概况，后期消化后可以是 进一步使用既定的临床前测定法进行了协作。本研究的结果也可能 突出了目前尚未研究生物活性的可渗透代谢物。从长远来看，这个 项目将建立强大的分析策略，可广泛用于评估其他的口服生物利用度 在体外研究之前，时间和资源大量研究之前，植物补充剂在体外研究之前。