Contributions of host and gut microbial mediated metabolism to the antiviral activity of elderberry

宿主和肠道微生物介导的代谢对接骨木浆果抗病毒活性的贡献

• 批准号: 10723102
• 负责人: William Joseph Crandall
• 金额: $ 4.77万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723102
• 关键词: Accounting; Address; Adoxaceae; Anthocyanins; Antiviral Agents; Biological; Biological Availability; Biological Models; Botanical dietary supplements; Botanicals; COVID-19 outbreak; Cell model; Chemical Structure; Chemicals; Complex; Coupled; Crude Extracts; Cytochrome P450; Development; Drug Kinetics; Elderberry; Environment; Enzymes; Exhibits; Flavanol; Follow-Up Studies; Foundations; Germ-Free; Gnotobiotic; Goals; Health; Healthcare; Hepatic; Herbal Medicine; Herbal supplement; High Pressure Liquid Chromatography; Human; Human Microbiome; Human body; In Vitro; Influenza; Infrastructure; Ingestion; Investigation; Knowledge; Liver; Marketing; Mass Spectrum Analysis; Mediating; Medicine; Mentors; Metabolic; Metabolic Biotransformation; Metabolism; Methods; Modeling; Mus; Natural Products; Nuclear Magnetic Resonance; Pharmaceutical Preparations; Pharmacognosy; Pharmacology; Physiological; Play; Population; Prodrugs; Public Health; Reaction; Research; Research Training; Resolution; Role; Safety; Sales; Sambucus nigra; Scientist; Standardization; Sulfate; Techniques; Testing; Training; Translations; United States; Urine; Viral; Viral Physiology; X-Ray Crystallography; absorption; anti-influenza; anti-viral efficacy; bacteriome; career; career development; defined contribution; dietary supplements; drug metabolism; experimental study; flu activity; gut microbiome; improved; in vitro Model; in vivo; influenza infection; metabolic profile; metabolomics; microbial; microbiome; microbiota; mouse model; novel; oxidation; pharmacokinetics and pharmacodynamics; pharmacologic; polyphenol; response; tandem mass spectrometry; ultra high pressure; virology

ABSTRACT Herbal dietary supplements and medicines are used as the primary form of health care for about eighty percent of the world’s population. In the United States, the use of these botanicals is increasing, accounting for $11.26 billion in sales in the past year alone. Despite widespread and increasing use, herbal dietary supplements and medicines are severely underregulated compared to western medicine. Exact mechanisms, active compounds and metabolites, pharmacokinetics, and safety profiles are not fully understood. This study focuses on the top- selling herbal dietary supplement in the year 2020 in the United States, elderberry (Sambucus nigra L.), which exhibits antiviral effects. Many natural products can exhibit poor bioavailability and thus despite the promise of antiviral efficacy in vitro, do not equate to relevant pharmacological effects in vivo. Metabolic degradation products resulting from host metabolism or gut microbiome metabolism can, however, exhibit increased bioavailability and pharmacological effects. Few studies have examined the metabolic products, bioavailability, and pharmacological effects of metabolites of elderberry, and none have done so when regarding its antiviral activities. Thus, this proposal provides novel research training in pharmacokinetics and pharmacognosy to test metabolic biotransformation products of elderberry extracts for antiviral efficacy. This proposal will develop the methods and capabilities for host and gut microbial metabolism of complex botanical mixtures and provide pharmacological significance regarding the antiviral efficacy of elderberry. Metabolic products of elderberry will be characterized in vitro models and validated in vivo. Isolation of metabolites generated will be conducted using preparative high-performance liquid chromatography and their antiviral activity assessed against influenza models. Antiviral compounds and metabolites will be characterized using high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR), and X-ray crystallography where applicable. Bioavailability and contributions of the gut microbiome will be assessed using a gnotobiotic murine model. These studies will identify metabolites from elderberry exhibiting both antiviral capacities and bioavailability and help establish an infrastructure for metabolic assessment of other botanicals. This will advance the understanding and characterization of herbal medicines and promote the development of my career as an independent scientist capable of conducting relevant research in the fields of pharmacognosy and pharmacology to benefit human health.

抽象的 草药饮食补充剂和药物被用作医疗保健的主要形式，约占百分之八。 世界人口。在美国，这些植物会的使用正在增加，算出11.26美元 仅在过去的一年中，十亿美元的销售额。尽管宽度和使用越来越多，但草药饮食补充剂和 与西药相比，药物严重调节。确切的机制，活性化合物 以及代谢物，药代动力学和安全概况尚不完全了解。这项研究的重点是顶部 在2020年在美国出售草药饮食补充剂，Enterberry（Sambucus nigra L.） 表现出抗病毒作用。许多天然产品可以表现出差的生物利用度，从而渴望 体外的抗病毒效率，不等于体内相关的药物效应。代谢降解 然而，由宿主代谢或肠道微生物组代谢产生的产品可能会增加 生物利用度和药物效应。很少有研究检查了代谢产品，生物利用度， 以及接骨木浆果的代谢产物的药物效应，关于其抗病毒 活动。这是该提案提供了药代动力学和药物认知的新型研究培训 接骨病毒提取物的代谢生物转化产物，以提高抗病毒效率。该建议将发展 复杂植物混合物的宿主和肠道微生物代谢的方法和能力，并提供 关于接骨木浆果的抗病毒效率的药理学意义。接骨木浆果的代谢产品将 在体外模型中进行表征并在体内进行验证。生成的代谢物的隔离将使用 对影响的制备高性液相色谱法及其抗病毒活性 型号。使用高分辨率质谱法对抗病毒化合物和代谢产物进行表征 （HRMS），核磁共振（NMR）和X射线晶体学（适用）。生物利用度和 肠道微生物组的贡献将使用gnotobiotic鼠模型进行评估。这些研究将确定 接骨木莓的代谢产物表现出抗病毒能力和生物利用度，并有助于建立 用于其他植物学代谢评估的基础设施。这将提高理解和 描述草药并促进我作为独立科学家职业的发展 能够在药学和药理学领域进行相关研究以使人类受益 健康。