Strategies to Investigate Synergy in Botanical Medicines

研究植物药协同作用的策略

• 批准号: 8443080
• 负责人: Nadja B Cech
• 金额: $ 36.95万
• 依托单位: UNIVERSITY OF NORTH CAROLINA GREENSBORO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8443080
• 关键词: AIDS/HIV problem; Accounting; Acquired Immunodeficiency Syndrome; Adjuvant; Alkaloids; Alternative Medicine; Anti-Bacterial Agents; Antibiotics; Attenuated; Bacteria; Bacterial Infections; Berberine Alkaloids; Biological; Biological Assay; Biological Markers; Botanicals; Child; Clinical; Complementary and alternative medicine; Data; Drug resistance; Epidemic; Flavonoids; Fractionation; Goals; Goldenseal; Head; Healthcare; Herbal Medicine; Human; In Vitro; Individual; Infection; Investigation; Kinetics; Laboratories; Mass Spectrum Analysis; Medicinal Plants; Medicine; Methicillin Resistance; Methods; Modeling; Outcome; Pathogenesis; Philosophy; Plant Extracts; Plants; Play; Preparation; Prevention; Principal Investigator; Process; Proteins; Public Health; Publishing; Pump; Quality Control; Reporter Genes; Research; Research Personnel; Resistance development; Role; Signal Transduction; Skin; Standardization; Staphylococcus aureus; Structure; System; Testing; Therapeutic Uses; Topical Preparation; Treatment Efficacy; Virulence; Work; World Health Organization; antimicrobial; base; combat; dietary supplements; drug candidate; efflux pump; fighting; in vivo; inhibitor/antagonist; innovation; insight; keratinocyte; killings; methicillin resistant Staphylococcus aureus; pathogen; pathogenic bacteria; prevent; public health relevance; quorum sensing; research study

DESCRIPTION (provided by applicant): The problem of drug-resistant bacterial infections has reached epidemic proportions. Methicillin-resistant Staphyolcoccus aureus (MRSA) infections now kill more US citizens each year than does AIDS, and new strategies to treat or prevent such infections are greatly needed. This issue is compounded by a lack of new drug candidates in the pipeline, and the fact that bacteria very quickly develop resistance to new antibiotics. With this project, we propose to explore an alternative strategy for combating bacterial infections, the use of a botanical medicine containing multiple different compounds with diverse modes of action. The botanical under investigation is goldenseal (Hydrastis canadensis), which has been used in traditional and modern alternative medicine to treat infections. Goldenseal is a significant topic of study because of its popularity as a dietary supplement (among the top 15 best-selling botanical medicines in the US, and the 6th most commonly used by children). This plant or its constituents have demonstrated antimicrobial activity in numerous in vitro and several in vivo studies. Our strong preliminary data provide new insights into the mechanisms by which goldenseal acts against bacteria. We have shown that this plant contains a diverse array of bioactive constituents, which can act as direct antimicrobia agents, as efflux pump inhibitors, and as anti-virulence compounds (via quorum quenching). A major goal of this application is to identify the constituents that contribute to these diverse activities. To accomplish this, we will employ an innovative approach, synergy-directed fractionation, which has recently been developed and published by the principal investigator's laboratory. Our long term objective is to use the information provided by these studies to enable the preparation of topical goldenseal preparations with optimal efficacy for the treatment or prevention of bacterial infections. More broadly, we also seek to explore one of the major guiding principles of complementary and alternative medicine, that the activity of multi-component therapies can be enhanced due to synergistic interactions. The methods validated as a part of this study are expected to prove useful to other investigators who must account for the synergistic interactions that play a role in the activity of many botanical medicines.

描述（由申请人提供）：耐药细菌感染的问题已经达到流行病的程度。耐甲氧西林金黄色葡萄球菌（MRSA）感染现在每年杀死更多的美国公民比艾滋病，和新的策略来治疗或预防这种感染是非常需要的。由于缺乏新的候选药物，以及细菌很快对新抗生素产生耐药性的事实，这个问题变得更加复杂。通过这个项目，我们建议探索一种对抗细菌感染的替代策略，使用含有多种不同作用模式的多种不同化合物的植物药。正在调查的植物是白毛茛（Hydrastis canadensis），它已被用于传统和现代替代医学来治疗感染。毛茛是一个重要的研究课题，因为它作为一种膳食补充剂很受欢迎（美国最畅销的15种植物药之一，儿童最常用的第6种）。这种植物或其成分已在许多体外和几项体内研究中证明了抗微生物活性。我们强大的初步数据提供了新的见解的机制，其中白毛茛对细菌的行为。我们已经表明，这种植物含有多种生物活性成分，可以作为直接的抗菌剂，作为外排泵抑制剂，并作为抗毒性化合物（通过群体淬灭）。该应用程序的主要目标是识别有助于这些不同活动的成分。为了实现这一目标，我们将采用一种创新的方法，协同导向分馏，这是最近开发和出版的主要研究者的实验室。我们的长期目标是利用这些研究提供的信息，能够制备具有最佳疗效的局部白毛茛制剂，用于治疗或预防细菌感染。更广泛地说，我们还寻求探索补充和替代医学的主要指导原则之一，即由于协同作用，多组分疗法的活性可以得到增强。作为本研究的一部分验证的方法预计将证明对其他研究人员有用，他们必须考虑在许多植物药的活性中发挥作用的协同相互作用。