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达到流行病的比例。现在，抗甲氧西林金黄色葡萄球菌（MRSA）感染现在每年杀死的美国公民多于艾滋病，并且非常需要治疗或预防这种感染的新策略。这个问题是由于管道中缺乏新药的候选物而更加复杂的，而且细菌很快就会产生对新抗生素的抗性。在这个项目中，我们建议探索一种打击细菌感染的替代策略，即使用含有多种不同作用模式的植物医学。正在研究的植物性是金eseal（Hydreastis canadensis），该植物已在传统和现代替代医学中用于治疗感染。金esheal是一个重要的研究主题，因为它是饮食补充剂的知名度（在美国最畅销的植物药最畅销的15种，也是儿童最常用的第六种）。该植物或其成分在许多体外和几项体内研究中表现出抗菌活性。我们强大的初步数据提供了有关戈德米对细菌作用的机制的新见解。我们已经表明，该植物包含多种生物活性成分，可以充当直接的抗微生物剂，作为外排泵抑制剂和抗病毒剂化合物（通过法定淬火）。该应用程序的主要目的是确定对这些不同活动的贡献。为了实现这一目标，我们将采用一种创新的方法，即协同指导的分馏，该方法最近已由首席研究人员的实验室开发和发表。我们的长期目标是利用这些研究提供的信息来使局部金核制剂制备具有最佳的治疗或预防细菌感染的功效。更广泛地说，我们还寻求探索互补和替代医学的主要指导原则之一，即由于协同的相互作用，可以增强多组分疗法的活性。预计被证实为这项研究的一部分的方法对其他研究人员有用，这些研究人员必须考虑在许多植物药的活动中起作用的协同相互作用。