Treatment of cutaneous leishmaniasis using Pentalinon andrieuxii root extract

使用 Pentalinon andrieuxii 根提取物治疗皮肤利什曼病

• 批准号: 7762723
• 负责人: Abhay R Satoskar
• 金额: $ 18.56万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7762723
• 关键词: Biological Assay; Biological Factors; Chemicals; Chronic; Cutaneous; Cutaneous Leishmaniasis; Data; Development; Diffuse Cutaneous Leishmaniasis; Disease; Disease Progression; Drug toxicity; Ear; Exhibits; Foundations; Fractionation; Future; Goals; Growth; Healed; Hexanes; Immune response; In Vitro; Inbred BALB C Mice; Infection; Injection of therapeutic agent; Interleukin-10; Lead; Left; Leishmania; Leishmaniasis; Lesion; Localized Skin Lesion; Mammalian Cell; Measures; Mission; Modeling; Mus; NMR Spectroscopy; National Center for Complementary and Alternative Medicine; Parasites; Plant Roots; Procedures; Production; Publishing; Quality Control; Screening procedure; Site; Skin; Testing; Therapeutic Agents; Time; Tissues; Topical agent; Topical application; Visceral; Visceral Leishmaniasis; analytical method; base; clinical application; comparative efficacy; compliance behavior; cytokine; cytotoxic; ear infection; healing; in vivo; killings; lymph nodes; macrophage; mouse model; novel; obligate intracellular parasite; prevent; product development; public health relevance; tool; two-dimensional

DESCRIPTION (provided by applicant): Leishmania are obligate intracellular parasites that cause a wide range of diseases such as cutaneous, mucocutaneous and visceral leishmaniasis. Over 12 million people currently suffer from these diseases and approximately 2 million are infected annually. Cutaneous leishmaniasis (CL) manifests as localized skin lesions which may heal or lead to significant tissue destruction and disfigurement. There is a clear need for a topical treatment against CL because current therapy involves daily injections of antimonials (GlucantimeTM or PentostamTM) for prolonged periods, which are toxic and have poor patient compliance. In the Yucatan Peninsula, Mayan traditional healers use Pentalinon andrieuxii root for topical treatment of CL, which suggests that P. andrieuxii has a potential for use as a topical agent for the treatment of leishmaniasis. We have found that Pentalinon andrieuxii root hexane extract (PARHE) exhibits potent antileishmanial activity. Our published data indicate that PARHE kills Leishmania in vitro as efficiently as GlucantimeTM. In addition, our new preliminary data suggest that PARHE is effective in restricting parasite growth in the infected skin during L. mexicana infection. PARHE also increases leishmanicidal activity in macrophages and is not toxic to mammalian cells. This project will seek to evaluate the efficacy of PARHE as a topical agent to treat CL using mouse models (Aim 1) and to determine the chemical composition of PARHE for the future development of quality control procedures for the bioactive compound(s) (Aim 2). We hypothesize that PARHE will be an effective topical agent in the treatment of both Old world and New world cutaneous leishmaniasis. Our team is uniquely poised to perform these studies due to the complementary expertise in leishmaniasis (Satoskar), and phytochemistry and natural products development (Kinghorn). The data generated from this project will lay the foundations for a later R01 application focused on a more comprehensive study of PARHE and its active components in local or systemic treatment of the different forms of leishmaniasis, and for determining mechanisms of action of the antileishmanial molecules isolated from PARHE. Our studies are important because they will determine if a local application of PARHE prevents lesion development and/or promotes the cure of CL as well as identify bioactive molecules in PARHE which are important for future clinical applications. PUBLIC HEALTH RELEVANCE: The overall goal of this project is to develop a natural product as a potential topical agent to treat cutaneous leishmaniasis.

描述（由申请人提供）：利什曼尼亚是务必引起多种疾病，例如皮肤，粘膜和内脏利什曼病。目前有超过1200万人患有这些疾病，每年大约有200万人被感染。皮肤利什曼病（CL）表现为局部皮肤病变，可能会愈合或导致严重的组织破坏和毁容。显然需要针对CL的局部治疗，因为当前的治疗涉及每天长时间注射抗微剂（葡萄糖症或pentostamtm），这是有毒且患者依从性较差的时间。在尤卡坦半岛中，玛雅传统治疗师使用Pentalinon Andrieuxii根部对CL进行局部处理，这表明P. andrieuxii有可能用作治疗利什曼病的局部药物。我们发现，Pentalinon Andrieuxii根己烷提取物（Parhe）表现出有效的抗精性活动。我们发表的数据表明，Parhe在体外杀死了利什曼原虫，就像葡萄糖仪一样有效。此外，我们的新初步数据表明，Parhe有效地限制了墨西哥乳杆菌感染期间感染皮肤的寄生虫生长。 Parhe还增加了巨噬细胞中的利什曼杀菌活性，对哺乳动物细胞没有毒性。该项目将旨在评估Parhe作为局部使用者使用小鼠模型治疗CL的功效（AIM 1），并确定Parhe的化学成分以未来开发生物活性化合物的质量控制程序（AIM 2）。我们假设Parhe将是治疗旧世界和新世界皮肤利什曼病的有效主题。由于利什曼病（Satoskar）以及植物化学和天然产品开发（Kinghorn）的补充专业知识（Kinghorn），我们的团队唯一准备进行这些研究。该项目产生的数据将为后来的R01应用程序奠定基础，该应用集中在对Parhe的更全面研究及其在不同形式的利什曼病的局部或系统处理中的积极组成部分，并确定与Parhe隔离的抗精神经会分子的作用机理。我们的研究很重要，因为它们将确定Parhe的局部应用是否可以防止病变的发展和/或促进CL的治疗以及鉴定Parhe中的生物活性分子，这对于将来的临床应用很重要。 公共卫生相关性：该项目的总体目标是开发自然产品作为治疗皮肤利什曼病的潜在局部媒介。

项目成果

Transgenic T cell-specific expression of CXCR3 enhances splenic and hepatic T cell accumulation but does not affect the outcome of visceral leishmaniasis.

• DOI: 10.1016/j.cellimm.2016.08.016
• 发表时间: 2016-11
• 期刊: Cellular immunology
• 影响因子: 4.3
• 作者: Varikuti S;Natarajan G;Oghumu S;Sperling RH;Moretti E;Stock J;Papenfuss TL;Satoskar AR
• 通讯作者: Satoskar AR