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）：利什曼原虫是专性细胞内寄生虫，可引起多种疾病，例如皮肤、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，因为目前的治疗涉及每天长时间注射锑剂（GlucantimeTM 或 PentostamTM），这些药物有毒且患者依从性差。在尤卡坦半岛，玛雅传统治疗师使用 Pentalinon andrieuxii 根局部治疗 CL，这表明 P. andrieuxii 有潜力用作治疗利什曼病的外用药物。我们发现 Pentalinon andrieuxii 根己烷提取物 (PARHE) 具有有效的抗利什曼病活性。我们发表的数据表明 PARHE 在体外杀死利什曼原虫的效率与 GlucantimeTM 一样。此外，我们的新初步数据表明，PARHE 可有效限制墨西哥乳杆菌感染期间受感染皮肤中的寄生虫生长。 PARHE 还可以增加巨噬细胞的杀利什曼活性，并且对哺乳动物细胞无毒。该项目将寻求使用小鼠模型评估 PARHE 作为局部用药治疗 CL 的功效（目标 1），并确定 PARHE 的化学成分，以便未来开发生物活性化合物的质量控制程序（目标 2） ）。我们假设 PARHE 将成为治疗旧世界和新世界皮肤利什曼病的有效外用药物。由于利什曼病 (Satoskar) 以及植物化学和天然产品开发 (Kinghorn) 方面的互补专业知识，我们的团队具有独特的优势来开展这些研究。该项目产生的数据将为以后的 R01 应用奠定基础，该应用侧重于对 PARHE 及其活性成分在不同形式利什曼病的局部或全身治疗中进行更全面的研究，并确定分离的抗利什曼分子的作用机制来自帕赫。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预防病变发展和/或促进 CL 的治愈，并确定 PARHE 中的生物活性分子，这对未来的临床应用很重要。 公共健康相关性：该项目的总体目标是开发一种天然产品作为治疗皮肤利什曼病的潜在外用药物。

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