Immune Modulation of Autoimmunity by Herbal Products

草药产品对自身免疫的免疫调节

• 批准号: 8290064
• 负责人: KAMAL D MOUDGIL
• 金额: $ 36.75万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8290064
• 关键词: Address; Adopted; Adoptive Transfer; Adult; Adverse reactions; Affect; American; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Antibody Formation; Antibody Suppression; Antigens; Antioxidants; Arthritis; Autoimmune Diseases; Autoimmune Responses; Autoimmunity; Botanicals; Celastraceae; Celastrus; Cell Migration Inhibition function; Cells; Centers for Disease Control and Prevention (U.S.); China; Chinese Herbs; Chronic; Clinical; Communities; Complementary and alternative medicine; Consumption; Diabetes Mellitus; Disease; Disease Outcome; Down-Regulation; Drug usage; Enhancing Antibodies; Experimental Models; Family; Folk Remedy; Frequencies; Gastrointestinal Diseases; Generations; Healthcare; Heat shock proteins; Herb; IL2RA gene; Immune; Immune response; Immune system; Immunosuppressive Agents; In Vitro; Infiltration; Inflammation Mediators; Inflammatory; Insulin-Dependent Diabetes Mellitus; Label; Lupus; Lymphocyte; Malignant Neoplasms; Mediating; Medicinal Herbs; Mind; Modality; Modeling; Mononuclear; Multiple Sclerosis; National Health Interview Survey; Nitric Oxide; Organ; Patients; Pattern; Pharmaceutical Preparations; Plant Roots; Plants; Process; Production; Property; Province; Publishing; Rattus; Regulatory T-Lymphocyte; Relative (related person); Rheumatism; Rheumatoid Arthritis; Serum; Severities; Stroke; Surveys; Systemic Lupus Erythematosus; T-Lymphocyte; T-Lymphocyte Epitopes; Testing; Therapeutic; Therapeutic Agents; Therapeutic Effect; Tissues; Toxic effect; Water; Western World; alternative treatment; base; cost; cytokine; design; feeding; human NOS2A protein; immunoregulation; in vivo; migration; mycobacterial; public health relevance; research study; response; stem; trafficking

DESCRIPTION (provided by applicant): At least 36 percent of adult Americans adopted some form of complementary and alternative medicine (CAM) therapy for their healthcare needs annually as surveyed 5 years ago (National Interview Health Survey of 2002, CDC). Among CAM modalities, the use of naturally grown plant products as efficacious therapeutic entities as well as the relative lack of toxicity of herbs compared to conventionally used drugs has popularized the consumption of botanical formulas in the western world. Despite the extensive use of medicinal herbs, the mechanisms of action remain unclear for most of them. Our preliminary study using an experimental model of autoimmunity has revealed that the Chinese herb Celastrus suppresses clinical disease and induces significant changes in antigen-specific immune response (e.g., deviation of the cytokine response from pro-inflammatory to anti-inflammatory type, and increased production of antigenspecific antibodies). In this study, we have proposed experiments to test the in-depth mechanisms of Celastrus-induced immune modulation operative via the CD4+CD25+ T regulatory cells (Treg), the in vivo trafficking of lymphocytes into the target organ, the protective antibodies, and the inflammatory mediators. In this respect, our proposal is an excellent match with the objectives of RFA-AT-08-003. Aim 1. To study the suppressive function of CD4+CD25+T cells that leads to the downregulation of the disease process in Celastrus-fed rats. Aim 2. To examine the mechanisms by which Celastrus reduces the migration of potentially pathogenic T cells into the target organ. Aim 3. To determine how enhanced antibody response to the disease-related antigen leads to suppression of the autoimmune response. Aim 4. To test for the Celastrus-induced modulation of inflammatory mediators in the target tissue. Although this proposal involves one CAM modality (a Chinese herb) and one experimental model of autoimmunity, we believe that the basic mechanistic principles elucidated in our study would also be applicable in part to other CAM modalities as well as other models of autoimmunity. Public Health Relevance: Natural plant products are increasingly being used by patients with a variety of autoimmune diseases, such as diabetes, multiple sclerosis, arthritis and lupus. However, the mechanisms of action of many of these products are not defined. We propose to study the immune system related mechanisms by which Celastrus, a Chinese herb, mediates its beneficial effects against autoimmunity. We will conduct these studies in an experimental model of autoimmunity. The results of our study would help developing rationally designed therapeutic approaches for autoimmunity using botanical products.

描述（由申请人提供）：5年前进行的调查，至少有36％的成年美国人每年对其医疗保健需求采用某种形式的补充和替代医学（CAM）疗法（2002年国家访谈健康调查，CDC）。在CAM模式中，与传统使用的药物相比，使用自然种植的植物产品作为有效的治疗实体以及相对缺乏草药的毒性，这普及了西方世界中植物配方剂的消费。尽管大量使用药草，但大多数情况下的作用机制仍然不清楚。我们使用自身免疫性实验模型的初步研究表明，中草药celastrus抑制了临床疾病，并引起抗原特异性免疫反应的显着变化（例如，促炎对抗炎类型的细胞因子反应的偏差，抗炎类型的抗原类型，以及抗原特异性抗体的产生）。在这项研究中，我们提出了通过CD4+ CD25+ T调节细胞（TREG）（Treg），淋巴细胞在靶器官的体内运输，保护性抗体和炎症性媒介物的体内运输中，通过CD4+ CD25+ T调节细胞（Treg）测试了Celastrus诱导的免疫调节作用的深入机理。在这方面，我们的建议与RFA-AT-08-003的目标相匹配。目的1。研究CD4+CD25+T细胞的抑制功能，从而导致celastrus喂养大鼠疾病过程的下调。目的2。检查celastrus降低潜在致病T细胞迁移到靶器官的机制。目的3。确定抗体对疾病相关抗原的增强反应如何导致自身免疫反应的抑制。 AIM 4。测试目标组织中Celastrus诱导的炎症介质的调节。尽管该提案涉及一种CAM模式（一种中文草药）和一种自身免疫性的实验模型，但我们认为，在我们的研究中阐明的基本机械原理也将部分适用于其他CAM模式以及其他自身免疫性的模型。 公共卫生相关性：各种自身免疫性疾病的患者（例如糖尿病，多发性硬化症，关节炎和狼疮）越来越多地使用天然植物产品。但是，许多这些产品的作用机制尚未定义。我们建议研究中国草药Celastrus介导其针对自身免疫性的有益作用，以研究免疫系统相关的机制。我们将在自身免疫的实验模型中进行这些研究。我们的研究结果将有助于使用植物产品开发合理设计的自身免疫治疗方法。

项目成果

Microarray-based gene expression profiling reveals the mediators and pathways involved in the anti-arthritic activity of Celastrus-derived Celastrol.

• DOI: 10.1016/j.intimp.2012.05.015
• 发表时间: 2012-08
• 期刊: International immunopharmacology
• 影响因子: 5.6
• 作者: Yu H;Venkatesha SH;Moudgil KD
• 通讯作者: Moudgil KD

Temporal cytokine expression and the target organ attributes unravel novel aspects of autoimmune arthritis.

颞细胞因子表达和靶器官属性揭示了自身免疫性关节炎的新方面。

• 发表时间: 2013
• 期刊: The Indian journal of medical research
• 作者: Astry,Brian;Venkatesha,ShivaprasadH;Moudgil,KamalD
• 通讯作者: Moudgil,KamalD

Heat-shock proteins in autoimmunity.

• DOI: 10.1155/2013/621417
• 发表时间: 2013
• 期刊: Autoimmune diseases
• 影响因子: 4
• 作者: Moudgil KD;Thompson SJ;Geraci F;De Paepe B;Shoenfeld Y
• 通讯作者: Shoenfeld Y

Suppression of autoimmune arthritis by Celastrus-derived Celastrol through modulation of pro-inflammatory chemokines.

• DOI: 10.1016/j.bmc.2012.06.050
• 发表时间: 2012-09-01
• 期刊: BIOORGANIC & MEDICINAL CHEMISTRY
• 影响因子: 3.5
• 作者: Venkatesha, Shivaprasad H.;Astry, Brian;Nanjundaiah, Siddaraju M.;Yu, Hua;Moudgil, Kamal D.
• 通讯作者: Moudgil, Kamal D.

Modulation of autoimmune arthritis by environmental 'hygiene' and commensal microbiota.

• DOI: 10.1016/j.cellimm.2018.12.005
• 发表时间: 2019-05
• 期刊: Cellular immunology
• 影响因子: 4.3
• 作者: Langan D;Kim EY;Moudgil KD
• 通讯作者: Moudgil KD