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.

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 approches for autoimmunity using botanical products.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
5R01AT004321-04
Application #
8290064
Study Section
Special Emphasis Panel (ZAT1-SM (13))
Program Officer
Pontzer, Carol H
Project Start
2009-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$367,538
Indirect Cost
$122,513
Name
University of Maryland Baltimore
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Astry, Brian; Venkatesha, Shivaprasad H; Moudgil, Kamal D (2015) Involvement of the IL-23/IL-17 axis and the Th17/Treg balance in the pathogenesis and control of autoimmune arthritis. Cytokine 74:54-61
Venkatesha, Shivaprasad H; Dudics, Steven; Acharya, Bodhraj et al. (2015) Cytokine-modulating strategies and newer cytokine targets for arthritis therapy. Int J Mol Sci 16:887-906
Astry, Brian; Venkatesha, Shivaprasad H; Laurence, Arian et al. (2015) Celastrol, a Chinese herbal compound, controls autoimmune inflammation by altering the balance of pathogenic and regulatory T cells in the target organ. Clin Immunol 157:228-38
Moudgil, Kamal D (2015) Interplay among cytokines and T cell subsets in the progression and control of immune-mediated diseases. Cytokine 74:1-4
Tong, Li; Nanjundaiah, Siddaraju M; Venkatesha, Shivaprasad H et al. (2014) Pristimerin, a naturally occurring triterpenoid, protects against autoimmune arthritis by modulating the cellular and soluble immune mediators of inflammation and tissue damage. Clin Immunol 155:220-30
Moudgil, Kamal D; Berman, Brian M (2014) Traditional Chinese medicine: potential for clinical treatment of rheumatoid arthritis. Expert Rev Clin Immunol 10:819-22
Nanjundaiah, Siddaraju M; Astry, Brian; Moudgil, Kamal D (2013) Mediators of inflammation-induced bone damage in arthritis and their control by herbal products. Evid Based Complement Alternat Med 2013:518094
Yu, Hua; Lu, Changwan; Tan, Ming T et al. (2013) Comparative antigen-induced gene expression profiles unveil novel aspects of susceptibility/resistance to adjuvant arthritis in rats. Mol Immunol 56:531-9
Nanjundaiah, S M; Stains, J P; Moudgil, K D (2013) Kinetics and interplay of mediators of inflammation-induced bone damage in the course of adjuvant arthritis. Int J Immunopathol Pharmacol 26:37-48
Astry, Brian; Venkatesha, Shivaprasad H; Moudgil, Kamal D (2013) Temporal cytokine expression and the target organ attributes unravel novel aspects of autoimmune arthritis. Indian J Med Res 138:717-31

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