This is a renewal application aimed at investigating the epigenetic pathways through which botanicals used commonly as CAM, suppress inflammation. During the previous funding cycle, we have made outstanding progress identifying novel cellular and molecular pathways through which botanicals mediate their anti- inflammatory properties. Inflammation can trigger a wide range of diseases including autoimmune, cardiovascular, neurodegenerative, obesity, and certain types of cancer. For this reason, it is not only critical to uncover as-yet-unknown immune mechanisms and mediators of inflammation but also find novel treatment modalities. Because currently there are no medications that can effectively treat chronic inflammation and associated pain without significant side effects, our proposed studies are highly significant. Traditionally, the medicine practiced in India (Ayurveda) and China have used herbal products to treat inflammatory disorders. Also, more than 25% of the pharmaceuticals are derived from plants, which suggests that botanicals offer novel modalities against inflammation. Epigenetic modifications of chromatin and DNA have been shown recently to play a critical role in the regulation in human pathologies, including inflammation. Thus, the concept that botanicals used as CAM may mediate their effects through epigenetic regulation is highly innovative. The primary objective of the Center is to test the overarching hypothesis that botanicals currently used as CAM, regulate the epigenetic signaling pathways through interactions with specific receptors on immune cells to modulate gene expression leading to amelioration of inflammation. This will be tested using four research projects, 1) Identifying epigenetic pathways through which resveratrol (RES) triggers myeloid- derived suppressor cells (MDSCs) in the regulation of neuroinflammation. 2) Epigenetic regulation of Nrf2 signaling pathway in American ginseng (AG)-mediated suppression of inflammation in the colon and colon cancer. 3) Elucidation of the epigenetic mechanisms underlying dietary indole-mediated amelioration of inflammation in the colon specifically addressing how indoles activate AhR to promote Tregs and suppress Th17 cells. 4) Identifying the role of Sparstolonin B (a compound isolated from Sparganium stoloniferum tubers), as a TLR2 and TLR4 antagonist, thereby suppressing inflammation in the liver through epigenetic regulation. The projects are highly integrated and synergistic, all addressing epigenetic pathways so that the data generated from one project will benefit other projects. The projects will use an Administrative Core which will coordinate all activities of the Center and ensure scientific and programmatic progress. All projects will also use an Analytical Core which will perform genome-wide DNA methylation, histone methylation/acetylation, microRNA arrays, immune monitoring, bioinformatics and natural product integrity testing. Together, our CAM Center will identify epigenetic biomarkers and pathways through which botanicals suppress inflammation thereby paving the way for better treatment modality against inflammatory diseases.

Public Health Relevance

Inflammation is considered to be the underlying cause of most clinical disorders for which currently no effective treatment exists. Our goal is to identify the mechanisms through which botanicals suppress inflammation, specifically looking at chemical reactions outside the DNA that can influence the functions of genes and cells.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Research Program Projects (P01)
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Special Emphasis Panel (ZAT1)
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Pontzer, Carol H
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University of South Carolina at Columbia
Schools of Medicine
United States
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Hofseth, Lorne J (2018) Getting rigorous with scientific rigor. Carcinogenesis 39:21-25
Abron, Jessicca D; Singh, Narendra P; Murphy, Angela E et al. (2018) Differential role of CXCR3 in inflammation and colorectal cancer. Oncotarget 9:17928-17936
Bam, Marpe; Yang, Xiaoming; Sen, Souvik et al. (2018) Characterization of Dysregulated miRNA in Peripheral Blood Mononuclear Cells from Ischemic Stroke Patients. Mol Neurobiol 55:1419-1429
Elliott, David M; Singh, Narendra; Nagarkatti, Mitzi et al. (2018) Cannabidiol Attenuates Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis Through Induction of Myeloid-Derived Suppressor Cells. Front Immunol 9:1782
Kenne, Gabriel J; Gummadidala, Phani M; Omebeyinje, Mayomi H et al. (2018) Activation of Aflatoxin Biosynthesis Alleviates Total ROS in Aspergillus parasiticus. Toxins (Basel) 10:
Bader, Jackie E; Enos, Reilly T; Velázquez, Kandy T et al. (2018) Macrophage depletion using clodronate liposomes decreases tumorigenesis and alters gut microbiota in the AOM/DSS mouse model of colon cancer. Am J Physiol Gastrointest Liver Physiol 314:G22-G31
Wirth, Michael D; Sevoyan, Maria; Hofseth, Lorne et al. (2018) The Dietary Inflammatory Index is associated with elevated white blood cell counts in the National Health and Nutrition Examination Survey. Brain Behav Immun 69:296-303
Becker, William; Nagarkatti, Mitzi; Nagarkatti, Prakash S (2018) miR-466a Targeting of TGF-?2 Contributes to FoxP3+ Regulatory T Cell Differentiation in a Murine Model of Allogeneic Transplantation. Front Immunol 9:688
Dopkins, Nicholas; Nagarkatti, Prakash S; Nagarkatti, Mitzi (2018) The role of gut microbiome and associated metabolome in the regulation of neuroinflammation in multiple sclerosis and its implications in attenuating chronic inflammation in other inflammatory and autoimmune disorders. Immunology 154:178-185
Abron, Jessica D; Singh, Narendra P; Mishra, Manoj K et al. (2018) An endogenous aryl hydrocarbon receptor ligand, ITE, induces regulatory T cells and ameliorates experimental colitis. Am J Physiol Gastrointest Liver Physiol 315:G220-G230

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