In spite of extensive research on the pathogenesis of MS, no effective therapy is available to halt this demyelinating disease process. In MS, myelin repair is generally insufficient despite the relative survival of oligodendrocytes within the plaques and the recruitment of oligodendrocyte precursors. Promoting remyelination, therefore, appears to be a crucial therapeutic challenge. While neurotrophins (NGF, NT-3, NT-4/5, and BDNF) and glial cell line-derived neurotrophic factor (GDNF)-related factors (GDNF, neurturin) do not increase myelinogenesis, ciliary neurotrophic factor (CNTF) induces a strong promyelinating effect. Therefore, increasing the level of CNTF in the CNS is an important step in repairing axonal damage in MS. Although gene manipulation and stereotaxic injection of CNTF into the brain are available options, it seems from the therapeutic angle, the best option is to stimulate/induce the production of CNTF within the CNS of patients with MS. Is it really possible? Our exciting preliminary results demonstrate that it is possible by a natural compound. Cinnamon is a natural spice and flavoring material used for centuries throughout the world. We have found that oral feeding of ground cinnamon increases the level of CNTF in the CNS of normal mice and mice with experimental allergic encephalomyelitis (EAE);an animal model of MS. Consistently, cinnamon metabolite sodium benzoate (NaB) also increases the expression of CNTF in astrocytes. Therefore, from the academic angle, we have planned experiments in Specific aim I to investigate molecular mechanisms by which cinnamon metabolite NaB increases CNTF in astrocytes.
Specific aim II has been devoted for therapeutic purposes. Here we would like to delineate the efficacy of orally administered cinnamon in inhibiting the disease process of EAE.
Specific aim III has been enshrined to delineate if cinnamon requires CNTF to inhibit the disease process of EAE. If our study becomes successful, it will describe a novel myelinotrophic activity of cinnamon and ~ 1 teaspoonful of ground cinnamon per day may help MS patients to manage the disease process bringing down the drug cost to <$10 per month for each patient.

Public Health Relevance

In spite of extensive research on the pathogenesis of MS, no effective therapy is available to halt this demyelinating disease process. Studies proposed from various angles in this grant application will delineate the efficacy of orally administered cinnamon in increasing oligodendroglial trophic factor CNTF in the CNS and inhibiting the disease process of EAE, an animal model of MS. If our study becomes successful, ~1 teaspoonful of ground cinnamon per day with tea, milk, cocoa, or honey may help MS patients to manage the disease process.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
5R01AT006681-02
Application #
8270001
Study Section
Special Emphasis Panel (ZRG1-BDCN-N (02))
Program Officer
Pontzer, Carol H
Project Start
2011-06-01
Project End
2016-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
2
Fiscal Year
2012
Total Cost
$371,250
Indirect Cost
$123,750
Name
Rush University Medical Center
Department
Neurosciences
Type
Schools of Medicine
DUNS #
068610245
City
Chicago
State
IL
Country
United States
Zip Code
60612
Mondal, Susanta; Jana, Malabendu; Dasarathi, Sridevi et al. (2018) Aspirin ameliorates experimental autoimmune encephalomyelitis through interleukin-11-mediated protection of regulatory T cells. Sci Signal 11:
Chakrabarti, Sudipta; Jana, Malabendu; Roy, Avik et al. (2018) Upregulation of Suppressor of Cytokine Signaling 3 in Microglia by Cinnamic Acid. Curr Alzheimer Res 15:894-904
Mondal, Susanta; Dasarathi, Sridevi; Pahan, Kalipada (2017) Glyceryl Tribenzoate: A Flavoring Ingredient, Inhibits the Adoptive Transfer of Experimental Allergic Encephalomyelitis via TGF-?: Implications for Multiple Sclerosis Therapy. J Clin Cell Immunol 8:
Modi, Khushbu K; Rangasamy, Suresh B; Dasarathi, Sridevi et al. (2016) Cinnamon Converts Poor Learning Mice to Good Learners: Implications for Memory Improvement. J Neuroimmune Pharmacol 11:693-707
Kundu, Madhuchhanda; Mondal, Susanta; Roy, Avik et al. (2016) Sodium Benzoate, a Food Additive and a Metabolite of Cinnamon, Enriches Regulatory T Cells via STAT6-Mediated Upregulation of TGF-?. J Immunol 197:3099-3110
Ghosh, Arunava; Pahan, Kalipada (2016) PPAR? in lysosomal biogenesis: A perspective. Pharmacol Res 103:144-8
Ghosh, Arunava; Jana, Malabendu; Modi, Khushbu et al. (2015) Activation of peroxisome proliferator-activated receptor ? induces lysosomal biogenesis in brain cells: implications for lysosomal storage disorders. J Biol Chem 290:10309-24
Pahan, Kalipada (2015) Prospects of Cinnamon in Multiple Sclerosis. J Mult Scler (Foster City) 2:1000149
Roy, Avik; Pahan, Kalipada (2015) PPAR? signaling in the hippocampus: crosstalk between fat and memory. J Neuroimmune Pharmacol 10:30-4
Corbett, Grant T; Gonzalez, Frank J; Pahan, Kalipada (2015) Activation of peroxisome proliferator-activated receptor ? stimulates ADAM10-mediated proteolysis of APP. Proc Natl Acad Sci U S A 112:8445-50

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