Cinnamon Ameliorates Experimental Allergic Encephalomyelitis in Mice via Regulatory T Cells: Implications for Multiple Sclerosis Therapy

Mondal, Sourav; Pahan, Kalipada

doi:10.1371/journal.pone.0116566

Cited by 53 publications

(77 citation statements)

References 45 publications

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“…It is also widely used as a preservative in broad range of foods and cosmetic products (Nair, 2001). We have seen that cinnamon and NaB modify T cells and protect mice from experimental allergic encephalomyelitis, an animal model of multiple sclerosis (Brahmachari and Pahan, 2007; Mondal and Pahan, 2015; Pahan, 2015). Cinnamon and NaB also upregulate neuroprotective molecules (Parkin and DJ-1) and protect dopaminergic neurons in MPTP mouse model of Parkinson’s disease (Khasnavis and Pahan, 2012, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…While NaB and NaFO were solubilized in water, cinnamon ( Cinnamonum verum ) powder was mixed in 0.5% methylcellulose (MC). Mice were gavaged 100 μL cinnamon-mixed MC and 100 μL NaB- and NaFO-mixed water once daily using gavage needle as described (Jana et al, 2013; Khasnavis and Pahan, 2014; Mondal and Pahan, 2014; Modi et al, 2015). Another group of control mice also received only MC as vehicle.…”

Section: Methodsmentioning

confidence: 99%

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Cinnamon Converts Poor Learning Mice to Good Learners: Implications for Memory Improvement

Modi

Rangasamy

Dasarathi

et al. 2016

J Neuroimmune Pharmacol

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This study underlines the importance of cinnamon, a commonly used natural spice and flavoring material, and its metabolite sodium benzoate (NaB) in converting poor learning mice to good learning ones. NaB, but not sodium formate, was found to upregulate plasticity-related molecules, stimulate NMDA- and AMPA-sensitive calcium influx and increase of spine density in cultured hippocampal neurons. NaB induced the activation of CREB in hippocampal neurons via protein kinase A (PKA), which was responsible for the upregulation of plasticity-related molecules. Finally, spatial memory consolidation-induced activation of CREB and expression of different plasticity-related molecules were less in the hippocampus of poor learning mice as compared to good learning ones. However, oral treatment of cinnamon and NaB increased spatial memory consolidation-induced activation of CREB and expression of plasticity-related molecules in the hippocampus of poor-learning mice and converted poor learners into good learners. These results describe a novel property of cinnamon in switching poor learners to good learners via stimulating hippocampal plasticity.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Cinnamon Converts Poor Learning Mice to Good Learners: Implications for Memory Improvement

Modi

Rangasamy

Dasarathi

et al. 2016

J Neuroimmune Pharmacol

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“…Female Tg mice (4–5 weeks old) were immunized with 10 μg of PLP139–151 in M. tuberculosis in IFA as described (19). …”

Section: Methodsmentioning

confidence: 99%

Sodium Benzoate, a Food Additive and a Metabolite of Cinnamon, Enriches Regulatory T Cells via STAT6-Mediated Upregulation of TGF-β

Kundu

Mondal

Roy

et al. 2016

The Journal of Immunology

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Upregulation and/or maintenance of regulatory T cells (Tregs) during autoimmune insults may have therapeutic efficacy in autoimmune diseases. Earlier we have reported that sodium benzoate (NaB), a metabolite of cinnamon and a FDA-approved drug against urea cycle disorders, upregulates Tregs and protects mice from experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis. However, mechanisms by which NaB increases Tregs are poorly understood. Because transforming growth factor beta (TGFβ) is an important inducer of Tregs, we examined the effect of NaB on the status of TGF-β. Here, we demonstrated that NaB induced the expression of TGFβ mRNA and protein in normal as well as proteolipid protein-primed splenocytes. Presence of a consensus STAT6-binding site in the promoter of TGFβ gene, activation of STAT6 in splenocytes by NaB, recruitment of STAT6 to the TGFβ promoter by NaB, and abrogation of NaB-induced expression of TGFβ in splenocytes by siRNA knockdown of STAT6 suggest that NaB induces the expression of TGFβ via activation of STAT6. Furthermore, we demonstrated that blocking of TGFβ by neutralizing antibodies abrogated NaB-mediated protection of Tregs and EAE. These studies identify a new function of NaB in upregulating TGFβ via activation of STAT6, which may be beneficial in MS patients.

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“…Inflammation was determined using the following scale; 0 ¼ No inflammation; 1 ¼ small number of inflammatory cells; 2 ¼ numerous infiltrating cells; and 3 ¼ widespread infiltration. Demyelination was scored as; 0 ¼ normal white matter; 1 ¼ rare foci; 2 ¼ a few areas of demyelination; and 3 ¼ large areas of demyelination (Soellner et al 2013;Mondal & Pahan 2015). Six serial sections of spinal cord/mouse were scored.…”

Section: Histologic Analysismentioning

confidence: 99%

St. John’s wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells

Nosratabadi

Rastin

Sankian

et al. 2015

Journal of Immunotoxicology

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Multiple sclerosis (MS) is a central nervous system disorder mainly characterized by inflammation, demyelination and axonal injury. Anti-inflammatory agents can be used to ameliorate the disease process. Hypericum perforatum L or St. John's wort is widely used as an anti-depressant and antiinflammatory remedy in traditional and herbal medicine. Based on St. John's wort properties, the therapeutic potentials of an H. perforatum extract (HPE) and a single component, hyperforin were evaluated for effectiveness against MOG 35-55 -induced experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Female C57BL/6 mice were immunized with specific antigen MOG 35-55 and then administered different doses of hyperforin or HPE postimmunization. Clinical symptoms/other relevant parameters were assessed daily. Histological analysis of the spinal cord was performed. T-cell proliferative activity was also evaluated using a BrdU assay. The effect of hyperforin on regulatory T-cells (T reg cells) was assessed using flow cytometry. The results indicate hyperforin and HPE reduced the incidence and severity of EAE, an outcome that closely correlated with an inhibition of pathological features (leukocyte infiltration and demyelination) and antigen-specific T-cell proliferation. The study also showed that hyperforin caused increased T reg cell levels in the spleen. These results indicated that hyperforin and HPE could attenuate EAE autoimmune responses by inhibiting immune cell infiltration and expansion of T reg cell and could eventually be considered as a potential candidate for use in the treatment of MS. ARTICLE HISTORY

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Cinnamon Ameliorates Experimental Allergic Encephalomyelitis in Mice via Regulatory T Cells: Implications for Multiple Sclerosis Therapy

Cited by 53 publications

References 45 publications

Cinnamon Converts Poor Learning Mice to Good Learners: Implications for Memory Improvement

Cinnamon Converts Poor Learning Mice to Good Learners: Implications for Memory Improvement

Sodium Benzoate, a Food Additive and a Metabolite of Cinnamon, Enriches Regulatory T Cells via STAT6-Mediated Upregulation of TGF-β

St. John’s wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells

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