The Immunomodulatory Effects of Oral Nanocurcumin in Multiple Sclerosis Patients

Multiple sclerosis is the most common autoimmune disease of the central nervous system, most ranging in age from 40-20 years of age is associated with neurons inflammation and demyelination. Increasing aggressive activities of Th17 and Th1 cells that their function is to secrete proinflammatory cytokines and decreasing the number and activity of regulatory T cells, which normally leads to controlling inflammation, are seen in these patients.Many studies have carried out to assess the prevalence of Tregs and Th17 in autoimmune disorders such as MS. The Treg /Th17 functional balance is necessary for the impediment of autoimmune and inflammatory diseases by preventing harmful injury to the host and increasing effective immune responses. miRNAs have been shown to play a pivotal role in the pathogenesis of various diseases including autoimmune or auto-inflammatory diseases. Curcumin, the active principle constituent of turmeric, is proved to be capable of regulating cellular responses and the growth of different cell types in the immune system such as B cells, T cells, macrophages, dendritic cells and natural killer cells. Curcumin has a combination of activities such as anti-inflammatory, antioxidant, anti-proliferation, anti-invasive, and can used in the treatment of Alzheimer's, Parkinson's, Multiple sclerosis, Cardiovascular disease, Bacterial diseases and Arthritis. The solubility of curcumin in nanomicelles spherical water increases to more than 100 thousand times, which significantly enhances the absorption of curcumin. The present study aimed at investigating the effects of nanocurcumin on the frequency of Treg and Th17 cells, expression levels of their associated transcription factors and cytokines, secretion levels of their associated cytokines and also related miRNAs expression levels in peripheral blood of patients with MS.

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In this study, fresh blood samples were acquired from 50 MS patients introduced by corresponding physician and Neurologist. As the aim of the current study was the assessment of nanocurcumin in MS patients, the peripheral blood collection was collected in two steps. After the first blood collection via venipuncture, 25 patients received nanocurcumin capsules each day and the remaining 25 patients took placebo for 6 months. Accordingly, the second sampling from the mentioned population was collected after 6 months. 9 patients were excluded from the study: 3 did not provide informed consent, 5 lived quite far away from the place in which follow-up examinations were performed, and 1 patient developed cancer. In all cases, 15 ml of blood was utilized for peripheral blood mononuclear cells (PBMC) isolation. PBMC is used to measure the expression levels of miRNA-106b, miRNA-25 and miRNA-326. In this regard, specific kits extracted miRNA from cells is used. Then the version of miRNA using Quantitative Real time polymerase chain reaction(qPCR).Then the frequency of Treg and Th17 cells in peripheral blood of patients will be examined by Flowcytometry and compared to the control group. The expression of key transcription factor (Foxp3) and specific cytokines (TGF-β) related to the Treg cells and key transcription factor (RORγt) and specific cytokines, interleukin-17(IL-17), related to the Th17 are measured by Quantitative Real time PCR. Elisa methos is used to assess the amount of the cytokine TGF-β and IL-17 in cultured cells.

Eligibility Criteria:
Inclusion Criteria:

* Willingness to cooperate
* Aged 18 to 65 years
* The diagnosis of Multiple sclerosis by Neurologist
* Patients in Relapsing Remitting (RRMS)
* Patients with Expanded Disability Status Scale (EDSS) \<5/5.

Exclusion Criteria:

* Use of nutritional supplements and antioxidant and immunosuppressive drugs alpha-lipoic acid a month before the study.
* Pregnancy and lactation
* History of diabetes and other chronic diseases
* History of other autoimmune diseases
* Occurrence of relapses during the study period
* Acceptance rate of less than 70% of supplements
* Unwillingness to continue to cooperate