Prospects of Cinnamon in Multiple Sclerosis.

Although the central nervous system (CNS) is separated from the immune system by blood-brain barrier and traditionally considered “immune priviledged”, our immune cells are capable of targeting the brain, leading to the development of CNS autoimmune disorders. Multiple sclerosis (MS) is one such autoimmune disorder of the CNS in which myelin components are particularly targeted by the immune system resulting in demyelination of axons and associated debilitating symptoms [1–3]. In spite of intense investigations, no effective therapy is available for this disease. Therefore, a safe and effective therapeutic option is necessary for MS. Fortunately, we have been endowed with enormous natural remedies to take care our health issues. For example, cinnamon, the brown bark of cinnamon tree, that has already been being used for centuries throughout the world as spice or flavoring agent. Furthermore, medieval physicians used cinnamon for medical purposes to treat a variety of disorders including arthritis, coughing, hoarseness, sore throats, etc. Recent studies are indicating that this natural product may be helpful for MS [4–6]. Although the etiology of MS is poorly understood, it is becoming clear that widespread inflammation, loss of regulatory T cells (Tregs), hyperactivity of autoimmune Th1 and Th17 cells, breakdown of blood-brain barrier (BBB) and blood-spinal cord barrier (BSB), and loss of neuroprotective molecules in the CNS are critical for the manifestation of demyelinating pathology in MS [1–3]. Interestingly, cinnamon treatment is capable of modifying these pathological features in mice with experimental allergic encephalomyelitis (EAE), an animal model of MS [4,6]. Types of cinnamon Cinnamonum cassia (Chinese cinnamon) and Cinnamonum verum or Cinnamonum zylencum (Ceylon cinnamon) are two readily available brands of cinnamon in the world. Although both types of cinnamon contain cinnamaldehyde as the major compound, we have seen the presence of coumarin, a hepatotoxic molecule, in Cinnamonum cassia, but not Cinnamonum verum. Furthermore, Cinnamonum cassia contain more styrene, benzene, 1,1′-(2-butene-1,4-diyl)bis-, benzene, 1,1′-(1,2-cyclobutanediyl)bis-, palmitic acid, stearic acid, 4-phenylbutyl chloride, and (2,3-diphenylcyclopropyl) methyl phenyl sulfoxide, which are present in Cinnamonum verum in negligible amounts [7]. Therefore, for the treatment of mice with EAE, we used Cinnamonum verum. Upon ingestion, cinnamaldehyde present in Cinnamon is converted into cinnamic acid by oxidation. In the liver, this cinnamic acid is β-oxidized to benzoate that exists as sodium benzoate (NaB) or benzoyl-CoA. A minor amount of NaB, a direct metabolite of cinnamic acid, is also excreted in the urine of humans. Recently, we have demonstrated that oral administration of ground Cinnamonum verum increases the level of NaB in serum and brain of mice [7]. NaB is of medical importance as being a component of Ucephan, a FDA-approved drug, it is used in the treatment for hepatic metabolic defects associated with hyperammonemia such as urea cycle disorder in children [8,9]. NaB is also a widely used preservative in broad range of foods and cosmetic products. It has been reported that 2% solution of NaB in drinking water is safe for lifelong treatment in mice without any noticeable side effects [10].