Cinnamein Inhibits the Induction of Nitric Oxide and Proinflammatory Cytokines in Macrophages, Microglia and Astrocytes.

Chronic inflammation driven by proinflammatory cytokines (TNFα, IL-1ß, IL-6, etc.), and nitric oxide (NO) plays an important role in the pathogenesis of several autoimmune, inflammatory as well as neurodegenerative disorders like rheumatoid arthritis, multiple sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, etc. Therefore, identification of nontoxic anti-inflammatory drugs may be beneficial for these autoimmune, inflammatory and neurodegenerative disorders. Cinnamein, an ester derivative of cinnamic acid and benzyl alcohol, is used as a flavoring agent and for its antifungal and antibacterial properties. This study underlines the importance of cinnamein in inhibiting the induction of proinflammatory molecules in RAW 264.7 macrophages and primary mouse microglia and astrocytes. Stimulation of RAW 264.7 macrophages with lipopolysaccharide (LPS) and interferon γ (IFNγ) led to marked production of NO. However, cinnamein pretreatment significantly inhibited LPS- and IFNγ-induced production of NO in RAW 264.7 macrophages. Cinnamein also reduced the mRNA expression of inducible nitric oxide synthase (iNOS) and TNFα in RAW cells. Accordingly, LPS and viral double-stranded RNA mimic polyinosinic: polycytidylic acid (polyIC) stimulated the production of TNFα, IL-1ß and IL-6 in primary mouse microglia, which was inhibited by cinnamein pretreatment. Similarly, cinnamein also inhibited polyIC-induced production of TNFα and IL-6 in primary mouse astrocytes. These results suggest that cinnamein may be used to control inflammation in different autoimmune, inflammatory and neurodegenerative disorders.

Glyceryl tribenzoate: A food additive with unique properties to be a substitute for cinnamon.

Cinnamon is a regularly used natural seasoning and flavoring material throughout the world for eras. Recent laboratory studies have demonstrated that oral cinnamon may be beneficial for different neuroinflammatory and neurodegenerative disorders such as multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD), and Lewy body diseases (LBD). However, cinnamon's certain limitations (e.g. unavailability of true Ceylon cinnamon throughout the world, impurities in ground cinnamon, etc.) have initiated an interest among researchers to find an alternate of cinnamon that can potentially deliver the same efficacy in the diseases mentioned above. Glyceryl tribenzoate (GTB) is a U.S. Food and Drug Administration (FDA)-approved flavoring ingredient that is used in food and food packaging industries. It has been found that similar to cinnamon, oral GTB is capable of upregulating regulatory T cells and suppressing the autoimmune disease process of experimental autoimmune encephalomyelitis, an animal model of MS. Moreover, both GTB and cinnamon metabolite sodium benzoate (NaB) have the potency to attenuate neurodegenerative pathology in a mouse model of Huntington disease (HD). Here, we have also demonstrated anti-inflammatory property of GTB in astrocytes and macrophages, a property that is also seen with cinnamon and its metabolite sodium benzoate (NaB). Therefore, here, we have made a sincere attempt to discuss the similarities and dissimilarities between cinnamon and GTB with a focus whether GTB has the potential to be considered as a substitute of cinnamon for neuroinflammatory and neurodegenerative disorders.

Can cinnamon spice down autoimmune diseases?

Autoimmune diseases are one of the dreadful group of human diseases that have always been of keen interest to researchers. Due to complex and broad-spectrum nature, scientists are not yet able to pinpoint the pathogenesis of and delineate effective therapy against this group of diseases. However, it is becoming clear that a decrease in number and function of T regulatory cells (Treg), an increase in autoreactive Th1/Th17 cells and associated immunomodulation and inflammation participate in the pathogenesis of many autoimmune diseases. Cinnamon (Cinnamonum verum or Cinnamonum cassia) is a widely used natural spice and flavoring ingredient and its metabolite sodium benzoate (NaB) is a food-additive and FDA-approved drug against nonketotic hyperglycinemia (NKH) and urea cycle disorders (UCD). Recent studies indicate that cinnamon either in powder or extract form and NaB are capable of modulating different autoimmune pathways as well as protecting animals from different autoimmune disorders. Here, we have made an honest attempt to delineate such pieces of evidence with available anti-autoimmune mechanisms and analyze whether cinnamon supplements could be used to control the fury of autoimmune disorders.

Mode of Action of Aspirin in Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is a chronic and debilitating autoimmune disorder of the central nervous system in which the autoimmune T cells destroy myelin, thus causing lesion, damage, and neuronal dysfunction. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is particularly useful for testing new therapeutic approaches against MS. Aspirin (acetyl salicylic acid) is one of the oldest and widely used medicines in the world, and recently it has been shown that low-dose aspirin is capable of suppressing the disease process of EAE in mice. One of the root causes of this autoimmune disease process is the decrease and/or suppression of Foxp3-expressing anti-autoimmune regulatory T cells (Tregs) and associated increase in autoimmune T-helper 1 (Th1) and Th17 cells. Aspirin upregulates Tregs and decreases Th1 and Th17 responses. Accordingly, the suppression of Tregs abrogates the protective effect of aspirin on EAE, indicating that aspirin protects EAE via Tregs. While there are several mechanisms for the maintenance of Tregs under immune insults, aspirin increases the level of interleukin-11 (IL-11), an immunomodulatory cytokine, and IL-11 alone is sufficient to protect Tregs. Being a multifunctional molecule, aspirin stimulates the activation of cAMP-response element-binding (CREB) to promote the recruitment of CREB to the IL-11 gene promoter and stimulate the transcription of IL-11 in splenocytes. Therefore, it appears that low-dose aspirin protects EAE via CREB-mediated stimulation of IL-11-Treg pathway and that aspirin may have therapeutic importance in MS.