Beyeryl tribenzoate

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and this study underlines the significance of a small molecule glyceryl tribenzoate (GTB), a FDA approved food additive, in preventing parkinsonian pathologies in MPTP-induced animal models. The study conducted in MPTP-induced mice demonstrated dose-dependent protection of nigral tyrosine hydroxylase (TH) and striatal dopamine level by GTB oral treatment and the optimum dose was found to be 50 mg/kg/d. In the next phase, the study was carried out in MPTP-injected hemiparkinsonian monkeys, which recapitulate better clinical parkinsonian syndromes. GTB inhibited MPTP-driven induction of glial inflammation, which was evidenced by reduced level of GTP-p21Ras and phospho-p65 in SN of monkeys. It led to decreased expression of inflammatory markers such as IL-1β and iNOS. Simultaneously, GTB oral treatment protected nigral TH cells, striatal dopamine, and improved motor behaviour of hemiparkinsonian monkeys. Presence of sodium benzoate, a GTB metabolite and a FDA-approved drug for urea cycle disorders and glycine encephalopathy, in the brain suggests that the neuroprotective effect imparted by GTB might be mediated by sodium benzoate. Although the mechanism of action of GTB is poorly understood, the study sheds light on the therapeutic possibility of a food additive GTB in PD.

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.

Huntington's disease (HD) is a neurodegenerative disorder characterized by accumulation of mutant huntingtin protein and significant loss of neurons in striatum and cortex. Along with motor difficulties, the HD patients also manifest anxiety and loss of cognition. Unfortunately, the clinically approved drugs only offer symptomatic relief and are not free from side effects. This study underlines the importance of glyceryl tribenzoate (GTB), an FDA-approved food flavoring ingredient, in alleviating HD pathology in transgenic N171-82Q mouse model. Oral administration of GTB significantly reduced mutant huntingtin level in striatum, motor cortex as well as hippocampus and increased the integrity of viable neurons. Furthermore, we found the presence of sodium benzoate (NaB), a FDA-approved drug for urea cycle disorders and glycine encephalopathy, in the brain of GTB-fed HD mice. Accordingly, NaB administration also markedly decreased huntingtin level in striatum and cortex. Glial activation is found to coincide with neuronal death in affected regions of HD brains. Interestingly, both GTB and NaB treatment suppressed activation of glial cells and inflammation in the brain. Finally, neuroprotective effect of GTB and NaB resulted in improved motor performance of HD mice. Collectively, these results suggest that GTB and NaB may be repurposed for HD.