Glyceryl Tribenzoate: A Food Additive with Unique Properties to Be a Substitute for Cinnamon

Cinnamon is a regularly used natural seasoning and flavouring 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.

Download Full-text

A predictable sequential determinant spreading cascade invariably accompanies progression of experimental autoimmune encephalomyelitis: a basis for peptide-specific therapy after onset of clinical disease.

Journal of Experimental Medicine ◽

10.1084/jem.183.4.1777 ◽

1996 ◽

Vol 183 (4) ◽

pp. 1777-1788 ◽

Cited By ~ 200

Author(s):

M Yu ◽

J M Johnson ◽

V K Tuohy

Keyword(s):

Autoimmune Disease ◽

Experimental Autoimmune Encephalomyelitis ◽

Disease Process ◽

Proteolipid Protein ◽

Autoimmune Encephalomyelitis ◽

Course Of Disease ◽

Invariant Relationship ◽

Specific Tolerance ◽

Myelin Proteolipid ◽

Experimental Autoimmune

The development of autoimmune disease is accompanied by the acquired recognition of new self-determinants, a process commonly referred to as determinant spreading. In this study, we addressed the question of whether determinant spreading is pathogenic for progression of chronic-relapsing experimental autoimmune encephalomyelitis (EAE), a disease with many similarities to multiple sclerosis (MS). Our approach involved a systematic epitope mapping of responses to myelin proteolipid protein (PLP) as well as assaying responses to known encephalitogenic determinants of myelin basic protein (MBP 87-89) and myelin oligodendrocyte glycoprotein (MOG 92-106) at various times after induction of EAE in (SWR X SJL)F1 mice immunized with PLP 139-151. We found that the order in which new determinants are recognized during the course of disease follows a predictable sequential pattern. At monthly intervals after immunization with p139-151, responses to PLP 249-273, MBP 87-99, and PLP 137-198 were sequentially accumulated in al mice examined. Three lines of evidence showed that determinant spreading is pathogenic for disease progression: (a) spreading determinants mediate passive transfer of acute EAE in naive (SWR X SJL)F1 recipients; (b) an invariant relationship exists between the development of relapse/progression and the spreading of recognition to new immunodominant encephalitogenic determinants; and (c) after EAE onset, the induction of peptide-specific tolerance to spreading but not to nonspreading encephalitogenic determinants prevents subsequent progression of EAE. Thus, the predictability of acquired self-determinant recognition provides a basis for sequential determinant-specific therapeutic intervention after onset of the autoimmune disease process.

Download Full-text

Neural stem cells derived from primitive mesenchymal stem cells reversed disease symptoms and promoted neurogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02563-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Christina Brown ◽

Christina McKee ◽

Sophia Halassy ◽

Suleiman Kojan ◽

Doug L. Feinstein ◽

...

Keyword(s):

Multiple Sclerosis ◽

Stem Cells ◽

Flow Cytometry ◽

Mesenchymal Stem Cells ◽

Inflammatory Response ◽

Mouse Model ◽

Disease Process ◽

Blue Staining ◽

Autoimmune Encephalomyelitis ◽

Experimental Autoimmune

Abstract Background Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). MS affects millions of people and causes a great economic and societal burden. There is no cure for MS. We used a novel approach to investigate the therapeutic potential of neural stem cells (NSCs) derived from human primitive mesenchymal stem cells (MSCs) in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Methods MSCs were differentiated into NSCs, labeled with PKH26, and injected into the tail vein of EAE mice. Neurobehavioral changes in the mice assessed the effect of transplanted cells on the disease process. The animals were sacrificed two weeks following cell transplantation to collect blood, lymphatic, and CNS tissues for analysis. Transplanted cells were tracked in various tissues by flow cytometry. Immune infiltrates were determined and characterized by H&E and immunohistochemical staining, respectively. Levels of immune regulatory cells, Treg and Th17, were analyzed by flow cytometry. Myelination was determined by Luxol fast blue staining and immunostaining. In vivo fate of transplanted cells and expression of inflammation, astrogliosis, myelination, neural, neuroprotection, and neurogenesis markers were investigated by using immunohistochemical and qRT-PCR analysis. Results MSC-derived NSCs expressed specific neural markers, NESTIN, TUJ1, VIMENTIN, and PAX6. NSCs improved EAE symptoms more than MSCs when transplanted in EAE mice. Post-transplantation analyses also showed homing of MSCs and NSCs into the CNS with concomitant induction of an anti-inflammatory response, resulting in reducing immune infiltrates. NSCs also modulated Treg and Th17 cell levels in EAE mice comparable to healthy controls. Luxol fast blue staining showed significant improvement in myelination in treated mice. Further analysis showed that NSCs upregulated genes involved in myelination and neuroprotection but downregulated inflammatory and astrogliosis genes more significantly than MSCs. Importantly, NSCs differentiated into neural derivatives and promoted neurogenesis, possibly by modulating BDNF and FGF signaling pathways. Conclusions NSC transplantation reversed the disease process by inducing an anti-inflammatory response and promoting myelination, neuroprotection, and neurogenesis in EAE disease animals. These promising results provide a basis for clinical studies to treat MS using NSCs derived from primitive MSCs.

Download Full-text

Differential permeability of the BBB in acute EAE: enhanced transport of TNT-alpha

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.271.4.e636 ◽

1996 ◽

Vol 271 (4) ◽

pp. E636-E642 ◽

Cited By ~ 12

Author(s):

W. Pan ◽

W. A. Banks ◽

M. K. Kennedy ◽

E. G. Gutierrez ◽

A. J. Kastin

Keyword(s):

Disease Process ◽

Transport Processes ◽

Transport Systems ◽

Tnf Alpha ◽

Autoimmune Encephalomyelitis ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Differential Permeability ◽

Necrosis Factor ◽

Experimental Autoimmune

Impairment of the blood-brain barrier (BBB) in experimental autoimmune encephalomyelitis (EAE) has been frequently attributed to disruption, without much consideration of saturable transport processes. In mice with EAE, we studied the permeability of the BBB to radioactively labeled albumin and sucrose, markers of BBB disruption, and tumor necrosis factor-alpha (TNF-alpha), a cytokine transported across the BBB by a saturable system and thought to play a role in the pathogenesis of EAE. Permeation of the BBB was increased to all three substances during the acutely ill stage, was greatest in the lumbar spine, and returned to normal with recovery. The change in BBB permeability to sucrose was greater than to the larger albumin and is consistent with a partial disruption of the BBB. The enhanced permeability to TNF-alpha was comparable to that for sucrose, even though TNF-alpha is similar in size to albumin. This paradoxically high uptake of TNF-alpha could be explained by an enhancement of its endogenous saturable transport system. Thus the changes in BBB function during EAE extend beyond disruption to include changes in the saturable transport systems for substances involved in the disease process.

Download Full-text

Macrophage brain infiltration in experimental autoimmune encephalomyelitis is not completely compromised by suppressed T-cell invasion: in vivo magnetic resonance imaging illustration in effective anti-VLA-4 antibody treatment

Multiple Sclerosis Journal ◽

10.1191/1352458504ms1090oa ◽

2004 ◽

Vol 10 (5) ◽

pp. 540-548 ◽

Cited By ~ 32

Author(s):

Mathilde SA Deloire ◽

Tarik Touil ◽

Bruno Brochet ◽

Vincent Dousset ◽

Jean-Marie Caillé ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

T Cells ◽

T Cell ◽

Magnetic Resonance ◽

Experimental Autoimmune Encephalomyelitis ◽

Disease Process ◽

Resonance Imaging ◽

Autoimmune Encephalomyelitis ◽

Antibody Treatment ◽

Experimental Autoimmune

Large inflammatory infiltrates of T cells, macrophages and B cells in the central nervous system (CNS) contribute to the pathogenesis of multiple sclerosis (MS). The passage of T cells through the blood-brain barrier can be suppressed with antibodies directed against alpha-4 integrins (VLA-4) that mediate T-cell adherence. This treatment, in phase III of clinical trial evaluation, reduces lesion development in MS patients. In the ongoing inflammatory disease process the consequences of T-cell inhibitory anti-VLA-4 antibodies on inflammatory compounds are still poorly investigated. We show that anti-VLA-4 antibody treatment during the late preclinical phase of the acute experimental autoimmune encephalomyelitis (EAE) MS rat model interrupts T-cell egress out of the vascular compartment and suppresses clinical disease and histological alterations but macrophage recruitment in the CNS is not fully compromised. Among the treated EAE animals not developing disease, none presented foci of T-cell infiltration in CNS. However, in 75% of the treated EAE rats monocyte ingress in CNS was observedin vivo by magnetic resonance imaging with the ultrasmall superparamagnetic iron oxide contrast agent. Our data shed new light on the role of remaining macrophage brain infiltration in an induced but interrupted T-cell-mediated EAE disease process.

Download Full-text

Histopathological observations of recurrent experimental autoimmune encephalomyelitis (rEAE) in female Lewis rats

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159151 ◽

1990 ◽

Vol 48 (3) ◽

pp. 320-321

Author(s):

J. E. Aschenbrenner ◽

F. L. Jackson ◽

E. L. Orr ◽

I. F. Chang ◽

L. X. Oakford

Keyword(s):

Spinal Cord ◽

Clinical Symptoms ◽

Disease Process ◽

Recovery Phase ◽

Spinal Cord Tissue ◽

Initial Examination ◽

Autoimmune Encephalomyelitis ◽

Lewis Rats ◽

Transmission Electron ◽

Experimental Autoimmune

Experimental autoimmune enchephalomyelltis (EAE) is a disease which can be induced in Lewis rats by exposure of the animal to a source of myelin in the presence of adjuvant. Similar symptoms and histopathology are observed In people with multiple sclerosis (MS) leading to the widespread use of EAE as an animal model for MS (1). Induction of EAE in the male Lewis rat results In a monophasic disease characterized by a single severe occurrence of symptoms followed by spontaneous recovery. Female Lewis rats when exposed to identical stimuli will develop a recurrent form of the disease (rEAE) characterized by a temporally consistent, spontaneous secondary occurrence of clinical symptoms(2), which more closely mimics human MS.The goal of this preliminary study was to characterize the disease process in female Lewis rats (rEAE) using both light and transmission electron microscopy (TEM). Samples of lumbrosacral spinal cord were chosen for Initial examination. This tissue was sampled at four stages of the disease process, namely: in the primary occurrence phase (Peak 1, Day 12), the first recovery phase (Day 18), the secondary occurrence (Peak 2, Day 24) and the second recovery phase (Day 31) (see Figure 1). Lumbrosacral spinal cord tissue from non-sensitized female Lewis rats, were used as control tissue.

Download Full-text

Neural Stem Cells Derived From Primitive Mesenchymal Stem Cells Reversed Disease Symptoms and Promoted Neurogenesis in an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis

10.21203/rs.3.rs-528955/v1 ◽

2021 ◽

Author(s):

Christina Brown ◽

Christina McKee ◽

Sophia Halassy ◽

Suleiman Kojan ◽

Doug L. Feinstein ◽

...

Keyword(s):

Stem Cells ◽

Flow Cytometry ◽

Mesenchymal Stem Cells ◽

Inflammatory Response ◽

Mouse Model ◽

Experimental Autoimmune Encephalomyelitis ◽

Disease Process ◽

Blue Staining ◽

Autoimmune Encephalomyelitis ◽

Experimental Autoimmune

Abstract BackgroundMultiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). MS affects millions of people and causes a great economic and societal burden. There is no cure for MS. We used a novel approach to investigate the therapeutic potential of neural stem cells (NSCs) derived from highly proliferative human primitive mesenchymal stem cells (MSCs) in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS.MethodsMSCs were differentiated into NSCs, labeled with PKH26 and injected into the tail vein of EAE mice. The effect of transplanted cells on the disease process was assessed by neurobehavioral changes in the mice. Two weeks following cell transplantation, the animals were sacrificed to collect blood, lymphatic, and CNS tissues for analysis. Transplanted cells were tracked in various tissues by flow cytometry. Immune infiltrates were determined and characterized by H&E and immunohistochemical staining, respectively. Levels of immune regulatory cells, Treg and Th17 were analyzed by flow cytometry. Myelination was determined by Luxol fast blue staining and immunostaining. In vivo fate of transplanted cells and expression of inflammation, astrogliosis, myelination, neural, neuroprotection, and neurogenesis markers were investigated by using immunohistochemical and qRT-PCR analysis. ResultsMSC derived NSCs expressed specific neural markers, NESTIN, TUJ1, VIMENTIN and PAX6. NSCs improved EAE symptoms more than MSCs when transplanted in EAE mice. Post-transplantation analyses also showed homing of MSCs and NSCs into the CNS with concomitant induction of anti-inflammatory response resulting in reduction of immune infiltrates. NSCs also modulated Treg and Th17 cell levels in EAE mice comparable to healthy controls. Luxol fast blue staining showed significant improvement in myelination in treated mice. Further analysis showed that NSCs upregulated genes involved in myelination and neuroprotection but downregulated inflammatory and astrogliosis genes more significantly than MSCs. Importantly, NSCs differentiated into neural derivatives in the CNS and promoted neurogenesis possibly by modulating BDNF and FGF signaling pathways. ConclusionsNSC transplantation reversed the disease process by inducing an anti-inflammatory response and promoting myelination, neuroprotection, and neurogenesis in EAE disease animals. These promising results provide basis for clinical studies to treat MS using NSCs derived from primitive MSCs.

Download Full-text