GLP-1 nanomedicine alleviates gut inflammation

Anbazhagan, Arivarasu Natarajan; Thaqi, Mentor; Priyamvada, Shubha; Jayawardena, Dulari; Kumar, Anoop; Gujral, Tarunmeet; Chatterjee, Ishita; Mugarza, Edurne; Saksena, Seema; Önyüksel, Hayat; Dudeja, Pradeep K.

doi:10.1016/j.nano.2016.08.004

Cited by 52 publications

(40 citation statements)

References 30 publications

(43 reference statements)

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“…As has been previously established, CCL20 is a key chemokine for CCR6 + Th17 cells ( 83 ), while IL-33 and IL-22 are the representative cytokines for Th2 and Th17 immune responses, respectively ( 84 , 85 ). In line with above results, GLP-1 in sterically stabilized phospholipid micelles (GLP-1-SSM), showing a long half-life and resistant to DPP-4, markedly alleviated the development of DSS-induced mice colitis by reducing the expression of pro-inflammatory cytokine IL-1β ( 86 ). Moreover, intestinal epithelial architecture in a colitis model with GLP-1-SSM administration was significantly improved.…”

Section: Effects Of Glp-1 On Ibdsupporting

confidence: 65%

Role of Incretin Axis in Inflammatory Bowel Disease

et al. 2017

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The inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory conditions of the gastrointestinal tract and involve a complicated reciprocity of environmental, genetic, and immunologic factors. Despite substantial advances in the foundational understanding of the immunological pathogenesis of IBD, the detailed mechanism of the pathological progression in IBD remains unknown. In addition to Th1/Th2 cells, whose role in IBD has been previously well defined, recent evidence indicates that Th17 cells and Tregs also play a crucial role in the development of IBD. Diets which contain excess sugars, salt, and fat may also be important actors in the pathogenesis of IBD, which may be the cause of high IBD incidence in western developed and industrialized countries. Up until now, the reason for the variance in prevalence of IBD between developed and developing countries has been unknown. This is partly due to the increasing popularity of western diets in developing countries, which makes the data harder to interpret. The enterocrinins glucagon-like peptides (GLPs), including GLP-1 and GLP-2, exhibit notable benefits on lipid metabolism, atherosclerosis formation, plasma glucose levels, and maintenance of gastric mucosa integrity. In addition to the regulation of nutrient metabolism, the emerging role of GLPs and their degrading enzyme dipeptidyl peptidase-4 (DPP-4) in gastrointestinal diseases has gained increasing attention. Therefore, here we review the function of the DPP-4/GLP axis in IBD.

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Section: Effects Of Glp-1 On Ibdsupporting

confidence: 65%

Role of Incretin Axis in Inflammatory Bowel Disease

et al. 2017

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“…41,42 Previously, we have demonstrated the preventive capacity of another neuropeptide (glucagon like peptide-1) in SSM, in ameliorating DSS induced colitis. 43 In line with that, in this study, we moved to investigate the benefit of the potent immunomodulatory peptide hormone VIP in DSS colitis. Loss of VIP levels in the intestine has been implicated to play an important role during the pathogenesis of human IBD and in rodent models of colitis.…”

Section: Discussionmentioning

confidence: 85%

Vasoactive Intestinal Peptide Nanomedicine for the Management of Inflammatory Bowel Disease

Jayawardena¹,

Anbazhagan²,

Guzman³

et al. 2017

Mol. Pharmaceutics

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Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine, with increasing incidence worldwide. At present, the management of IBD is an unmet medical need due to the ineffectiveness of currently available drugs in treating all patients, and there is strong demand for novel therapeutics. In this regard, vasoactive intestinal peptide, a potent anti-inflammatory endogenous hormone, has shown promise in managing multiple immune disorders in animal models. However, when administered in the free form, VIP undergoes rapid degradation in vivo, and with continuous infusion, it causes severe dose limiting side effects. To overcome these barriers, we have developed a superior mode to deliver VIP in its native form, using sterically stabilized micelles (VIP-SSM). Our previous studies demonstrated that, VIP, when administered in SSM, prevented joint damage and inflammation in a mouse model of rheumatoid arthritis at a significantly lower dose than the free peptide, completely abrogating the serious side effect of hypotension associated with VIP. In the current study, we demonstrate the therapeutic benefit of VIP-SSM over free peptide in reversing severe colitis associated with IBD. First, we conducted preliminary studies with dextran sulfate sodium (DSS) induced colitis in mice, to determine the effectiveness of VIP administered on alternate days in reducing disease severity. Thereafter, a single intra peritoneal injection of VIP-SSM or the free peptide was used to determine its therapeutic effect on the reversal of colitis and associated diarrhea. The results demonstrated that when administered on alternate days, both VIP-SSM and VIP were capable of alleviating DSS colitis in mice. However, when administered as a single dose, in a therapeutic setting, VIP-SSM showed superior benefits compared to the free peptide in ameliorating colitis phenotype. Namely, the loss of solid fecal pellets and increased fluid accumulation in colon resulting from DSS insult was abrogated in VIP-SSM treated mice and not with free VIP. Furthermore, reduced protein and mRNA levels of the major chloride bicarbonate exchanger, down regulated in adenoma (DRA), seen with DSS was reversed with VIP-SSM, but not with the free peptide. Similarly, VIP-SSM treatment significantly reduced the elevated mRNA levels of pro-inflammatory cytokines and showed significant histologic recovery when compared to mice treated with free VIP. Therefore, these results demonstrated that as a single dose, the anti-inflammatory and antidiarrheal effects of VIP can be achieved effectively when administered as a nanomedicine. Therefore, we propose VIP-SSM to be developed as a potential therapeutic tool for treating ulcerative colitis, a type of IBD.

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“…Indeed, therapeutic use of peptides or agonists has been beneficial in mouse models, GLP-2 can rescue DSS colitis 163 and small intestinal enteritis 164,165 possibly by reducing bacterial translocation, 166 while nanodelivery of GLP-1 is also protective. 167 Taken together this suggests that eecs play an essential and varied role in the pathology of IBD and are strong candidates for therapeutic intervention. 168 As is often the case, the majority of initial observations have arisen from readily available chemical models of IBD, and while these results remain valid, new scientific knowledge is likely to arise by examining the influence of eecs in more complex models which better relate to IBD.…”

Section: Inflammatory Bowel Disease-animal Modelsmentioning

confidence: 99%

Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity

2018

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The intestinal epithelium must balance efficient absorption of nutrients with partitioning commensals and pathogens from the bodies' largest immune system. If this crucial barrier fails, inappropriate immune responses can result in inflammatory bowel disease or chronic infection. Enteroendocrine cells represent 1% of this epithelium and have classically been studied for their detection of nutrients and release of peptide hormones to mediate digestion. Intriguingly, enteroendocrine cells are the key sensors of microbial metabolites, can release cytokines in response to pathogen associated molecules and peptide hormone receptors are expressed on numerous intestinal immune cells; thus enteroendocrine cells are uniquely equipped to be crucial and novel orchestrators of intestinal inflammation. In this review, we introduce enteroendocrine chemosensory roles, summarize studies correlating enteroendocrine perturbations with intestinal inflammation and describe the mechanistic interactions by which enteroendocrine and mucosal immune cells interact during disease; highlighting this immunoendocrine axis as a key aspect of innate immunity.

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GLP-1 nanomedicine alleviates gut inflammation

Cited by 52 publications

References 30 publications

Role of Incretin Axis in Inflammatory Bowel Disease

Role of Incretin Axis in Inflammatory Bowel Disease

Vasoactive Intestinal Peptide Nanomedicine for the Management of Inflammatory Bowel Disease

Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity

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