Antidiabetic Effect of Galantamine: Novel Effect for a Known Centrally Acting Drug

Abstract

The cholinergic anti-inflammatory pathway is one of the putative biochemical pathways that link diabetes with Alzheimer disease. Hence, we aimed to verify the potential antidiabetic effect of galantamine, unveil the possible mechanisms and evaluate its interaction with vildagliptin. The n5-STZ rat model was adopted and the diabetic animals were treated with galantamine and/or vildagliptin for 4 weeks. Galantamine lowered the n5-STZ-induced elevation in body weight, food/water intake, serum levels of glucose, fructosamine, and ALT/AST, as well as AChE in the tested organs. Moreover, it modulated successfully the lipid profile assessed in serum, liver, and muscle, and increased serum insulin level, as well as % β-cell function, in a pattern similar to that of vildagliptin. Additionally, galantamine confirmed its antioxidant (Nrf2, TAC, MDA), anti-inflammatory (NF-κB, TNF-α, visfatin, adiponectin) and anti-apoptotic (caspase-3, cytochrome c) capabilities by altering the n5-STZ effect on all the aforementioned parameters. On the molecular level, galantamine/vildagliptin have improved the insulin (p-insulin receptor, p-Akt, GLUT4/GLUT2) and Wnt/β-catenin (p-GSK-3β, β-catenin) signaling pathways. On almost all parameters, the galantamine effects surpassed that of vildagliptin, while the combination regimen showed the best effects. The present results clearly proved that galantamine modulated glucose/lipid profile possibly through its anti-oxidant, -apoptotic, -inflammatory and -cholinesterase properties. These effects could be attributed partly to the enhancement of insulin and Wnt/β-catenin signaling pathways. Galantamine can be strongly considered as a potential antidiabetic agent and as an add-on therapy with other oral antidiabetics.

Neural circuitry and immunity

“…In addition, galantamine lowers leptin, resistin and IL-6 levels and attenuates fatty liver disease in these mice [164]. A very recent study significantly substantiated these findings by demonstrating the therapeutic anti-inflammatory and disease-alleviating efficacy of galantamine in an animal model of type 2 diabetes [167]. These beneficial metabolic and anti-inflammatory effects of galantamine, other cholinergic modalities and VNS in experimental settings of obesity and type 2 diabetes provide a platform for further exploration of these approaches in the treatment of obesity-related disorders [6].…”

Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in the Quest for the Molecules With Therapeutic and Preventive Potential

“…Conversely, the natural compound galantamine ( 10 )—another FDA‐approved drug for AD (Table )—has just been pointed out as a potential antidiabetic agent. Indeed, besides the well‐known cholinesterase inhibitory activity, galantamine was found to decrease plasma glucose and insulin levels, while improving insulin signaling pathways, lipid metabolism, and β‐cell function . These data, on top of its antioxidant, anti‐inflammatory and antiapoptotic activity, makes galantamine an excellent example of how nature can be explored toward the discovery of multitarget drug‐like molecules.…”

Arabic gum acacia improves diabetic peripheral neuropathy in rats: a biochemical and histopathological evidence

“…Induction of DM was done using intra-peritoneal injection of STZ once at the dose of 60mg/Kg. 10 Metformin was administered at the dose 300mg/kg according to Mennatallah et al 11 Vitamin B12 was administered at the dose 1.77mg/kg according to Hosseinzadeh. 12 Arabic Gum was administered at the dose of 4gm/kg.…”