Antidiabetic Effect of Galantamine: Novel Effect for a Known Centrally Acting Drug.
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.
Department of Pharmacology & Toxicology, Faculty of Pharmacy and Drug Manufacturing, Pharos University, Alexandria, Egypt.
Mennatallah A
MA
Ali
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Hanan S
HS
El-Abhar
Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Maher A
MA
Kamel
Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Ahmed S
AS
Attia
D054392:Adipokines / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D005702:Galantamine / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects
D054392:Adipokines; D015415:Biomarkers; D001786:Blood Glucose; D002800:Cholinesterase Inhibitors; D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D007328:Insulin; D008055:Lipids; D005702:Galantamine; D045304:Cytochromes c; D053148:Caspase 3; D005947:Glucose