ArticleJournal of diabetes and metabolic disorders2020
Metformin/Donepezil combination modulates brain antioxidant status and hippocampal endoplasmic reticulum stress in type 2 diabetic rats.
Article in Journal of diabetes and metabolic disorders, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Effects of metformin and exercise on Alzheimer's model induced by D-galactose in the rats: A behavioral, histological and BDNF gene study.Biochemistry and biophysics reports · 2026Article
- Obesity as a catalyst for neurodegeneration.Nature metabolism · 2026Review
- Neuroprotective mechanisms of nutraceutical berberine: Preclinical evidence and future perspectives.Advances in neurotoxicology · 2026Article
- Metformin attenuates endoplasmic reticulum stress in diabetic kidney disease: mechanistic insights and future perspectives.International urology and nephrology · 2025Review
- Novel targets and therapies of metformin in dementia: old drug, new insights.Frontiers in pharmacology · 2024Review
- Assessment of Anti-Alzheimer Pursuit of Jambolan Fruit Extract and/or Choline against AlClToxics · 2023Article
- Article
- Combined Donepezil with Astaxanthin via Nanostructured Lipid Carriers Effective Delivery to Brain for Alzheimer's Disease in Rat Model.International journal of nanomedicine · 2023Article
- Effects of antidiabetic agents on Alzheimer's disease biomarkers in experimentally induced hyperglycemic rat model by streptozocin.PloS one · 2022Article
- Review
- Combination of donepezil and gallic acid improves antioxidant status and cholinesterases activity in aluminum chloride-induced neurotoxicity in Wistar rats.Metabolic brain disease · 2021Article
- Metformin a Potential Pharmacological Strategy in Late Onset Alzheimer's Disease Treatment.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases.Nature reviews. Cardiology · 2021Review
- Article
- Combined effect of metformin and gallic acid on inflammation, antioxidant status, endoplasmic reticulum (ER) stress and glucose metabolism in fructose-fed streptozotocin-induced diabetic rats.Toxicology reports · 2021Article
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Authors and funding
7 authors.
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Abstract
purposeDiabetes mellitus is associated with perturbations in brain biochemical parameters associated with dementia. This study aimed at comparing the effect of metformin and metformin/donepezil combination on oxidative stress, endoplasmic reticulum stress and inflammation in the brain of diabetic Wistar rats.
methodsDiabetes was induced by single intraperitoneal injection of 40 mg/kg streptozotocin after administration of 10% fructose for 14 days. Animals were randomly assigned to four groups of five animals each. Group 1 was the normal control and received only distilled water. Groups 2 and 3 were diabetic rats treated with metformin/donepezil combination and metformin only respectively, while group 4 was diabetic control. Treatment lasted for 21 days after confirmation of diabetes. Activities of acetylcholinesterase (AchE), butyrylcholinesterase (BchE), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase were evaluated in the brain of diabetic rats. Enzyme-linked immunosorbent assay was used to estimate brain levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) malondialdehyde and glucose transporter-4 (GLUT4), while expression of endoplasmic reticulum stress markers - glucose regulated protein-78 (GRP78), activating transcription factor-4 (ATF4) and C/EBP homologous protein (CHOP) was determined using real-time PCR in the hippocampus of diabetic rats.
resultsTreatment with metformin/donepezil combination significantly reduced the activities of AchE, BchE as well as levels of malondialdehyde, TNF-α and IL-6, while the activities of SOD, GPx and catalase were significantly increased in the brain. Moreover, expression of ER stress markers was attenuated in the hippocampus.
conclusionMetformin/donepezil combination appeared more efficacious than metformin only and could be considered for managing diabetes-associated dementia.
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