Combination of donepezil and gallic acid improves antioxidant status and cholinesterases activity in aluminum chloride-induced neurotoxicity in Wistar rats

Obafemi, Tajudeen Olabisi; Owolabi, Olutumise V; Omiyale, Benjamin Olusola; Afolabi, Blessing A.; Ojo, Oluwafemi Adeleke; Onasanya, A.; Adu, Isaac Adekola; Rotimi, Damilare

doi:10.1007/s11011-021-00749-w

Cited by 20 publications

(11 citation statements)

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“…Treatment with jambolan extract reversed the AlCl 3 -induced dysregulation of antioxidant systems in the brains of albino rats. These results support the theory that boosting the brain's antioxidant systems could effectively deal with neurotoxic diseases like Alzheimer's [87]. This aligns with previous research showing that conventional medicines and phenolic substances reduce oxidative stress in the brains of Alzheimer's disease rats [107,108].…”

Section: Discussionsupporting

confidence: 90%

Assessment of Anti-Alzheimer Pursuit of Jambolan Fruit Extract and/or Choline against AlCl3 Toxicity in Rats

Hawash,

Yassien,

Alotaibi

et al. 2023

Toxics

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Jambolan fruit extract and choline were investigated for Aluminum tri chloride (AlCl3)-induced Alzheimer’s disease in rats. Thirty-six male “Sprague Dawley” rats weighing (150 ± 10 g) were allocated into six groups; the first group was fed a baseline diet and served as a negative control. Alzheimer’s disease (AD) was induced in Group 2 rats by oral administration of AlCl3 (17 mg/kg body weight) dissolved in distilled water (served as a positive control). Rats in Group 3 were orally supplemented concomitantly with both 500 mg/kg BW of an ethanolic extract of jambolan fruit once daily for 28 days and AlCl3 (17 mg/kg body weight). Group 4: Rivastigmine (RIVA) aqueous infusion (0.3 mg/kg BW/day) was given orally to rats as a reference drug concomitantly with oral supplementation of AlCl3 (17 mg/kg body weight) for 28 days. Group 5 rats were orally treated with choline (1.1 g/kg) concomitantly with oral supplementation of AlCl3 (17 mg/kg body weight). Group 6 was given 500 mg/kg of jambolan fruit ethanolic extract and 1.1 g/kg of choline orally to test for additive effects concurrently with oral supplementation of AlCl3 (17 mg/kg bw) for 28 days. Body weight gain, feed intake, feed efficiency ratio, and relative brain, liver, kidney, and spleen weight were calculated after the trial. Brain tissue assessment was analyzed for antioxidant/oxidant markers, biochemical analysis in blood serum, a phenolic compound in Jambolan fruits extracted by high-performance liquid chromatography (HPLC), and histopathology of the brain. The results showed that Jambolan fruit extract and choline chloride improved brain functions, histopathology, and antioxidant enzyme activity compared with the positive group. In conclusion, administering jambolan fruit extract and choline can lower the toxic impacts of aluminum chloride on the brain.

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Section: Discussionsupporting

confidence: 90%

Assessment of Anti-Alzheimer Pursuit of Jambolan Fruit Extract and/or Choline against AlCl3 Toxicity in Rats

Hawash,

Yassien,

Alotaibi

et al. 2023

Toxics

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“…Aging with a vascular risk factor reduces cerebral blood flow, resulting in microvasculopathy with reduced NO release and localized metabolic dysfunction [60]. This study found that across all the treatment groups, only metformin and donepezil were able to significantly reduce NO levels to normal, which is consistent with results from other studies [61,62].…”

Section: Plos Onesupporting

confidence: 89%

Effects of antidiabetic agents on Alzheimer’s disease biomarkers in experimentally induced hyperglycemic rat model by streptozocin

Ali

2022

PLoS ONE

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Background Alzheimer’s disease is the most common cause of dementia in the elderly population. It is characterized by the accumulation of amyloid β and intraneuronal neurofibrillary tangles in the brain. Increasing evidence shows that the disturbance of insulin signalling in the brain may contribute to the pathophysiology of Alzheimer’s disease. In type 1 diabetes, these disruptions are caused by hypoinsulinemia, but in type 2 diabetes, they are caused by insulin resistance and decreased insulin secretion. Multiple studies have shown that diabetes is connected with an increased risk of acquiring Alzheimer’s disease. The aim of this study was to investigate the impact of anti-diabetic agents on Alzheimer’s disease progression and the levels of Alzheimer’s biomarkers in a hyperglycaemic rat model, which was induced by intraperitoneal injection of streptozocin to produce insulin-deficient diabetes. Method Thirty-six male Wistar albino rats were allocated into six groups of six rats each. Group I was the negative control group. Intraperitoneal injections of streptozocin (42mg/kg) were used once for the five experimental groups. Group II served as the positive control group. The rats in Groups III, IV, V, and VI received metformin (300mg/kg), donepezil (10mg/kg), insulin glargine (3 unit/animal), and glibenclamide (10mg/kg), respectively, for 21 days. Results Inducing hyperglycaemia in rats significantly increased the levels of serum glucose, haemoglobin A1c, total cholesterol, triglycerides, high-density lipoprotein, interleukin 6, tumour necrosis factor alpha, amyloid β 42, total plasma tau, and neurofilament light. A significant increase was also found in brain amyloid β 42, nitric oxide, acetylcholinesterase, malondialdehyde, β secretase, and phosphorylated microtubule-associated protein tau. The greatest statistically significant reductions in serum glucose, haemoglobin A1c, triglycerides, amyloid β 42, total plasma tau, brain amyloid β 42, acetylcholinesterase, and malondialdehyde were observed in rats treated with metformin. In contrast, rats treated with donepezil demonstrated the greatest statistically significant reduction in serum tumour necrosis factor alpha, brain nitric oxide, and β secretase. The levels of neurofilament light and phosphorylated microtubule-associated protein tau in the brains of rats treated with insulin glargine were significantly lower than the other treatment groups. The total cholesterol and low-density lipoprotein levels in rats treated with glibenclamide exhibited the most statistically significant reductions of all the treatment groups. Conclusions Metformin and donepezil, when administered at appropriate doses, were shown to successfully lower most plasma and brain biomarkers, including glucose, triglycerides, tumour necrosis factor alpha, amyloid β 42, nitric oxide, acetylcholinesterase, malondialdehyde, and β secretase in rats suffering from Diabetes Mellitus. As a result of this research, we suggest that metformin, either alone or in conjunction with donepezil, might be an excellent drug of choice for neuro-regeneration and risk reduction in Alzheimer’s like disease.

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“…ChEI has been shown to reduce the deposition of collagen types I and III through the inhibition of the TGF-β1/TGF-β-activated kinase1 signaling pathway via the type 2 muscarinic receptor [ 28 ]. Moreover, donepezil inhibits the TGF-β1/Smad2 signaling pathways via α7nAChR in heart transplant in rats [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Potential of Donepezil with or without Prednisolone in Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of the Anti-Inflammatory, Antioxidant, and the Antifibrotic Pathways

et al. 2023

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Background and Objectives: Bleomycin-induced pulmonary fibrosis is one of the serious complications that may limit the use of bleomycin in cancer therapy. To date, there is no effective remedy for the amelioration of this condition. Donepezil, an anti-Alzheimer’s medication, has recently been proven to exhibit potent anti-inflammatory, antioxidant, and antifibrotic effects. To the best of our knowledge, this study represents the first study designed to investigate the prophylactic effects of donepezil, either alone or in combination with the classic anti-inflammatory drug prednisolone, in bleomycin-induced pulmonary fibrosis. Methods: This study was carried out on fifty rats, which were divided into five equal groups: control (Saline) group; bleomycin group; bleomycin + prednisolone group; bleomycin + donepezil group; and bleomycin + prednisolone + donepezil group. At the end of the experiments, bronchoalveolar lavage was performed to evaluate the total and differential leucocytic counts. The right lung was processed to assess the oxidative stress markers, proinflammatory cytokines, NLRP3 inflammasome, and transforming growth factor–beta1. The left lung was subjected to histopathological and immunohistochemical examination. Results: The administration of donepezil and/or prednisolone induced a significant amelioration of oxidative stress, inflammation, and fibrosis. In addition, these animals showed a significant amelioration of the histopathological changes of fibrosis, together with a significant decline in nuclear factor kappa B (p65) immunoexpression, compared to the group treated with bleomycin alone. However, the rats treated with the donepezil/prednisolone combination showed non-significant effects on the aforementioned parameters compared to the group treated with prednisolone alone. Conclusions: Donepezil may emerge as a promising drug that shows significant prophylactic effects against bleomycin-induced pulmonary fibrosis.

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Combination of donepezil and gallic acid improves antioxidant status and cholinesterases activity in aluminum chloride-induced neurotoxicity in Wistar rats

Cited by 20 publications

References 59 publications

Assessment of Anti-Alzheimer Pursuit of Jambolan Fruit Extract and/or Choline against AlCl3 Toxicity in Rats

Assessment of Anti-Alzheimer Pursuit of Jambolan Fruit Extract and/or Choline against AlCl3 Toxicity in Rats

Effects of antidiabetic agents on Alzheimer’s disease biomarkers in experimentally induced hyperglycemic rat model by streptozocin

Ameliorative Potential of Donepezil with or without Prednisolone in Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of the Anti-Inflammatory, Antioxidant, and the Antifibrotic Pathways

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