Diabetes as a risk factor for Alzheimer’s disease in the Middle East and its shared pathological mediators

Jayaraj, Richard L.; Azimullah, Sheikh; Beiram, Rami

doi:10.1016/j.sjbs.2019.12.028

Cited by 69 publications

(52 citation statements)

References 216 publications

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“…Oxidative stress is regarded as a key pathological player that precedes or accompany the pathogenesis of Alzheimer's disease, type II diabetes, and skin hyperpigmentation problems [29]. Studies have shown that intake of antioxidants could prevent or delay the onset/progress of many diseases [30][31][32].…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Pharmacological and Phytochemical Profiles of Piptadeniastrum africanum (Hook.f.) Brenan Stem Bark Extracts

et al. 2020

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The stem bark (SB) of Piptadeniastrum africanum (PA) has been extensively used in African traditional medicinal systems. However, there is a dearth of scientific information regarding its possible activity in the management of type II diabetes, Alzheimer’s disease, and skin hyperpigmentation disorders. This study therefore attempted to elucidate the in vitro inhibitory action of ethyl acetate, methanol, and water extracts of P. africanum stem bark (PA-SB) on α-amylase, α-glucosidase, acetylcholinesterase, butyrylcholinesterase, and tyrosinase. Cell viability, catecholamine, and 3-hydroxykynurenine levels of hypothalamic HypoE22 cells exposed to PA-SB extracts were also investigated. The phytochemical profiles of the extracts were determined by high performance liquid chromatography (HPLC) and antioxidant properties were investigated. Saponin (867.42 mg quillaja equivalent/g) and tannin (33.81 mg catechin equivalent/g) contents were higher in the methanol extract. Multiple dihydroxy-trimethoxy(iso)flavone isomers, loliolide, eriodictyol, naringenin, luteolin, chrysoeriol, apigenin, and liquiritigenin, were characterized from PA-SB extracts using HPLC. The methanol extract of PA-SB showed highest inhibitory activity against acetylcholinesterase (4.88 mg galantamine equivalent (GALAE)/g extract), butyrylcholinesterase (5.37 mg GALAE/g extract), and tyrosinase (154.86 mg kojic acid equivalent/g extract) while α-glucosidase was effectively inhibited by the ethyl acetate extract (15.22 mmol acarbose equivalent/g extract). The methanol extract of PA-SB also showed potent antioxidant properties (493.87, 818.12, 953.07, and 732.19 mg Trolox equivalent/g extract, for 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS), cupric reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP) assays, respectively). PA-SB extracts exhibited antioxidant activity and promising inhibition against key enzymes related to type II diabetes, Alzheimer’s disease, and skin hyperpigmentation disorders. Additionally, all extracts were able to contrast hydrogen peroxide-induced oxidative stress, in HypoE22 cells, thus restoring basal catecholamine and 3-hydroxykinurenine levels, whereas only methanol and water extracts stimulated basal dopamine release. Overall, data from the present study contribute to the biological assessment of P. africanum that appears to be a promising source of natural compounds with protective and neuromodulatory effects.

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Section: Resultsmentioning

confidence: 99%

Evaluation of Pharmacological and Phytochemical Profiles of Piptadeniastrum africanum (Hook.f.) Brenan Stem Bark Extracts

et al. 2020

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“…The hallmark lesions observed in the brain of patients with AD result from the formation of numerous neurofibrillary tangles (NFTs) and senile plaques (SPs) composed of hyperphosphorylated tau and Aβ, respectively (Lane et al, 2018 ). Studies have implicated diabetes mellitus (DM) as a strong risk factor for the development of AD (Jayaraj et al, 2020 ). DM shares pathological features with AD, such as impaired insulin signaling, increased oxidative stress, increased amyloid-beta (Aβ) production, tauopathy, and cerebrovascular complications (Shinohara and Sato, 2017 ), and therefore appears to be closely related to AD.…”

Section: Introductionmentioning

confidence: 99%

Pathological Mechanisms Linking Diabetes Mellitus and Alzheimer’s Disease: the Receptor for Advanced Glycation End Products (RAGE)

Kong

Wang

et al. 2020

Front. Aging Neurosci.

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Diabetes and Alzheimer's disease (AD) place a significant burden on health care systems in the world and its aging populations. These diseases have long been regarded as separate entities; however, advanced glycation end products (AGEs) and the receptors for AGEs (RAGE) may be a link between diabetes and AD. In our study, mice injected with AGEs through stereotaxic surgery showed significant AD-like features: behavior showed decreased memory; immunofluorescence showed increased phosphorylated tau and APP. These results suggest links between diabetes and AD. Patients with diabetes are at a higher risk of developing AD, and the possible underlying molecular components of this association are now beginning to emerge.

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“…These changes refer to several structures in the temporal lobe, especially the hippocampus, considered the cerebral centre of memory and reasoning. Moreover, a previous study reported that the density of dendritic spines decreased in pyramidal cells from diabetic animals, especially in the CA1 field of hippocampus [41]. Likewise, dendritic atrophy in hippocampal neurons (CA3 field) of rats with experimentally induced diabetes was noted [42].…”

Section: Discussionmentioning

confidence: 91%

Insulin receptors in the CA1 field of hippocampus and selected blood parameters in diabetic rats fed with bilberry fruit

Matysek¹,

Borowiec²,

Szwajgier³

et al. 2021

Ann Agric Environ Med.

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Introduction. Bilberry fruit is believed to be a promising factor in the treatment of diabetes mellitus. Chronic hyperglycaemia affects the function of the central nervous system, which may be manifested as changes in hypothalamic insulin signalling. Materials and method. Using DPPH and ABTS assays, total phenolic content in bilberry fruit and its antioxidant activities were examined. The selected biochemical parameters of blood (glucose, fructosamine, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides), as well as the expression of insulin receptors, were studied in the hippocampal CA1 field of healthy and diabetic (streptozotocin-induced; 60 mg kg-1 body weight) Wistar rats fed with bilberry fruit (16 g kg-1 body weight per day; 6 weeks), as well as of the corresponding control groups. Results. Biochemical analyses revealed ambiguous results, but a significantly (P<0.05) decrease in the level of LDL-cholesterol was observed in the group of healthy rats supplemented with bilberry pulp after 6 weeks of the treatment. There was also a difference (P<0.05) in the level of LDL-cholesterol in the mentioned healthy animals fed with bilberry, versus the healthy control group. An increased number of insulin receptors-immunoreactive neurons as well as nerve fibres in the CA1 field of diabetic rats fed with bilberry fruit was also found. Conclusions. An inclusion of bilberry fruit in the daily diet during the course of diabetes can lead to plasticity of hippocampal neurons/nerve fibres, manifested by changes in insulin receptors expression. Whether or not the observed changes had protective effects (by reducing damages caused by diabetes mellitus) on the function of the central nervous system neurons needs further study.

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Diabetes as a risk factor for Alzheimer’s disease in the Middle East and its shared pathological mediators

Cited by 69 publications

References 216 publications

Evaluation of Pharmacological and Phytochemical Profiles of Piptadeniastrum africanum (Hook.f.) Brenan Stem Bark Extracts

Evaluation of Pharmacological and Phytochemical Profiles of Piptadeniastrum africanum (Hook.f.) Brenan Stem Bark Extracts

Pathological Mechanisms Linking Diabetes Mellitus and Alzheimer’s Disease: the Receptor for Advanced Glycation End Products (RAGE)

Insulin receptors in the CA1 field of hippocampus and selected blood parameters in diabetic rats fed with bilberry fruit

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