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Neurological disturbances including cholinergic dysfunction, oxidative stress, neuroinflammation, and cognitive impairments are the well‐reported consequences of old age‐related disorders like Alzheimer's disease (AD) or dementia. Bisphosphonates were shown to ameliorate dementia in osteoporotic patients, neuroinflammation, and cholinesterase activity in rodents. Thus, the present study has been designed to examine the role of alendronate against cognitive and neurological disturbances in mice induced by a combined oral dose of d‐galactose and aluminum chloride (AlCl3) for 6 weeks. d‐galactose acts as a senescence agent, whereas AlCl3 is a neurotoxin and in combination generates neuropathologies and cognitive depletion resembling aging and AD. It was found that memory was markedly impaired in d‐galactose + AlCl3‐treated mice as assessed in different behavioral paradigms. Additionally, d‐galactose + AlCl3 led to neurotoxicity assessed on the basis of neuroinflammation, oxidative stress, glial cell activation, neuronal damage, and augmented GSK‐3β level in mice hippocampus. Consequently, alendronate administration orally for 15 days in d‐galactose + AlCl3‐exposed mice prominently reversed all these behavioral and neuropathological changes. These findings show that alendronate can be a potential therapeutic molecule with multiple targets for the management of age‐related neurological disorders such as AD. Aluminium trichloride (AlCl3) and D‐galactose act as neurotoxins and induce neuropathological changes and cognitive impairments similar to Sporadic Alzheimer's disease (SAD) and aging SAD is a most prevalent and complex neurodegenerative disease manifested by cognitive decline, senile plaques and neurofibrillary tangles. Oral dose of alendronate for 15 days attenuates AlCl3+D‐galactosed induced augmented amyloid precursor protein (APP) processing, Aβ production, GSK‐3β and associated neuroinflammation. Alendronate also found to reduce neurodegeneration and Aβ deposition in CA1 and CA3 region of mice hippocampus. [ABSTRACT FROM AUTHOR]

The current study aimed to develop alendronate (ALN)-loaded chitosan nanoparticles (CS-ALN-NPs) for brain delivery via intranasal route. These CS-ALN-NPs reduced the peripheral side effects and released ALN directly to brain. These NPs were formulated through ionic gelation technique by mixing sodium tripolyphosphate (1.5 mg/ml) in ALN-CS (1.75 mg/ml) solution. CS-ALN-NPs attained 135.75 ± 5.80 nm, 0.21 ± 0.013, 23.8 ± 3.69 mV, 72.46 ± 0.879% and 30.92 ± 0.375% mean particle size, PDI, zeta potential, entrapment efficiency and loading capacity, respectively. Furthermore, the TEM and SEM analysis of CS-ALN-NPs, respectively, revealed the particle size in 200 nm range and spherical shape. The in vitro and ex vivo release profile revealed a sustained drug release through CS-ALN-NPs as compared to pure drug solution. Also these NPs acquired a high concentration in mice brain and better pharmacokinetic profile than ALN solution (intranasal) CS-ALN-NPs were then evaluated against intracerebroventricular-streptozotocin (ICV-STZ) induced Alzheimer's disease (AD)-like pathologies in mice. The intranasal CS-ALN-NP altered the ICV-STZ induced neurobehavioral, neurochemical and histopathological changes in mice. These effects were significant to those of ALN solution (intranasal). The neuroprotective potential of CS-ALN-NPs observed in ICV-STZ mice model of AD may be a promising brain-targeted delivery system for AD treatment along with further extensive exploration at both pre-clinical and clinical edge. CS-ALN-NPs were developed and optimised to overcome the poor pharmacokinetic profile and associated side effects of ALN CS-ALN-NPs showed particle size within 200 nm range as well as controlled and sustained release in in vitro release study These optimised NPs of ALN attained higher brain:blood ratio and better pharmacokinetic profile (Cmax, tmax, AUC) CS-ALN-NPs markedly altered ICV STZ induced impairment in cognitive functions of mice and changes in APP processing, neuroinflammatory cytokines and other biochemical parameters in mice hippocampus [ABSTRACT FROM AUTHOR]

Background and Aim: A growing body of literature suggests the association between dementia risk and proton pump inhibitor (PPI) use. Therefore, we aimed to investigate the association between PPI use and dementia risk. Methods: An extensive literature search was performed in PubMed, Embase, and Cochrane till March 31, 2019. All the studies (cohort and case–control) assessing the association between PPI use and dementia risk were eligible for inclusion. Articles were selected based on the screening of title and abstract, data were extracted, and risk of bias was assessed using Newcastle–Ottawa scale. The primary outcome was pooled risk of dementia among PPI user as compared with non‐PPI user. Secondary outcomes include dementia risk based on subgroups. Statistical analysis was performed using review manager software. Results: Twelve studies (eight cohort and four case–control) were found to be eligible for inclusion. Majority of the studies were of high quality. Dementia was diagnosed based on International Classification of Diseases 9/10 codes in majority of the included studies. PPI use was not associated with the dementia risk, with a pooled relative risk (RR) of 1.05 (95% confidence interval [CI]: 0.96–1.15), P = 0.31. Subgroup analysis based on study design (cohort: P = 0.14; case–control: P = 0.14), sex (RR 1.25 [95% CI: 0.97–1.60], P = 0.08), histamine 2 receptor antagonist blockers (P = 0.93), and Alzheimer's disease (RR 1.00 [95% CI: 0.91–1.09], P = 0.93) revealed no significant association between PPI use and dementia risk. Conclusion: We found no significant association between PPI use and the risk of dementia or Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Objectives: The growing rate of neurological disorders is a major concern in today's scenario. Today's research is focusing on therapeutic interventions providing benefits in these disorders. Presently, drugs of natural origin have gained more interest for the treatment of central nervous system disorders for their efficacy and less/no side effects. This review is emphasizing the cited roles of Trigonella foenum graecum (fenugreek) and its constituents in different neurological manifestations. Method: A review of the literature, relevant to the role of fenugreek and its major constituents including saponins and alkaloids in different neurological aspects and in delineating the health benefits, was conducted. Results: The cited research acknowledged that fenugreek and its constituents exert positive influence on neurological health. Few studies have reported the beneficial role of fenugreek and its constituents like trigonelline in pathological symptoms of Alzheimer's disease. Similarly, other studies evidenced the neuroprotective, antidepressant, antianxiety as well as modulatory effect on cognitive functions and Parkinson's disease. Discussion: Large populations are the sufferers of the neurological disorders, pointing the need for investigation of such therapeutic interventions which target and delay the underlying pathological hallmarks and exert positive influence on different neurological health problems. Hypolipidemic, hypoglycemic, antioxidant, and immunomodulatory effects of fenugreek and its constituents with their potential role in various neurological disorders were already reported. In future, it would be of even greater interest to further develop more effective dosage, supplementation period, and to evaluate the therapeutic potentials of fenugreek and its constituents in neurological disorders by exploring underlying cellular and molecular mechanisms. [ABSTRACT FROM AUTHOR]

Apigenin is a natural polyphenolic compound widely distributed as a glycoside in fruits and vegetables. Apigenin belongs to BCS class II with low solubility, which leads to poor absorption and bioavailability. It is mostly absorbed from the small intestine and extensively metabolized through glucuronidation and sulfation processes. Apigenin is known for its antioxidant and anti-inflammatory properties. It is also used as a chemopreventive drug in the management of various cancers. Pharmacological effects of apigenin have a wide range, from neuroprotective to treating renal disorders. Apigenin is non-toxic in nature and acts through various pathways (JAK/STAT, Wnt/β-catenin, MAPK/ERK, PI3K/Akt, and NF-κB) to exert its therapeutic efficacy. Numerous formulations have been researched to enhance the bioavailability and pharmacological effects of apigenin. Combinatorial therapies are also researched to minimize the side-effects of chemotherapeutic drugs. The review presents pharmacokinetic and pharmacodynamic aspects of apigenin. Apigenin is safe for the treatment and management of numerous diseases. It can be easily incorporated into nanoformulation alone or in combination with other active ingredients to widen the therapeutic window. This review intends to help in drug optimization and therapeutic efficacy maximization for future studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's disease (AD) is the most devastating neurodegenerative disorder, accounting over 46 million cases of dementia globally. Evidence supports that Brain Insulin Resistance (BIR) due to serine phosphorylation of Insulin Receptor Substrate-1 (IRS-1) has an association with AD. GLP-1 an incretin hormone, rapidly degraded by Dipeptidyl Peptidase-4 (DPP-4) has also confirmed its efficacious role in AD. Linagliptin, a DPP-4 inhibitor is hypothesized to increase GLP-1 level, which then crosses Blood Brain Barrier (BBB), decreases Amyloid-beta (Aβ) and insulin resistance in hippocampus. Thus, the present study was designed to evaluate Linagliptin in Aβ (1-42) peptides induced rat model of AD. Following 1 week of induction, rats were administered with Linagliptin (0.513 mg/kg, 3 mg/kg, and 5 mg/kg) orally for 8 weeks and donepezil (5 mg/kg) as a reference standard. At the end of scheduled treatment neurobehavioral parameters were assessed. After this, rats were sacrificed, hippocampus was isolated from the whole brain for histopathological analysis and biochemical parameters estimation. Linagliptin dose-dependently and significantly reversed motor and cognitive impairment, assessed through locomotor activity (LA) and Morris water maze (MWM) test respectively. Moreover, Linagliptin augmented GLP-1 level and attenuated soluble Aβ (1-42), IRS-1 (s307), GSK-3β, TNF-α, IL-1β, IL-6, AchE and oxidative/nitrosative stress level in hippocampus. H&E and Congo red staining also exhibited neuroprotective and anti-amylodogenic effect respectively. Our study findings implies the significant effect of Linagliptin in reversing the behavioural and biochemical deficits by altering Aβ (1-42) and BIR via IRS-1 confirming one of the mechanism underlying the pathophysiology of AD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Currently, a large number of people throughout the world are affected by neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease which appear with a lapse in recall, attention and altered cognitive functions. Learning and memory, the fundamental indices defining cognitive functions, are the complex psychological processes governing acquisition, consolidation, and retrieval of stored information. These processes are synchronized by the coordination of various parts of the brain including hippocampus, striatum and amygdala., Objective: The present review is centered on different behavioral paradigms in rodents interpreting learning and memory both explicitly and implicitly. Furthermore, it is also emphasizing on the interaction of various brain structures during different stages of associative, spatial and non-spatial memory., Methods: We embarked on an objective review of literature relevant to screening methods for evaluation of drug's influence on a wide range of cognitive functions (learning and memory) as well as the underlying mechanism responsible for modulation of these functions., Results: Our review highlighted the behavioral paradigms based on associative, spatial/nonspatial and working memory. The cited research acknowledged the hippocampal and striatal control on learning and memory., Conclusion: Since the neurodegenerative disorders and dementia have continuously been increasing, a wide range of therapeutic targets have been developed at the cellular and molecular level. This arises the necessity of screening of these targets in different cognitive behavioral paradigms which reflect their memory enhancing potential. The understanding of behavioral models and the involvement of brain structures in cognitive functions highlighted in the present review might be helpful to advance therapeutic interventions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)