Exploring the multifaceted neuroprotective actions of gallic acid: a review

Much attention has been recently given to the effect of diet compounds on physical and mental health. Gallic acid is a phenolic compound with antioxidant activity. This compound is widely presented in black tea leaves, green tea, apples, grapes, strawberries, and pineapples. During the past years, it has been reported that gallic acid is effective against nervous system's disorders including Alzheimer's disease, Parkinson's disease, ischemia, and reperfusion, depression and anxiety. These indicate that gallic acid can be considered as a valuable agent for nutraceutical interventions. In this study, several clinical studies suggested that gallic acid can improve human health by preventing or delaying the onset of neurological diseases. The present study indicated the neuroprotective features of gallic acid including the pre-clinical evidence for its effects in AD and PD and other diseases related to the nervous system. Significant efforts are required to confirm the neuroprotective effects of gallic acid in treating the diseases related to the nervous system. Keywords:Gallic acid; neurodegenerative diseases; Parkinson; psychiatric disorder

A mechanistic view on the neurotoxic effects of air pollution on central nervous system: risk for autism and neurodegenerative diseases

Many reports have shown a strong association between exposure to neurotoxic air pollutants like heavy metal and particulate matter (PM) as an active participant and neurological disorders. While the effects of these toxic pollutants on cardiopulmonary morbidity have principally been studied, growing evidence has shown that exposure to polluted air is associated with memory impairment, communication deficits, and anxiety/depression among all ages. So, these toxic pollutants in the environment increase the risk of neurodegenerative disease, ischemia, and autism spectrum disorders (ASD). The precise mechanisms in which air pollutants lead to communicative inability, social inability, and declined cognition have remained unknown. Various animal model studies show that amyloid precursor protein (APP), processing, oxidant/antioxidant balance, and inflammation pathways change following the exposure to constituents of polluted air. In the present review study, we collect the probable molecular mechanisms of deleterious CNS effects in response to various air pollutants. Graphical abstract: Figure not available: see fulltext

Therapeutic effects of levothyroxine in a rat model of scopolamine-induced cognitive impairment: An electrophysiological, behavioral, and biochemical study

Scopolamine (SCOP), an anticholinergic drug, is commonly used for inducing a cognitive deficiency in experimental animal models. Ninety six Wistar male rats were divided into six groups [Control, Control + Levothyroxine (L-T4, 100), SCOP + Vehicle, SCOP + L-T4 (50 and 100), SCOP + donepezil (DP)]. During 21 consecutive days, SCOP (1 mg/kg, i.p.) was used with the purpose of inducing an animal model of cognitive impairment. Thirty min after the administration of SCOP, animals were treated with 50 and 100 mg/kg L-T4, 3 mg/kg of DP, or normal saline for 21 days. The behavioral (passive avoidance and spatial memory, anxiety, depression, locomotion, and motor coordination), and electrophysiological (hippocampal long-term potentiation (LTP)) assessments, as well as biochemical changes, were estimated. Results indicated that the indices of depression/anxiety, spatial/passive avoidance memory, motor coordination, LTP records (amplitude and slope), and antioxidant enzyme activity were significantly decreased in SCOP groups in comparison with the control. Compared to the control group, L-T4 (50 and 100 mg/kg) treated rats showed significant improvements in memory and learning deficits, anxiety, all LTP parameters, and the antioxidant enzyme concentrations. The cerebral contents of tumor necrosis factor-alpha (TNF-α) in the L-T4 and DP treated groups were significantly lower than that of the SCOP + Veh group (p < 0.01). This research showed that the L-T4 prevented the disruption of synaptic plasticity and cognitive deficiencies induced by SCOP. The beneficial effects of L-T4 may be due to a decrease in the concentration of TNF-α and enhancement of the antioxidant content in the hippocampus

The ameliorative effects of myricetin on neurobehavioral activity, electrophysiology, and biochemical changes in an animal model of traumatic brain injury

Traumatic brain injury (TBI) can produce cognitive disabilities and death. The most frequent clinical symptoms of TBI are memory loss and unusual behavior or mental health disorders. The present study was aimed to evaluate the effects of chronic oral administration of myricetin (MYR) on behavioral activities (spatial and passive avoidance memory, and motor coordination) and long-term potentiation (LTP) from cornu ammonis area as well as malondialdehyde (MDA) levels in the rat hippocampus following TBI. Brain injury was induced following Marmarou's method. Motor balance, spatial memory test, and passive avoidance task (PAT) were assessed in the Rotarod, Morris water maze, and shuttle-box apparatus, respectively. The level of MDA was measured by ELISA kits and LTP indices were recorded by Electromadule. The results indicated that step-through latency (p < 0.001), LTP indices (p < 0.001) at different times, the percentage of the total time spent by animals in the target quarter (p < 0.001), and the latency times (p < 0.001) were reduced significantly in the TBI rats compared with those of the control group but enhanced significantly in the group treated with MYR compared with those of the TBI group. Motor coordination decreased in the group with TBI (p < 0.001 vs. control). Also, the cerebral MDA concentrations increased following TBI (p < 0.001) and significantly decreased in the group treated with MYR (p < 0.01). MYR improved neurological scores (p < 0.001), memory (p < 0.05, p < 0.01, p < 0.001 at different time points) and LTP indices (p < 0.001) compared with those of the TBI group significantly. The results suggested that MYR could be used as a neuroprotective agent against TBI-induced electrophysiological and behavioral deficits. Several lines of studies are needed to elucidate the possible molecular mechanism of MYR involved in improving cognitive impairments. keywords: CognitionLong-term potentiationMyricetinRatsTraumatic brain injur

The regulation of pituitary-thyroid abnormalities by Peripheral administration of Levothyroxine increased BDNF and Reelin proteins expression in an animal model of Alzheimer’s disease

Alzheimer's disease (AD) is associated with decreased serum levels of thyroid hormones (THs), increased levels of thyroid-stimulating hormone (TSH) and decreased in protein expression of brain-derived neurotrophic factor (BDNF) and reelin in the hippocampus. In this study, we have evaluated the effect of subcutaneously (SC) administration of levothyroxine (L-T4) on levels of THs and TSH as well as protein expression of BDNF and reelin in AD rats. To make an animal model of AD, Beta-amyloid (Aβ) plus ibotenic acid were infused intrahippocampally (IH), and rats were treated with L-T4 and/or saline for 10 days. The levels of THs and TSH were measured by ELISA kits. Protein synthesis was detected by Western Blotting method. Results have been shown that serum level of THs, BDNF and reelin protein expression in the hippocampus were significantly decreased (pThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

The effect of triiodothyronine on the hippocampal long-term potentiation in an animal model of the Alzheimer's disease: The role of BDNF and reelin

Converging evidence, propose a close relation between thyroid function and Alzheimer's disease (AD). We have assessed the effect of subcutaneous and intrahippocampal administrations of triiodothyronine (T3) on the electrophysiological activity (hippocampal long-term potentiation (LTP)), the levels of thyroid hormones (THs) and TSH, the protein expression of BDNF and reelin as well as histological changes in the hippocampus of AD rats. Beta-amyloid (Aβ) plus ibotenic acid (Ibo) were injected intrahippocampally and rats were treated with T3 or saline. The hippocampal levels of THs and the protein expression are measured by ELISA kits and Western blotting method respectively. Results have been shown that T3 (S.C., and I. H), significantly reversed the amplitude and the slope impairment of the DG neurons, induced by Aβ. The hippocampal levels of THs, TSH and two protein expression were significantly decreased (p < 0.001) in AD animals and increased significantly in AD rats that have received T3 (S. C and I. H) (p < 0.01). Formation of amyloid plaques was declined in AD rats treated with T3. In conclusion, both S.C., and I.H. injections of T3 is effective in preventing the disruption of synaptic plasticity induced by Aβ. This positive effect of T3 may be mediated through a regulation of proteins expression and the hippocampal level of THs. The best effect was observed in I.H. microinjection of T3. keywords Alzheimer's disease Brain-derived neurotrophic factor Ibotenic acid Reelin Triiodothyroni

Protective effects of vanillic acid on autistic-like behaviors in a rat model of maternal separation stress: Behavioral, electrophysiological, molecular and histopathological alterations

Compounds derived from herbs exhibit a range of biological properties, including anti-inflammatory, antioxidant, and neuroprotective properties. However, the exact mechanism of action of these compounds in various neurological disorders is not fully discovered yet. Herein, the present work detected the effect of Vanillic acid (VA), a widely-used flavoring agent derived from vanillin, on autistic-like behaviors to assess the probable underlying mechanisms that mediate behavioral, electrophysiological, molecular, and histopathological alterations in the rat model of maternal separation (MS) stress. Maternal separated rats were treated with VA (25, 50, and 100 mg/kg interperitoneally for 14 days). In addition, anxiety-like, autistic-like behaviors, and learning and memory impairment were evaluated using various behavioral tests. Hippocampus samples were assessed histopathologically by H&E staining. Levels of malondialdehyde (MDA) and antioxidant capacity (by the FRAP method), as well as nitrite levels, were measured in brain tissue. Moreover, gene expression of inflammatory markers (IL-1β, TLR-4, TNF-α, and NLRP3) was evaluated in the hippocampus. Electrophysiological alterations were also estimated in the hippocampus by long-term potentiation (LTP) assessments. Results showed that VA reversed the negative effects of MS on behavior. VA increased the diameter and decreased the percentage of dark neurons in the CA3 area. Accordingly, VA decreased MDA and nitrite levels and increased the antioxidant capacity in brain samples and decreased the expression of all inflammatory genes. VA treated rats showed significant improvements in all LTP parameters. This study provided evidence suggesting a possible role for VA in preventing autism spectrum disorder (ASD) by regulating immune signaling

Neuroprotective properties of Betulin, Betulinic acid, and Ursolic acid as triterpenoids derivatives: a comprehensive review of mechanistic studies

Cognitive deficits are the main outcome of neurological disorders whose occurrence has risen over the past three decades. Although there are some pharmacologic approaches approved for managing neurological disorders, it remains largely ineffective. Hence, exploring novel nature-based nutraceuticals is a pressing need to alleviate the results of neurodegenerative diseases, such as Alzheimer’s disease (AD) and other neurodegenerative disorders. Some triterpenoids and their derivates can be considered potential therapeutics against neurological disorders due to their neuroprotective and cognitive-improving effects. Betulin (B), betulinic acid (BA), and ursolic acid (UA) are pentacyclic triterpenoid compounds with a variety of biological activities, including antioxidative, neuroprotective and anti-inflammatory properties. This review focuses on the therapeutic efficacy and probable molecular mechanisms of triterpenoids in damage prevention to neurons and restoring cognition in neurodegenerative diseases. Considering few studies on this concept, the precise mechanisms that mediate the effect of these compounds in neurodegenerative disorders have remained unknown. The findings can provide sufficient information about the advantages of these compounds against neurodegenerative disease