Brain Malondialdehyde Levels Research Articles

Ex Vivo Antioxidant and Cholinesterase Inhibiting Effects of a Novel Galantamine–Curcumin Hybrid on Scopolamine-Induced Neurotoxicity in Mice

Oxidative stress is an essential factor in the development and progression of Alzheimer's disease (AD). An excessive amount of reactive oxygen species (ROS) induces the peroxidation of lipid membranes, reduces the activity of antioxidant enzymes and causes neurotoxicity. In this study, we investigated the antioxidant and cholinesterase inhibitory potential of a novel galantamine-curcumin hybrid, named 4b, administered orally in two doses (2.5 mg/kg and 5 mg/kg) in scopolamine (SC)-induced neurotoxicity in mice. To evaluate the effects of 4b, we used galantamine (GAL) (3 mg/kg) and curcumin (CCN) (25 mg/kg) as positive controls. Ex vivo experiments on mouse brains showed that the higher dose of 4b (5 mg/kg) increased reduced glutathione (GSH) levels by 46%, catalase (CAT) and superoxide dismutase (SOD) activity by 57%, and glutathione peroxidase (GPx) activity by 108%, compared with the SC-treated group. At the same time, 4b (5 mg/kg) significantly reduced the brain malondialdehyde (MDA) level by 31% and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities by 40% and 30%, respectively, relative to the SC-impaired group. The results showed that 4b acted as an antioxidant agent and brain protector, making it promising for further experimental research in the field of neurodegenerative diseases.

Dichrocephala integrifolia Aqueous Extract Antagonises Chronic and Binges Ethanol Feeding-Induced Memory Dysfunctions: Insights into Antioxidant and Anti-Inflammatory Mechanisms.

Ethanol consumption is widely accepted despite its addictive properties and its mind-altering effects. This study aimed to assess the effects of Dichrocephala integrifolia against, memory impairment, on a mouse model of chronic and binges ethanol feeding. Mice were divided, into groups of 8 animals each, and received distilled water, Dichrocephala integrifolia aqueous extract (25; 50; 100; or 200 mg/kg) or memantine (200 mg/kg) once a day, while fe, with Lieber-DeCarli control (sham group only) or Lieber-DeCarli ethanol diet ad libitum for 28 days. The Y maze and the novel object recognition (NOR) tests were used to evaluate spatial short-term and recognition memory, respectively. Malondialdehyde, nitric oxide, glutathione levels, and proinflammatory cytokines (Il-1β, TNF-α, and Il-6) were evaluated in brain homogenates following behavioral assessments. The results showed that chronic ethanol administration in mice was associated with a significant (p < 0.001) reduction in the spontaneous alternation percentage and the discrimination index, in the Y maze and the NOR tests, respectively. It significantly (p < 0.01) increased oxidative stress and inflammation markers levels in the brain. Dichrocephala integrifolia (100 and 200 mg/kg) as well as memantine (200 mg/kg) significantly (p < 0.001) increased the percentage of spontaneous alternation and the discrimination index, in the Y maze and NOR tests, respectively. Dichrocephala integrifolia (100 and 200 mg/kg) likewise memantine (200 mg/kg) significantly (p < 0.01) alleviated ethanol-induced increase, in the brain malondialdehyde level, nitric oxide, Il-1β, TNF-α, and Il-6. From these findings, it can be concluded that Dichrocephala integrifolia counteracted memory impairment, oxidative stress, and neuroinflammation induced by chronic ethanol consumption in mice.

Antidepressant Effect of Crocin in Mice with Chronic Mild Stress.

This study aimed to investigate the antidepressant property of crocin (Crocetin digentiobiose ester) using a chronic mild stress (CMS)-induced depression model in experimental mice. The tail suspension test (TST) and the sucrose preference test were used to evaluate the antidepressant effect on albino mice of either sex after three weeks of CMS. The period of immobility in the TST and percentage preference for sucrose solution were recorded. By monitoring brain malondialdehyde (MDA) level, catalase (CAT) activity, and reduced glutathione (GSH) level, the antioxidant potential was assessed. Three dosages of crocin (4.84, 9.69, and 19.38 mg/kg) were evaluated. When compared to controls, animals that received crocin administration during three periods of CMS had considerably shorter immobility times during the TST. Crocin treatment also raised the percentage preference for sucrose solution in a dose-dependent manner, bringing it to parity with the conventional antidepressant, imipramine. Animals that received a high dose of crocin had a much greater spontaneous locomotor activity. Furthermore, a high dose of crocin remarkably lowered plasma corticosterone and nitrite levels brought on by CMS. Additionally, high doses of crocin given during CMS greatly enhanced reduced glutathione levels while considerably reducing the brain’s MDA and catalase activities. In conclusion, high doses of crocin may have an antidepressant effect in an animal model through several mechanisms. However, further studies should be carried out to explore the role of neurotransmitters for their antidepressant property.

Influence of methadone on the anticonvulsant efficacy of valproate sodium gabapentin against maximal electroshock seizure in mice by regulation of brain MDA TNF-α.

Methadone is the most frequently used opioid therapy worldwide, with controversial effects on oxidative stress homeostasis. This study investigated the effects of intraperitoneal (i.p.) co-administration of methadone (0.1, 0.3, 1, and 3 mg/kg) and valproate sodium (300 mg/kg) or gabapentin (50 mg/kg) in the mice maximal electroshock (MES)-induced seizure model. The adverse effect of drugs was assessed using the chimney test. The levels of tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) contents were measured in mice brains after a single seizure. Administration of methadone alone resulted in a significant reduction in the duration of hind limb extension (HLE) than that in the control group. Methadone pretreatment at doses of 0.1 and 0.3 mg/kg i.p. decreased, and at doses of 1 and 3 mg/kg i.p. had an increasing effect on anticonvulsant efficacy of gabapentin. Pretreatment with all doses of methadone significantly decreased the valproate anticonvulsive efficacy. At doses of 1 and 3 mg/kg i.p. methadone per se increased brain MDA levels after MES-induced seizure. Administration of methadone (0.3 mg/kg i.p.) enhanced and at 3 mg/kg decreased gabapentin effect on brain MDA level, but their co-treatment did not lead to further increase in MDA. Methadone at 0.3–3 mg/kg enhanced the effect of sodium valproate on MDA levels in the brain, but at all doses significantly potentiated its effect on brain TNF-α levels. The drugs did not produce any side effects on motor coordination in experimental animals. In conclusion, methadone showed different effects on anticonvulsant actions of gabapentin and valproate through regulation of brain levels of MDA and TNF-α.

Lepidium meyenii Walp (red maca) Supplementation Prevents Acrylamide-Induced Oxidative Stress and Liver Toxicity in Rats: Phytochemical Composition by UHPLC-ESI-MS/MS.

Lepidium meyenii Walp (red maca) is a high Andean plant cultivated since the Incas and has innumerable therapeutic properties. The study aims to identify its phytochemical composition using UHPLC-ESI-MS/MS, and evaluate its effects on acrylamide-induced oxidative stress. The lyophilized aqueous extract of red maca (LAqE-RM) was orally administered in doses of 1 and 2g/kg body weight for 4weeks. Malondialdehyde (MDA) levels in erythrocytes, brain, and liver, as well as hepatic levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Administration of acrylamide for 2 and 4weeks significantly increased (p < 0.001) MDA levels in erythrocytes, brain, and liver. However, LAqE-RM prevented (p < 0.001) an increase in MDA levels in all tissues studied. Likewise, the groups treated with LAqE-RM presented significantly (p < 0.001) lower levels of ALT and AST compared to the control. Treatment with LAqE-RM ameliorated the acrylamide-induced oxidative stress by reducing MDA levels in erythrocytes, brain, and liver and by lowering liver levels of ALT and AST in a dose-dependent manner. Twenty-five secondary metabolites were identified and characterized from LAqE-RM based on UHPLC mass spectrophotometry. These include carbolines, alkamides, fatty acids, and macamides, which are probably involved in their antioxidant protective role.

The Anti-obesity Agent d-norpseudoephedrine Protects Against Rotenone-induced Parkinson’s Disease in Mice

The effect of the ephedrine derivative D-norpseudoephedrine on rotenone-induced Parkinson’s disease in mice was studied. Mice received subcutaneous injections of rotenone (1.5 mg/kg, every other day for two weeks) and were treated with the vehicle, L-dopa (25 mg/kg) or pseudoephedrine at doses of 1.8, 5.4 and 10.8 mg/kg once daily orally. Brain levels of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) were determined and histopathological study of the brain was done. Motor testing included stair, wire hanging and wood walking tests. Results indicated that ompared with vehicle controls, rotenone caused significant increases in brain MDA and NO along with GSH depletion. Rotenone impaired neuromuscular strength, and motor balance and coordination. There were also marked decrease in size and number of substantia nigra pigmented cells and deeply stained neurons and karyorrhexis in the cerebral cortex and hippocampus. Treatment with pseudoephedrine reduced brain MDA, NO and increased GSH levels and improved motor performance. Furthermore, pseudoephedrine prevented substantia nigra dopaminergic cell death and neurodegeneration in the cortex and hippocampus brain regions in a dose-dependent manner. These data suggest that pseudoephedrine might prove of benefit adjunctive therapy of Parkinson’s disease.

Ameliorating Effect of Morin Hydrate on Chronic Restraint Stress-induced Biochemical Disruption, Neuronal, and Behavioral Dysfunctions in BALB/c Mice.

Morin hydrate (MH) is a bioflavonoid component of many fruits and vegetables. Our previous research demonstrated that MH provides neuroprotection in mouse models of acute restraint stress and sleep deprivation by attenuating hippocampal neuronal damage and enhancing memory. Based on these findings, our study investigated the role of MH in chronic stress-induced neuronal and biochemical perturbations in BALB/c mice. Male BALB/c mice were divided into 6 groups (n=6). Groups 1 and 2 received vehicle (10 mL/kg normal saline), groups 3-5 received MH (5, 10, 20 mg/kg IP), while group 6 received ginseng (25 mg/kg) daily and 30 minutes afterward were restrained in a plastic cylindrical restrainer for 14 days. Immobility time in the forced swim test increased in the MH-treated group, indicating an antidepressant-like effect. Also, a reduction in frequency and duration of open arms exploration was observed in the elevated plus-maze (EPM) test in stressed mice, and administration of MH (5, 10, 20 mg/kg, IP) reversed these effects. An increase in blood levels of glucose, triglycerides, total cholesterol, and brain malondialdehyde and nitrite levels was observed in the stressed groups, which was reversed by MH. Furthermore, MH reversed the stress-induced reduction in HDL cholesterol and glutathione (GSH) levels and attenuated stress-induced alterations in the prefrontal cortex and hippocampus. Our findings suggest that MH attenuated chronic restraint stress-behavioral and biochemical perturbations, probably due to its capability to decrease oxidative stress and brain neuronal damage. Chronic stress perturbs physiological and psychological homeostasis;Morin hydrate normalized chronic stress-induced biochemical disruptions;Morin hydrate attenuated structural changes in prefrontal cortex and hippocampus. Stress is a state of being overwhelmed by demands exceeding the personal and social means of coping. Exposure to excessive stress has resulted in disruption of neurochemical and physiological processes, which sometimes manifest as behavioural abnormalities. Therefore to cope with the stressful life style, there is need to develop a therapeutic agent of plant origin. Morin hydrate is a flavonoid with known antioxidant and neuroprotective properties; however, its effect in a stressful condition has not been studies. The study thus evaluated ameliorating effect of Morin hydrate on chronic restraint stress-induced biochemical disruption, neuronal and behavioral dysfunctions in BALB/c mice. To achieve this, mice were exposed to chronic restraint stress protocol for fourteen days. Behavioural changes were examined using various techniques. The vital parameters like antioxidant, glucose and nitrite levels were also taken. Our findings show that Morin hydrate prevented behavioral abnormalities and damage to the brain cells. It also inhibited stress-induced biochemical disturbance.

Mechanistic Insights into Ameliorating Effect of Geraniol on d-Galactose Induced Memory Impairment in Rats

Geraniol (GE), an important ingredient in several essential oils, displayed pleiotropic biological activities through targeting multiple signaling cascades. In the current study, we aimed to examine the protective effect of GE on d-galactose (d-gal) induced cognitive impairment and explore the underlying mechanisms. Forty male Wistar rats (8 weeks old) were randomly categorized into 4 groups; Group I (saline + vehicle [edible oil]), group II (saline + geraniol) (100 mg/kg/day orally), group III (d-galactose) (100 mg/kg/day subcutaneously injected), and group IV (d-galactose + geraniol). Behavioral impairments were evaluated. Brain levels of malondialdehyde (MDA) and reduced glutathione (GSH) as well as superoxide dismutase (SOD) and acetylcholinesterase (AchE) activities were estimated. The levels of inflammatory markers [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and nuclear factor kappa beta (NF-kβ)], endoplasmic reticulum stress sensors [inositol requiring protein 1(IRE1) and protein kinase RNA–like endoplasmic reticulum kinase (PERK)], brain-derived neurotrophic factor (BDNF), and mitogen-activated protein kinases (MAPK) pathway were measured by ELISA. Also, hippocampal histopathological assessment and immunohistochemical analysis of glial fibrillary acidic protein (GFAP) and caspase-3 were performed. Glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) mRNA expression and protein levels were assessed. GE effectively ameliorated aging-related memory impairment through increasing GSH, BDNF, Ach levels, and SOD activity. Additionally, GE treatment caused a decrease in the levels of MDA, inflammatory mediators, and ER stress sensors as well as the AchE activity together with concomitant down-regulation of GRP78 and CHOP mRNA expression. Moreover, GE improved neuronal architecture and rat's spatial memory; this is evidenced by the shortened escape latency and increased platform crossing number. Therefore, GE offers a unique pharmacological approach for aging-associated neurodegenerative disorders.Graphical

Combination of magnesium supplementation with treadmill exercise improves memory deficit in aged rats by enhancing hippocampal neurogenesis and plasticity: a functional and histological study.

This study aimed to investigate the possible ameliorative effects of co-supplementation with Mg2+ and treadmill exercise on memory deficit in aged rats. Fifty male albino rats (10 young and 40 aged rats) were divided into 5 groups (10 rats/group): young, aged sedentary, aged exercised, aged Mg2+-supplemented, and aged exercised and Mg2+-supplemented. Memory was assessed using the Y-maze and novel object recognition tests. Plasma samples were collected for measurement of C-reactive protein (CRP). Subsequently, brain malondialdehyde and catalase levels were measured. Histological and immunohistochemical analyses of the hippocampi were performed. Our results showed impaired memory in aged sedentary rats, with significantly elevated plasma CRP and brain malondialdehyde levels and decreased brain catalase. The hippocampus of aged sedentary rats showed cellular degeneration, downregulation of synaptophysin (SYP) and proliferating cell nuclear antigen (PCNA), and upregulation of glial fibrillary acidic protein (GFAP) and caspase-3. Mg2+ supplementation and/or treadmill exercise significantly improved memory tests in aged rats, which could be explained by the upregulation of hippocampal SYP and PCNA expression and downregulation of GFAP and caspase-3 expression with antioxidant and anti-inflammatory mechanisms. The combined therapy had a better effect than both treatments alone, confirming the role of Mg2+ supplementation with physical exercise in enhancing age-related memory deficit. Novelty: Magnesium supplementation with treadmill exercise improves memory deficit in aged rats. The possible mechanisms are upregulation of the hippocampal synaptophysin and PCNA, downregulation of GFAP and caspase-3, the antioxidant and anti-inflammatory mechanisms.

Experimental validation of Vitex negundo leaves hydroalcoholic extract for neuroprotection in haloperidol induced parkinson's disease in rat.

Parkinsonism is a neurodegenerative disease, mainly imbalance in dopamine and acetylcholine neurotransimitter in mid brain, which manifestation of dysfunctions of extrapyramidal like akinesia, tremor, rigidity and catalepsy etc., even cognitive and memory loss. The current study is framed to evaluate the effect of Vitex negundo (VNL) leaf extract in Haloperidol induced PD in rats. In vitro studies of antioxidant capacity were checked via DPPH and NO assays and identified its Acetylcholinesterase (AChE) inhibitory activity. Secondly the In vivo study of anti-PD activity in Haloperidol induced in rats were evaluated by Rotarod, morris water maze (MWM), cooks pole climb (CPC), actophotometer, novel object recognition (NOR), and T-maze were utilized to assess extrapyramidal, cognitive and memory function. Thirdly, changes in biomarker level viz. (AChE), butyrylcholinesterase. (BChE) in hippocampus and cortex, reduced glutathione (GSH), malondialdehyde (MDA), total protein (TP), superoxide dismutase (SOD), catalase (CAT), and dopamine level in the whole brain were measured. Finally, histopathology of hippocampus and cortex was examined at 40x magnification to access restoring integrity and maintaining the architecture of neuronal cell in the treatment group compared to control group and L-DOPA as a standard treatment group. V. negundo showed potent antioxidant potency on scavenging of DPPH (IC50 84.81μg/ml) and NO (IC50 133.20μg/ml) and possess AChE inhibitory potency (IC50 114.35μg/ml) by in vitro studies. The Rotarod, MWM, CPC, Actophotometer, NOR, T-maze demonstrated that Haloperidol group administration declines performance time, ELT, TL and decreases locomotion, cognitive and memory respectively. The treatment of VNL 100, 200, and 400mg/kg p.o. significantly (p < 0.05 to p < 0.0001) reversed. Whole brain AChE, BChE, and MDA level were significantly raised and GSH, TP, SOD, CAT and Dopamine were significantly declined in Haloperidol treated group rats, especially V. negundo 400mg/kg p.o. highly significantly ameliorate the Haloperidol group altered pathological changes through the restoration of the cholinergic function, enhancing the antioxidant defense and by increasing the dopaminergic function. The current study provides validation of V. negundo for its anti-PD activity and could be a valuable source for the treatment of PD in future.

Cognitive enhancement and neuroprotective effects of OABL, a sesquiterpene lactone in 5xFAD Alzheimer's disease mice model

Alzheimer's disease (AD) is a neurodegenerative disease in which oxidative stress and neuroinflammation were demonstrated to be associated with neuronal loss and cognitive deficits. However, there are still no specific treatments that can prevent the progression of AD. In this study, a screening of anti-inflammatory hits from 4207 natural compounds of two different molecular libraries indicated 1,6-O,O-diacetylbritannilactone (OABL), a 1,10-seco-eudesmane sesquiterpene lactone isolated from the herb Inula britannica L., exhibited strong anti-inflammatory activity in vitro as well as favorable BBB penetration property. OABL reduced LPS-induced neuroinflammation in BV-2 microglial cells as assessed by effects on the levels of inflammatory mediators including NO, PGE2, TNF-α, iNOS, and COX-2, as well as the translocation of NF-κB. Besides, OABL also exhibited pronounced neuroprotective effects against oxytosis and ferroptosis in the rat pheochromocytoma PC12 cell line. For in vivo research, OABL (20 mg/kg B.W., i.p.) for 21 d attenuated the impairments in cognitive function observed in 6-month-old 5xFAD mice, as assessed with the Morris water maze test. OABL restored neuronal damage and postsynaptic density protein 95 (PSD95) expression in the hippocampus. OABL also significantly reduced the accumulation of amyloid plaques, the Aβ expression, the phosphorylation of Tau protein, and the expression of BACE1 in AD mice brain. In addition, OABL attenuated the overactivation of microglia and astrocytes by suppressing the expressions of inflammatory cytokines, and increased glutathione (GSH) and reduced malondialdehyde (MDA) and super oxide dismutase (SOD) levels in the 5xFAD mice brain. In conclusion, these results highlight the beneficial effects of the natural product OABL as a novel treatment with potential application for drug discovery in AD due to its pharmacological profile.

Effect of MCI-186 on Lipid Peroxidation in Experimental Traumatic Brain Damage in Rats.

Brain damage occurs in many clinical conditions, including trauma, ischemia, and hypertension. Reactive oxygen products and lipid peroxidation are responsible for the brain damage that occurs in these clinical conditions. We investigated whether MCI-186 (3-methyl-1-phenyl-2-pyrazoline-5-one), a free radical binding agent on lipid peroxidation, affects malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GPx) levels in traumatic brain damage. The traumatic brain damage model, modified by Feeney, was performed on 28 male Wistar rats separated into 4 groups. The MDA, GSH, and GPx levels in the brain tissues of each group were studied. MDA levels in the traumatized group were significantly higher than those in the sham and MCI-186 groups (p<0.05), while GSH levels were significantly higher in the sham group than in the trauma and solvent groups (p<0.05). No significant difference was observed between the sham and MCI-186 groups (p>0.05). Although the average GPx level was higher in the sham and MCI-186 groups, no significant difference was found between groups. Reactive oxidation products significantly decreased in the MCI-186 group. Thus, MCI-186 can be used as a free radical-binding agent in traumatic brain damage.

Histopathological evaluation of IBA-1, GFAP activity in the brain cortex of rats administered cadmium chloride.

Purpose: This study aims to evaluate the changes in brain tissue and blood-brain barrier due to oxidative stress during cadmium (Cd) poisoning by biochemical, histopathological, and immunohistochemical methods. Methods: 170-190 g weighing eight-week-old female Wistar albino rats were divided into two groups (control and experimental), with 7 animals in each group. Experimental group rats were given 2 mg/kg/day powdered cadmium chloride dissolved in water intraperitoneally every day for two weeks. Biochemical, histopathological and immunohistochemical examination was performed. Results: It was seen that brain malondialdehyde (MDA) levels increased significantly, and glutathione (GSH) and catalase (CAT) activity levels decreased. In addition to degeneration in some pyramidal cells and glial cells, deformity, and picnosis in the nucleus, dilation of the meninges and cortex vessels, and inflammation around the blood vessels were observed. An increase was found in ionized calcium binding adaptor molecule 1 (IBA-1) expression in microglia cells and degenerative endothelial cells, and increased glial fibrillary acidic protein (GFAP) expression was observed in astrocytes and degenerate neurons. Conclusions: It has been shown that cadmium toxicity may cause microgliosis and astrogliogenesis by inducing cytokine production due to cell degeneration, vascularity, and inflammation in the brain cortex and by affecting microglia, astrocytes cells.

Cowpea (Vigna unguiculata) Extract Reduce Malondialdehyde Levels and Prevent Aortic Endothelial Cell Decline in Ovariectomized Rats

Estrogen has anti-oxidative and anti-inflammatory properties, but its levels decrease in postmenopausal women who can trigger oxidative stress. One of the most damaging effects of ROS is lipid peroxidation, and the end product is Malondialdehyde (MDA). Similarly, aging endothelium has increased oxidative stress and endothelial cell sensitivity to apoptosis. This study aimed to determine the effect of cowpea extract on serum MDA levels, aortic endothelial cell counts, and brain MDA levels in the ovariectomy model. Cowpea extract can be used as an alternative to prevent and overcome the effects that occur during menopause, such as cardiovascular problems, decreased bone mineral density, and dementia. The study used 15-month-old female Rattus norvegicus, divided into six groups (OVX, SHAM, OVX+estradiol, OVX+Vu 1.25; 2.5; and 5 mg/kg BW/day). Serum and brain MDA levels were examined by ELISA method, while the number of aortic endothelial cells were examined on histopathological preparations with Hematoxylin &amp; Eosin (HE) staining. The mean value of serum and brain MDA levels decreased with an increase in the dose given (p-value 0.016). The mean value of aortic endothelial cells between the dose groups did not significantly differ. However, the mean value showed an increasing trend as the dose of cowpea extract was given. The results of this study indicate that the extract of cowpea has the potential as an antioxidant to reduce serum and brain MDA levels, prevent a decrease in the number of aortic endothelial cells. As prevention, cowpea extract can be used as an antioxidant and consumed since premenopause to minimize problems that occur during postmenopause.

Dihydromyricetin Improves Cognitive Impairments in d-Galactose-Induced Aging Mice through Regulating Oxidative Stress and Inhibition of Acetylcholinesterase.

Alzheimer's disease (AD) is a neurodegenerative disease with phenomena of cognitive impairments. Oxidative stress and cholinergic system dysfunction are two widely studied pathogenesis of AD. Dihydromyricetin (DMY) is a natural dihydroflavonol with many bioactivities. In this study, it is aimed to investigate the effects of DMY on cognitive impairment in d-galactose (d-gal) induced aging mice. Mice are intraperitoneally injected with d-gal for 16 weeks, and DMY is supplemented in drinking water. The results show that DMY significantly improves d-gal-induced cognitive impairments in novel object recognition and Y-maze studies. H&E and TUNEL staining show that DMY could improve histopathological changes and cell apoptosis in mice brain. DMY effectively induces the activities of catalase, superoxide dismutase and glutathione peroxidase, and reduces malondialdehyde level in mice brain and liver. Furthermore, DMY reduces cholinergic injury by inhibiting the activity of Acetylcholinesterase (AChE) in mice brain. In vitro studies show that DMY is a non-competitive inhibitor of AChE with IC50 value of 161.2µgmL-1 . DMY alleviates the cognitive impairments in d-gal-induced aging mice partly through regulating oxidative stress and inhibition of acetylcholinesterase.

Ameliorating effect of continuous alpha-glycosyl isoquercitrin treatment starting from late gestation in a rat autism model induced by postnatal injection of lipopolysaccharides

The present study investigated the role of neuroinflammation and brain oxidative stress induced by neonatal treatment with lipopolysaccharides (LPS) on the development of autism spectrum disorder (ASD)–like behaviors and disruptive hippocampal neurogenesis in rats by exploring the chemopreventive effects of alpha-glycosyl isoquercitrin (AGIQ) as an antioxidant. AGIQ was dietary administered to dams at 0.25% or 0.5% (w/w) from gestational day 18 until postnatal day (PND) 21 on weaning and then to pups until the adult stage on PND 77. The pups were intraperitoneally injected with LPS (1 mg/kg body weight) on PND 3. At PND 6, LPS alone increased Iba1+ and CD68+ cell numbers without changing the CD163+ cell number and strongly upregulated pro-inflammatory cytokine gene expression (Il1a, Il1b, Il6, Nfkb1, and Tnf) in the hippocampus, and increased brain malondialdehyde levels. At PND 10, pups decreased ultrasonic vocalization (USV), suggesting the induction of pro-inflammatory responses and oxidative stress to trigger communicative deficits. By contrast, LPS alone upregulated Nfe2l2 expression at PND 6, increased Iba1+, CD68+, and CD163+ cell numbers, and upregulated Tgfb1 at PND 21, suggesting anti-inflammatory responses until the weaning period. However, LPS alone disrupted hippocampal neurogenesis at weaning and suppressed social interaction parameters and rate of freezing time at fear acquisition and extinction during the adolescent stage. On PND 77, neuroinflammatory responses had mostly disappeared; however, disruptive neurogenesis and fear memory deficits were sustained. AGIQ ameliorated most changes on acute pro-inflammatory responses and oxidative stress at PND 6, and the effects on USVs at PND 10 and neurogenesis and behavioral parameters throughout the adult stage. These results suggested that neonatal LPS treatment induced acute but transient neuroinflammation, triggering the progressive disruption of hippocampal neurogenesis leading to abnormal behaviors in later life. AGIQ treatment was effective for ameliorating LPS-induced progressive changes by critically suppressing initial pro-inflammatory responses and oxidative stress.

Syringic Acid Reversed Depression-Resembling Behavior Induced by Chronic Unpredictable Mild Stress Paradigm in Mice

The aim of the present investigation was to explore the anti-depressive potential of syringic acid in Swiss albino male mice. Mice were exposed to unpredictable stress for 21 sequential days. Imipramine (15 mg/kg, p.o.) and syringic acid (10 and 20 mg/kg, p.o.) were administered for three consecutive weeks to unstressed and stressed mice. Tail suspension test and sucrose preference test were used to evaluate antidepressant potential of the drugs. Syringic acid and imipramine significantly decreased immobility periods of stressed mice as compared to vehicle treated stressed mice in tail suspension test, indicating their antidepressant effects. Syringic acid (20 mg/kg) and imipramine also significantly restored the reduced sucrose preference (%) in stressed mice, which further substantiated their antidepressant effects. Syringic acid and imipramine did not produce significant antidepressant effects in unstressed mice. These drugs did not significantly affect locomotor activity scores of mice. Syringic acid (20 mg/kg) and imipramine significantly reversed chronic unpredictable mild stress (CUMS)-induced increase of plasma nitrite and corticosterone levels; brain malondialdehyde levels and monoamine oxidase (MAO(-A activity. Both the drugs also significantly reversed CUMS-induced decrease in brain reduced glutathione levels and catalase activity. Thus, syringic acid showed significant antidepressant-like activity in mice subjected to CUMS through alleviation of oxidative and nitrosative stress; and inhibition of brain MAO-A activity. Further, antidepressant-like activity of syringic acid in mice subjected to CUMS might also be due to decrease in plasma corticosterone levels. Fig. 1 Illustrates further the scheme of protocol designed with various groups of animals.

Brain Levels of Reduced Glutathione and Malondialdehyde in Honey-Fed Wistar Rats

This research sought to verify the effect of natural honey on brain levels of malondialdehyde (MDA) and reduced glutathione (GSH) in rats. Forty nine male and female Wistar rats were used for the experiment. The rats were allotted into seven groups of seven rats in each group. For one month, rats in groups 1-4 were fed with 100% feed, 20%, 30% and 40% honey respectively. The remaining 3 groups were fed with amounts of refined fructose and glucose equivalent to those in 20%, 30% and 40% honey. The brains were then excised, homogenized and used for biochemical analysis. Results showed that honey in all concentrations caused a significant increase in GSH levels but only 20% honey caused a significant decrease in MDA level when compared with control. Also, fructose feeding at 20%, 30% and 40% increased both brain GSH and MDA levels. Consequently, the influence of GSH as an antioxidant against brain lipid peroxidation needs further studies for better understanding since an increase in GSH for fructose- and honey-fed rats did not cause a simultaneous decrease in MDA content.

Oral Exposure to Tributyltin Induced Behavioral Abnormality and Oxidative Stress in the Eyes and Brains of Juvenile Japanese Medaka (Oryzias latipes).

The widely used compound tributyltin (TBT), which can be continuously detected in aquatic species and seafood, may induce diverse adverse effects on aquatic organisms. However, little is known regarding the mechanistic links between behavioral abnormality and oxidative stress in different fish tissues in response to oral TBT exposure. Herein, juvenile Japanese medaka (Oryzias latipes) were orally exposed to TBT at 1 and 10 ng/g-bw/d for four weeks. After exposure, the locomotor activity and social interaction of juvenile medaka were found to be significantly reduced in the 10 ng/g-bw/d TBT-exposed group. Furthermore, the antioxidant biomarkers in different tissues of juvenile medaka showed different levels of sensitivity to TBT exposure. The eye superoxide dismutase (SOD) activities markedly increased in both groups exposed to 1 and 10 ng/g-bw/d TBT, while the eye and brain malondialdehyde (MDA) levels increased in the higher dose group. Furthermore, the eye and brain ATPase activities markedly declined in the 1 ng/g-bw/d TBT-exposed group. A correlation analysis revealed that the decreased locomotor activity and social interaction in medaka were associated with the eye antioxidant enzyme (i.e., SOD and catalase (CAT)) activity and brain oxidative damage level. Thus, our findings suggested that there might be some mechanistic links between the behavioral abnormality induced by TBT exposure and oxidative stress in the eyes and brains of medaka. Thus, our findings indicate that the impacts of oral exposure to TBT should be considered to better assess its risk to the aquatic ecosystem and human health.

Lycopene ameliorates propionic acid-induced autism spectrum disorders by inhibiting inflammation and oxidative stress in rats.

This study was conducted to study lycopene efficacy in brain-behavior, pro-inflammatory and apoptotic markers, and antioxidant levels in a rodent model. Rats were administered with propionic acid (PPA) (500mg/kg BW) to induce autism-like disorders, then treated with different lycopene (L) concentrations (5, 10, 20mgkg-1 day-1 ) for 35days. The groups were: (i);control, (ii);PPA, (iii);PPA + L5, (iv);PPA + L10, and (v);PPA + L20. In this study, serum and brain malondialdehyde (MDA) levels decreased with lycopene supplements compared to the PPA group, similarly to the brain levels of inflammatory factors (IL-1α, IL-8, NF-κB, TNF-α; p<.05). Besides, brain levels of anti-apoptotic Bcl-2 decreased, whereas pro-apoptotic Bax, antioxidant Nrf2, and HO-1 levels in brain increased compared with PPA (p<.05). This study showed that lycopene might have therapeutic value to improve the dysfunctions in learning and memory in a dose-dependent way, along with the antioxidant, anti-inflammatory, and antiapoptotic molecular responses in a rat model of ASD-like disorders. PRACTICAL APPLICATIONS: This study suggested that lycopene can reduce propionic acid (PPA)-induced learning and memory impairment and oxidative damage by participating in multiple biological activities such as antioxidant, and anti-inflammatory effects. Lycopene protects serum and brain tissues against PPA induced oxidative damage in rats. These effects may be realized through up-regulation of the brain Nrf2/HO-1 pathway and down-regulation of the IL-1α, IL-8, TNF-α, and NF-κB levels. Lycopene may also contribute to memory and learning function, apoptotic/antiapoptotic modulation, and antioxidant and possible therapeutic efficacy in PPA-induced- Autism spectrum disorder cases.