Geraniol mitigates anxiety-like behaviors in rats by reducing oxidative stress, repairing impaired hippocampal neurotransmission, and normalizing brain cortical-EEG wave patterns after a single electric foot-shock exposure.

Anxiety-like conditions can interfere with daily activities as the adaptive mechanism fails to cope with stress. These conditions are often linked with increased oxidative stress, and abrupt neurotransmission and electroencephalography (EEG) wave pattern. Geraniol, a monoterpenoid, has antioxidant and anti-inflammatory activities, as well as brain-calming effects. Therefore, in this study, geraniol was tested for the potential anxiolytic effects in a rat model of anxiety. The rats were exposed to an electric foot shock (1 mA for 1 s) to develop anxiety-like symptoms. Treatment was carried out using geraniol (10 and 30 mg/kg) and the standard diazepam drug. The behavior of the rats was analyzed using the open field test, light-dark test, and social interaction test. Afterward, the rats were decapitated to collect samples for neurochemical and biochemical analyses. The cortical-EEG wave pattern was also obtained. The study revealed that the electric foot shock induced anxiety-like symptoms, increased oxidative stress, and altered hippocampal neurotransmitter levels. The power of low-beta and high-beta was amplified with the increased coupling of delta-beta waves in anxiety group. However, the treatment with geraniol and diazepam normalized cortical-EEG wave pattern and hippocampal serotonin and catecholamines profile which was also reflected by reduced anxious behavior and normalized antioxidant levels. The study reports an anxiolytic potential of geraniol, which can be further explored in future.

Renal protection by ellagic acid in a rat model of glycerol-induced acute kidney injury.

Studies conducted on animal models have shown that the administration of glycerol can lead to kidney tissue damage and impaired renal function. This is believed to be caused by oxidative stress and inflammation, which in turn can result in elevated levels of blood urea nitrogen (BUN) and creatinine. These metabolites are commonly used as indicators of renal function. The aim of the current experimental research was to investigate the protective efficacy of ellagic acid in a rat model of rhabdomyolysis induced by glycerol. Sixty healthy adult male Wistar rats weighing between 250 - 300 g were divided into five equal groups including control, rhabdomyolysis (administered 8.00 mL kg-1 of glycerol), and three rhabdomyolysis plus various doses of ellagic acid (25.00, 50.00 and 100 mg kg-1 per day; 72 hr after receiving glycerol for 14 days successively) groups. Serum levels of BUN, creatinine, lactate dehydrogenase, alkaline phosphatase, electrolytes and inflammatory cytokines were evaluated in all rats. Histopathological studies were also performed on kidney tissues from all groups. The administration of ellagic acid resulted in a significant increase in renal function biomarkers compared to the rats with acute kidney injury. This increase was consistent with notable reductions in tumor necrosis factor-α levels and increases in interleukin-10 levels observed in blood samples. Furthermore, the improvement in histopathological indices observed in rats received ellagic acid confirmed its nephroprotective role. The results of the current experimental study suggest that ellagic acid can improve kidney damage following glycerol injection, potentially by modulating the inflammatory process.

The protective effects of gallic acid and SGK1 inhibitor on cardiac damage and genes involved in Ca2+ homeostasis in an isolated heart model of ischemia/reperfusion injury in rat.

Serum and glucocorticoid-induced kinase 1 (SGK1) is an enzyme that may play a vital role in myocardial ischemia/reperfusion (I/R) injury. This enzyme may affect sarcoplasmic reticulum Ca2+ ATPase (SERCA2), ryanodine receptor (RyR2) and sodium/calcium exchanger (NCX1) during myocardial ischemia/reperfusion injury. The objective of this investigation was to analyze the effects of the combination of GSK650394 (SGK1 inhibitor) and gallic acid on the calcium ions regulation, inflammation, and cardiac dysfunction resulting from ischemia/reperfusion (I/R) injury in the heart. Sixty male Wistar rats were randomly divided into six groups, pretreated with gallic acid or vehicle for 10 days. Then the heart was isolated and exposed to I/R. In the SGK1 inhibitor groups, GSK650394 was infused 5 min before ischemia induction. After that, Ca2+ homeostasis, inflammatory factors, cardiac function, antioxidant activity, and myocardial damage were evaluated. The findings suggested that the use of two drugs in combination therapy produced more significant improvements in left ventricular end diastolic pressure, left ventricular systolic pressure, RR-interval, ST-elevation, inflammation factors, and antioxidant enzymes activity as compared to the use of each drug. Despite this, there was a significant decrease observed in heart marker enzymes (including lactate dehydrogenase (LDH), troponin-I (cTn-I), creatine kinase-MB (CK-MB) and creatine phosphokinase (CPK) when compared to the ischemic group. Additionally, the expression of RyR2, NCX1, and SERCA2 genes showed a noteworthy increase as compared to the ischemic group. The findings of this study propose that using both of these agents on myocardial I/R injury could have superior advantages compared to using only one of them.

Sesamin mitigates lead-induced behavioral deficits in male rats: The role of oxidative stress.

Lead (Pb) is a well-known toxic pollutant that has negative effects on behavioral functions. Sesamin, a phytonutrient of the lignan class, has shown neuroprotective effects in various neurological disorder models. The present study was undertaken to evaluate the putative protective effects of sesamin against Pb-induced behavioral deficits and to identify the role of oxidative stress in male rats. The rats were exposed to 500 ppm of Pb acetate in their drinking water and simultaneously treated orally with sesamin at a dose of 30 mg/kg/day for eight consecutive weeks. Standard behavioral paradigms were used to assess the behavioral functions of the animals during the eighth week of the study. Subsequently, oxidative stress factors were evaluated in both the cerebral cortex and hippocampal regions of the rats. The results of this study showed that Pb exposure triggered anxiety-/depression-like behaviors and impaired object recognition memory, but locomotor activity was indistinguishable from the normal control rats. These behavioral deficiencies were associated with suppressed enzymatic and non-enzymatic antioxidant levels, and enhanced lipid peroxidation in the investigated brain regions. Notably, correlations were detected between behavioral deficits and oxidative stress generation in the Pb-exposed rats. Interestingly, sesamin treatment mitigated anxio-depressive-like behaviors, ameliorated object recognition memory impairment, and modulated oxidative-antioxidative status in the rats exposed to Pb. The results suggest that the anti-oxidative properties of sesamin may be one of the underlying mechanisms behind its beneficial effect in ameliorating behavioral deficits associated with Pb exposure.

Ellagic acid alleviates motor, cognitive and hippocampal electrical activity deficits in the male rats with 2-vessel occlusion cerebral ischemia/reperfusion.

Objective: Cerebral ischemia/reperfusion (I/R) has been known as a major cause of inability and mortality worldwide. Ellagic acid (EA) has many pharmacological effects including antioxidant, antithrombotic and neurorestoration activities. The aim of this study was evaluation of the effects of EA on motor and cognitive behaviors, hippocampal local field potential (LFP), brain oxidative stress in male rats with cerebral 2-vessel occlusion ischemia/reperfusion (2VO I/R). Materials and Methods: Forty-eight male Wistar rats (250-300 g) were assigned into six groups. 1) The Sham: rats were treated with DMSO10%/normal saline as solvent of EA 3 times daily for 1 week; 2) I/R+Veh; I/R rats received vehicle; 3-5) EA-treated groups: I/R rats received 50, 75, or 100 mg/kg EA; and 6) Cont+EA100: intact rats received EA. The cerebral 2VO I/R was made by the bilateral common carotid arteries closing for 20 min followed by reperfusion. The behavioral tests and hippocampal LFP recording were performed after treatment with EA. The oxidative stress parameters were assayed by special ELISA kits. Results: Cerebral 2VO I/R significantly decreased motor coordination, memory and hippocampal LFP and significantly increased oxidative stress. Treatment with EA improved all I/R complications. Conclusion: The current findings showed that treatment of I/R rats with EA could reverse cognitive and motor functions, and improve the LFP and oxidative stress markers. So, effects of EA on cognitive and motor function may at least in part, be due to its antioxidative actions.

Anandamide Attenuates Neurobehavioral Deficits and EEG Irregularities in the Chronic Sleep Deprivation Rats: The Role of Oxidative Stress and Neuroinflammation.

Sleep deprivation increases stress, anxiety, and depression by altering the endocannabinoid system's function. In the present study, we aimed to investigate the anti-anxiety and anti-depressant effects of the endocannabinoid anandamide (AEA) in the chronic sleep deprivation (SD) model in rats. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation + 20 mg/kg AEA (SD + A). The rats were kept in a sleep deprivation device for 18 h (7 to 1 a.m.) daily for 21 days. Open-field (OFT), elevated plus maze, and forced swimming tests (FST) were used to assess anxiety and depression-like behavior. As well as the cortical EEG, CB1R mRNA expression, TNF-α, IL-6, IL-4 levels, and antioxidant activity in the brain were examined following SD induction. AEA administration significantly increased the time spent (p < 0.01), the distance traveled in the central zone (p < 0.001), and the number of climbing (p < 0.05) in the OFT; it also increased the duration and number of entries into the open arms (p < 0.01 and p < 0.05 respectively), and did not reduce immobility time in the FST (p > 0.05), AEA increased CB1R mRNA expression in the anterior and medial parts of the brain (p < 0.01), and IL-4 levels (p < 0.05). AEA also reduced IL-6 and TNF-α (p < 0.05) and modulated cortical EEG. AEA induced anxiolytic-like effects but not anti-depressant effects in the SD model in rats by modulating CB1R mRNA expression, cortical EEG, and inflammatory response.

Anethole attenuates motor dysfunctions, striatal neuronal activity deficiency and blood brain barrier permeability by decreasing striatal α-synuclein and oxidative stress in rotenone-induced Parkinson's disease of male rats.

INTRODUCTION: Anethole is the main compound of the essential oil of anise and several other plants, which has antioxidant, anti-inflammatory, and neuroprotective properties. Oxidative stress is considered as an important factor in the pathogenesis of PD. In the present study, we aimed to investigate the effects of anethole against rotenone-induced PD. METHODS: Male Wistar rats were randomly divided into six groups. Control group received DMSO + sunflower oil, model group received rotenone (2 mg/kg, s.c, daily for 35 days), positive control group received L-Dopa, and test groups received anethole (62.5, 125, and 250 mg/kg, i.g, daily for 35 days) 1 hour before each rotenone injection. Body weight changes, rotarod test, stride length test, and extracellular single unit recording were performed after treatment. After behavioral test, Brain water content and blood brain barrier (BBB) permeability were evaluated, and the levels of malondialdehyde (MDA), superoxide dismutases (SOD), alpha-synuclein and MAO-B were measured in the striatum. RESULTS: Chronic administration of rotenone induced body weight loss and caused significant dysfunction in locomotor activity, neuronl firing rate, and BBB. Rotenone also decreased SOD activity, increased MDA level, and elevated the expression of alpha-synuclein and MAO-B in the striatum. However, treatment with anethole attenuated body weight loss, motor function, neuronal activity, and BBB function. Furthermore, Anethole treatment attenuated oxidative stress and decreased the expression of alpha-synuclein and MAO-B compared to the rotenone group. CONCLUSION: Our results show that through its antioxidant properties, aethole can improve the cellular, molecular and behavioral characteristics of rotenone-induced Parkinson's disease.

Possible mechanisms involved in the neuroprotective effects of chrysin against mild traumatic brain injury-induced spatial cognitive decline: An in vivo study in a rat model.

Traumatic brain injury (TBI) is recognized as an important risk factor for cognitive deficits. The present study was designed to determine the potential neuroprotective effects of chrysin, a natural flavonoid compound, against TBI-induced spatial cognitive decline and the possible mechanisms involved. Oral administration of chrysin (25, 50, or 100 mg/kg/day) was initiated in rats immediately following the induction of the diffuse TBI model using the weight-dropping Marmarou model. Spatial cognitive ability, hippocampal synaptic plasticity, blood-brain barrier (BBB) permeability, brain water content, and histological changes were assessed at scheduled time points. The animals subjected to TBI exhibited spatial cognitive decline in the Morris water maze (MWM) test, which was accompanied by inhibition of hippocampal long-term potentiation (LTP) induction at the perforant path-dentate gyrus (PP-DG) synapses. Additionally, TBI caused BBB disruption, brain edema, and neuronal loss. Interestingly, treatment with chrysin (especially in the dose of 100 mg/kg) alleviated all the above-mentioned neuropathological changes related to TBI. The results provide evidence that chrysin improves TBI-induced spatial cognitive decline, which may be partly related to the amelioration of hippocampal synaptic dysfunction, alleviation of BBB disruption, reduction of brain edema, and prevention of neuronal loss.

Effect of Gallic Acid Pretreatment and SGK1 Enzyme Inhibition on Cardiac Function and Inflammation in a Rat Model of Ischemia-Reperfusion Injury.

Background: Serum and glucocorticoid-induced kinase 1 (SGK1) is an enzyme that may play an important role in ischemic-reperfusion (I/R) injury and myocardial dysfunction. Although many studies have been conducted on individual antioxidants, little attention has been paid to the effects of co-administration of an antioxidant with an SGK1 inhibitor on cardiac function after I/R. Methods: This study aimed to determine the effects of gallic acid (as an antioxidant) combined with an SGK1 inhibitor on I/R-induced cardiac dysfunction and inflammation. Sixty male Wistar rats were randomized into 6 groups, pretreated with gallic acid or vehicle for 10 days. Subsequently, the heart was isolated and exposed to I/R. In groups that received the SGK1 inhibitor, the heart was perfused with the SGK1 inhibitor GSK650394, 5 min before induction of ischemia. After that, cardiac function, inflammatory factors, and myocardial damage were evaluated. Results: The combination of these two compounds improved cardiac contractility, heart rate, rate pressure product, left ventricular developed pressure, left ventricular systolic pressure, perfusion pressure, and QRS voltage significantly (P < 0.05). In addition, concomitant therapy of these two agents reduced tumor necrosis factor-alpha and interleukin-6, and the activity of creatine kinase-MB, lactate dehydrogenase, and troponin-I (P < 0.05). Conclusion: The results indicated that administration of gallic acid with the SGK1 inhibitor may have a potentiating effect on the improvement of cardiac dysfunction and I/R-induced inflammation.

Dose-dependent neuroprotective effects of adipose-derived mesenchymal stem cells on amyloid ß-induced Alzheimer's disease in rats.

AIM: Mesenchymal stem cells (MSCs) have emerged as an intriguing candidate in cell therapy for treating neurodegenerative diseases, including Alzheimer's disease (AD). To achieve the maximum efficiency of cell therapy, determining the optimal dose of MSCs is essential. This study was conducted to assess the dose-dependent therapeutic response of MSCs against pathological and behavioral AD-associated alterations. METHODS: Aß1-42 was injected intrahippocampally to establish an AD rat model. The MWM test was utilized to evaluate the animal's behavioral functions after receiving low and high doses of MSCs in the hippocampus region. ELISA and RT-qPCR were also employed to assess the concentration of markers related to antioxidant activity and inflammation and the gene expression related to apoptosis in the hippocampus region, respectively. RESULTS: Low-dose MSC transplantation by increasing the concentrations of the antioxidant GSH, the anti-inflammatory cytokine IL-10, as well as by lowering the concentrations of TNF-α, and the expression levels of apoptotic factors (Bax and caspase 3), exerted a neuroprotective effect in the hippocampus of AD rats and relatively ameliorated spatial learning and memory impairments. However, increasing the dose of MSCs decreased the therapeutic benefits of these cells and had no significant effect on the recovery of behavioral disorders. CONCLUSION: Our findings reveal the dose-dependent neuroprotective effect of MSCs in AD. The therapeutic response of MSCs to ameliorate the pathological and behavioral alterations associated with AD is attenuated when the dosage of MSCs is increased.

Sesamin alleviates defects in seizure, behavioral symptoms, and hippocampus electroencephalogram in a pentylenetetrazol rat model.

Objectives: Seizure is a prevalent disorder reflected by powerful and sudden activity of neural networks in the brain that leads to tonic-clonic attacks. These signs may be due to an increase in excitatory/inhibitory neurotransmitters ratio. So, the current experiment aimed to examine the seizure and neurobehavioral parameters, as well as the hippocampus local electroencephalogram (EEG) after seizure with and without sesamin pretreatment. Materials and Methods: Sesamin (15, 30, and 60 mg/kg/5 ml, intraperitoneal or IP, vehicle: dimethyl sulfoxide or DMSO, for 3 days) was administrated before pentylenetetrazol (PTZ) (60 mg/kg/10 ml, IP, vehicle: saline), which induces acute seizure in adult male Wistar rats (230 ± 20 g, six weeks old). Different phases of seizures (score, latency, duration, and frequency), behavioral parameters (passive avoidance memory, anxiety, and locomotor activity), and hippocampus local EEG were evaluated after the injections. At the end of the experiments, oxidative stress markers plus gene expression of phosphoinositide 3-kinase/protein kinase B or PI3K/Akt mRNA were measured in the hippocampus. Results: Pretreatment with sesamin (30 mg/kg) could significantly decrease seizure scores and oxidative stress in the hippocampus. PTZ injection induced EEG deficits and neurobehavioral impairments which were significantly decreased by sesamin, especially in Beta, Theta, and delta EEG waves. Also, the expression of PI3K/Akt significantly increased in the sesamin (30 mg/kg) group in comparison with the PTZ group. Conclusion: Sesamin could prevent seizure attacks and neurobehavioral and EEG deficits induced by pentylenetetrazol, probably through the PI3K/Akt signaling pathway.

The renoprotective effects of hesperidin on kidney injury induced by exposure to severe chronic dust storm particulate matter through inhibiting the Smads/TGF-ß1 signaling in rat.

Exposure to dust storm particulate matter (PM) is detrimental to kidney tissue. In this study, the impacts of chronic intake of dusty PM were explored as a major objective in a specified compartment to make a real-like dust storm (DS) model, and the role of hesperidin (HSP) as an antioxidant on kidney tissue was assessed in rats. Thirty-two male Wistar rats (200-220 g) were randomly allocated into 4 groups: CA+NS: (clean air and normal saline as a vehicle of HSP). Dusty PM and NS (DS+NS). HSP+ CA: rats received 200 mg/kg of HSP by gavage for 28 days, once daily in addition to exposure to clean air. HSP+DS: HSP plus DS. In DS groups, the animals were exposed to dust storms at a concentration of 5000-8000 µg/m3 in the chamber for 1 h daily, for 4 consecutive weeks, except Thursdays and Fridays. At the end of the experiment, the animals were sacrificed for biochemical, inflammatory, oxidative stress, molecular parameters, and histological evaluation. DS significantly enhanced blood urea nitrogen and creatinine, inflammatory (tumor necrosis factor-α, and interleukin-1ß), and oxidative stress indexes. Likewise, a significant increase was seen in mRNA Smads, collagen-I, and transforming growth factor-ß1 (TGF-ß1) expressions in the kidney. Histological findings showed contracted glomeruli and kidney structure disorder. In addition, Masson's trichrome staining demonstrated renal fibrosis. Nevertheless, HSP could significantly reverse these changes. Our data confirmed that DS results in kidney fibrosis through enhancing Smads/TGF-ß1 signaling. However, HSP was able to inhibit these changes as confirmed by histological findings.

Anandamide improves food intake and orexinergic neuronal activity in the chronic sleep deprivation induction model in rats by modulating the expression of the CB1 receptor in the lateral hypothalamus.

Sleep deprivation alters orexinergic neuronal activity in the lateral hypothalamus (LH), which is the main regulator of sleep-wake, arousal, appetite, and energy regulation processes. Cannabinoid receptor (CBR) expression in this area is involved in modulating the function of orexin neurons. In this study, we investigated the effects of endocannabinoid anandamide (AEA) administration on improving food intake and appetite by modulating the activity of orexin neurons and CB1R expression after chronic sleep deprivation. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation +20 mg/kg AEA (SD + A). For SD induction, the rats were kept in a sleep deprivation device for 18 h (7 a.m. to 1 a.m.) daily for 21 days. Weight gain, food intake, the electrical power of orexin neurons, CB1R mRNA expression in hypothalamus, CB1R protein expression in the LH, TNF-α, IL-6, IL-4 levels and antioxidant activity in hypothalamus were measured after SD induction. Our results showed that AEA administration significantly improved food intake (p < 0.01), Electrical activity of orexin neurons (p < 0.05), CB1R expression in the hypothalamus (p < 0.05), and IL-4 levels (p < 0.05). AEA also reduced mRNA expression of OX1R and OX2R (p < 0.01 and p < 0.05 respectively), also IL-6 and TNF-α (p < 0.01) and MDA level (p < 0.05) in hypothalamic tissue. As a consequence, AEA modulates orexinergic system function and improves food intake by regulating the expression of the CB1 receptor in the LH in sleep deprived rats.

Effect of Berberine against Cognitive Deficits in Rat Model of Thioacetamide-Induced Liver Cirrhosis and Hepatic Encephalopathy (Behavioral, Biochemical, Molecular and Histological Evaluations).

BACKGROUND: Liver cirrhosis (LC) is one of the chronic liver diseases with high disability and mortality accompanying hepatic encephalopathy (HE) followed by cognitive dysfunctions. In this work, the effect of berberine (Ber) on spatial cognition was studied in a rat model of LC induced by thioacetamide (TAA). MATERIALS AND METHODS: Male Wistar rats (200-250 g) were divided into six groups: (1) control; (2) TAA, 200 mg/kg/day, i.p.; (3-5) TAA + Ber; received Ber (10, 30, and 60 mg/kg, i.p., daily after last TAA injection); (6) Dizocilpine (MK-801) + TAA, received MK-801 (2 mg/kg/day, i.p.) 30 m before TAA injection. The spatial memory, BBB permeability, brain edema, liver enzymes, urea, serum and brain total bilirubin, oxidative stress and cytokine markers in the hippocampus were measured. Furthermore, a histological examination of the hippocampus was carried out. RESULTS: The BBB permeability, brain edema, liver enzymes, urea, total bilirubin levels in serum and hippocampal MDA and TNF-α increased significantly after TAA injection (p < 0.001); the spatial memory was impaired (p < 0.001), and hippocampal IL-10 decreased (p < 0.001). Ber reversed all the above parameters significantly (p < 0.05, p < 0.01 and p < 0.001). MK-801 prevented the development of LC via TAA (p < 0.001). CONCLUSION: Results showed that Ber improves spatial learning and memory in TAA-induced LC by improving the BBB function, oxidative stress and neuroinflammation. Ber might be a promising therapeutic agent for cognitive improvement in LC.

Preconditioning adipose-derived mesenchymal stem cells with dimethyl fumarate promotes their therapeutic efficacy in the brain tissues of rats with Alzheimer's disease.

AIM: Transplantation of mesenchymal stem cell (MSC) has been suggested to be a promising method for treating neurodegenerative conditions, including Alzheimer's disease (AD). However, the poor survival rate of transplanted MSCs has limited their therapeutic application. This study aimed to evaluate whether preconditioning MSCs with dimethyl fumarate (DMF), a Nrf2 inducer, could enhance MSC therapeutic efficacy in an amyloid-ß (Aß1-42)-induced AD rat model. METHODS: The survival and antioxidant capacity of MSCs treated with DMF were assessed in vitro. Aß1-42 intrahippocampal injection was used to create a rat model of AD. Following the transplantation of MSCs preconditioned with DMF and using the Morris blue maze test, spatial learning and memory were assessed. Using RT-qPCR, we evaluated the gene expression related to apoptosis and neurotrophins in the hippocampus region. RESULTS: Treatment with DMF enhanced cell survival and Nrf2 protein expression in MSCs in vitro. Preconditioning with DMF also enhanced the efficacy of transplanted MSCs in rescuing learning and spatial memory deficits in Aß-AD rats. Besides, DMF preconditioning enhanced the neuroprotective effect of transplanted MSCs in the hippocampus of rats treated with Aß1-42 by decreasing the expression of apoptotic markers (Bax, caspase 3, and cytochrome c), and elevating the expression of the anti-apoptotic marker Bcl2 and neurotrophins, including BDNF and NGF. CONCLUSION: Preconditioning MSCs with DMF boosted the therapeutic efficacy of these cells; therefore, it could serve as a targeted strategy for increasing the therapeutic efficacy of MSCs in treating neurodegenerative disorders, including AD.

Effects of Gallic Acid on Memory Deficits and Electrophysiological Impairments Induced by Cerebral Ischemia/Reperfusion in Rats Following Exposure to Ambient Dust Storm.

We aimed to investigate the probable protective effects of gallic acid (GA) on cognitive deficits, hippocampal long term potentiation (LTP) impairments, and molecular changes induced by cerebral ischemia/reperfusion (I/R) in rats following exposure to ambient dust storm. After pretreatment with GA (100 mg/kg), or vehicle (Veh) (normal saline, 2 ml/kg) for ten days, and 60 minutes' exposure to dust storm including PM (PM, 2000-8000 g/m3) every day, 4-vessel occlusion (4VO) type of I/R was induced. Three days after I/R induction, we evaluated behavioral, electrophysiological, histopathological, molecular and brain tissue inflammatory cytokine changes. Our findings indicated that pretreatment with GA significantly reduced cognitive impairments caused by I/R (P < 0.05) and hippocampal LTP impairments caused by I/R after PM exposure (P < 0.001). Additionally, after exposure to PM, I/R significantly elevated the tumor necrosis factor α content (P < 0.01) and miR-124 level (P < 0.001) while pre-treatment with GA reduced the level of miR-124 (P < 0.001). Histopathological results also revealed that I/R and PM caused cell death in the hippocampus CA1 area (P < 0.001) and that GA decreased the rate of cell death (P < 0.001). Our findings show that GA can prevent brain inflammation, and thus cognitive and LTP deficits caused by I/R, PM exposure, or both.

Anti-inflammatory, anti-apoptotic, and neuroprotective potentials of anethole in Parkinson's disease-like motor and non-motor symptoms induced by rotenone in rats.

Parkinson's disease (PD) is a complex neurological disorder characterized by a combination of motor and non-motor symptoms (NMS). Antioxidant and anti-inflammatory compounds are considered a potential therapeutic strategy against PD. The present study examined the neuroprotective effects of anethole as a potent antioxidant and anti-inflammatory agent against motor and non-motor deficits induced by rotenone toxicity. Rats were treated with anethole (62.5, 125, and 250 mg/kg, i.g) concomitantly with rotenone (2 mg/kg, s.c) for 5 weeks. After the treatment, behavioral tests were performed to evaluate motor function and depression-/anxiety-like behaviors. After the behavioral tests, rats were decapitated and brains were removed for histological analysis. Striatum samples were also isolated for neurochemical, and molecular analysis. Our data showed that rotenone-induced motor deficit, anxiety-and depression-like behaviors were significantly improved in rats treated with anethole. Furthermore, anethole treatment reduced inflammatory cytokines tumor necrosis factor α (TNFα) and Interleukin 6 (IL-6), and increased anti-inflammatory cytokine IL-4 in the striatum of rotenone-induced PD rats. Western blot analysis showed that treatment with anethole markedly suppressed caspase-3 activation induced by rotenone. Moreover, histological examination of striatum showed an increase in the number of surviving neurons after treatment with anethole. Anethole also significantly enhanced the striatal levels of dopamine in rotenone-induced PD rats. In addition, treatment with L-Dopa as a positive control group had effects similar to those of anethole on histological, neurochemical, and molecular parameters in rotenone-induced parkinsonian rats. Our results suggested the neuroprotective effects of anethole through anti-inflammatory, anti-apoptotic, and antioxidant mechanisms against rotenone-induced toxicity in rats.