Hypolipidemic and hepatoprotective effects of corn silk extract in nicotine-administered male mice.

Aim: This study is done to investigate the hypolipidemic and hepatoprotective effects of corn silk extract in nicotine-administered male mice. Background: Nicotine can induce pathophysiological effects in the liver tissue through oxidative stress and damage cells. Corn silk can improve liver function with its antioxidant effects. Methods: In this experimental study, 30 male NMRI mice (25-30 gr) were divided into 5 groups: controls, sham, nicotine 2.5 mg/kg, nicotine+aqueous extract of corn silk 400 mg/kg, and nicotine+methanolic extract of corn silk 400 mg/kg for 1 month. One day after the last nicotine and extracts consumption, the serum samples were performed for biochemical measurement, and the supernatant of the homogenized liver was administered for antioxidant variables assessment. Results: There was no significant difference in the body weight of different groups. Liver weight and GSH decreased in the nicotine group compared to the control group (P<0.05). Triglycerides, total cholesterol, HDL-C, LDL-C, liver enzymes, and MDA increased in the nicotine group compared to the control group (P<0.05). Also, the expansion of sinusoids, the presence of inflammatory cells, and necrosis of liver cells were observed in the nicotine group compared to the control group. Using aqueous and methanolic extracts of corn silk in mice receiving nicotine led to the improvement of the mentioned variables (P<0.05). Conclusion: The results of this study showed that the use of nicotine can lead to the induction of hepatotoxicity. The use of aqueous and methanolic extracts of corn silk improved them through its antioxidant activity.

Neuroprotective effects of Royal Jelly (RJ) against pentylenetetrazole (PTZ)-induced seizures in rats by targeting inflammation and oxidative stress.

Epilepsy is a chronic neurological condition in which inflammation and oxidative stress play a key role in the pathogenesis. Recently, several studies have suggested that Royal Jelly (RJ) has antioxidant effects. Nevertheless, there is no evidence of its effectiveness against epilepsy. Here, we evaluated its neuroprotective effects at different doses (100 and 200 mg/kg) against pentylenetetrazole (PTZ)-induced seizures. Fifty male Wistar rats were randomly divided into five groups: control, PTZ, RJ100 + PTZ, RJ200 + PTZ and RJ100. In order to establish epilepsy model, 45 mg/kg of PTZ was injected intraperitoneally for 10 consecutive days. Seizure parameters were graded based on Racine's 7-point classification. Elevated-plus maze, Y maze and shuttle box tests were carried out to assess anxiety-like behavior, short-term memory, and passive avoidance memory, respectively. We used ELISA technique to measure the expression of the pro-inflammatory cytokines and oxidative stress factors. Also, neuronal loss in the hippocampal CA3 region was determined using Nissl staining. Our findings showed that PTZ-treated rats had more seizure intensity, anxiety-like behavior, memory dysfunction, higher levels of TNF-α, IL-1ß, and oxidative markers. RJ could allay seizure severity and duration. It also improved memory function as well as anxiety level. In terms of biochemical assessment, RJ gave rise to a significant decrease in the level of IL-1ß, TNF-α and MDA and it restored the activities of GPX and SOD enzymes. Hence, our study shows that RJ contains anti-inflammatory and antioxidative effects which contribute to less neuronal damage in the PTZ-induced epilepsy model.

Neuroprotective Effects of Conditioned Medium of Mesenchymal Stem Cells (MSC-CM) as a Therapy for Ischemic Stroke Recovery: A Systematic Review.

It has been reported that the therapeutic potential of stem cells is mainly mediated by their paracrine factors. In order to identify the effects of conditioned medium of mesenchymal stem cells (MSC-CM) against stroke, a systematic review was conducted. We searched PubMed, Scopus, and ISI Web of Science databases for all available articles relevant to the effects of MSC-CM against the middle cerebral artery occlusion (MCAO) model of ischemic stroke until August 2022. The quality of the included studies was evaluated using The STAIR scale. During the systematic search, a total of 356 published articles were found. A total of 15 datasets were included following screening for eligibility. The type of cerebral ischemia was the MCAO model and CM was obtained from MSCs. The results showed that the therapeutic time window can be considered a crucial factor when researchers use MSC-CM for stroke therapy. In addition, MSC-CM therapy contributes to functional recovery and reduces infarct volume after stroke by targeting different cellular signaling pathways. Our findings showed that MSC-CM therapy has the ability to improve functional recovery and attenuate brain infarct volume after ischemic stroke in preclinical studies. We hope our study accelerates needed progress towards clinical trials.

Effects of aqueous and hydro-alcoholic extracts of Seidlitzia rosmarinus on male mouse reproductive system: An experimental study.

OBJECTIVE: This study investigated the effects of aqueous and hydro-alcoholic extracts of Seidlitzia rosmarinus on reproductive hormones, sperm variables, and antioxidant enzymes level in the mice testis. METHODS: In this experimental study, 24 three-month-old male NMRI mice weighing (25-30g) were divided into three groups: control, aqueous and hydro-alcoholic extracts of Seidlitzia rosmarinus 100mg/kg. Dissolved extracts were gavaged orally for 35 days. One day after receiving the last dose of the extract, the blood sample, testis, and the epididymis tail were taken for plasma hormonal, testicular antioxidants level, sperm count, and vitality assessments. RESULTS: Testicular level of malondialdehyde increased in aqueous and hydro-alcoholic extracts groups (p=0.04); total antioxidant capacity decreased in aqueous and hydro-alcoholic extracts groups (p=0.008); and the consumption of aqueous (p<0.001) and hydro-alcoholic (p=0.03) extracts decreased catalase in comparison with the control group. The plasma level of luteinizing hormone decreased in the aqueous extracts administrated group (p=0.009); the follicle-stimulating hormone increased in aqueous (p=0.03), and hydro-alcoholic extracts administered mice; and the testosterone level decreased in aqueous extract-treated animals versus the control group (p<0.001). The sperm count was increased in aqueous (p=0.04) and hydro-alcoholic (p=0.009) extracts groups, but its vitality was decreased (p=0.008) in comparison with the control group. CONCLUSIONS: In conclusion, Seidlitzia rosmarinus has an adverse effect on male reproductive hormones and sperm viability via increased lipid peroxidation and reduced antioxidant defense system performance.

TLR4 /NF-ĸB and JAK2/STAT3 signaling pathways: Cellular signaling pathways targeted by cell-conditioned medium therapy in protection against ischemic stroke.

Human amniotic membrane-derived mesenchymal stem cell-conditioned medium (hAMSC-CM) has been known to improve neuronal survival following ischemic stroke. The present study was designed to examine whether protective effects of hAMSC-CM against stroke can be linked to reducing neuroinflamation by targeting TLR4 /NF-ĸB and Jak2/Stat3 signaling pathways. Immunohistochemistry of hippocampus and western blot assay were performed to evaluate the expression of TLR4 /NF-ĸB and Jak2/Stat3, respectively. Real-time PCR assay was applied to investigate the mRNA levels of Jak2/Stat3. Hematoxylin and eosin (H&E) staining was used to investigate tissue damage and morphological changes in the CA1 region of hippocampus. Increased brain edema was seen in middle cerebral artery occlusion (MCAO) rats compared to sham. Post-treatment with hAMSC-CM markedly reduced brain edema in comparison with MCAO group (P < 0.05). Compared to sham, significantly increased levels of TLR4 /NF-ĸB and Jak2/Stat3 were seen in MCAO rats. Intravenous injection of hAMSC-CM after reperfusion markedly reduced levels of TLR4 /NF-ĸB and Jak2/Stat3 in hippocampus region (P < 0.05). Tissue damage and neuronal cell increased in the CA1 region of hippocampus that reversed by post-treatment by hAMSC-CM. Interestingly, our finding showed that hAMSC-CM can be considered as good candidate to reduce injury following ischemic stroke by decreasing activity of TLR4 /NF-ĸB and Jak2/Stat3 signaling pathways.

FoxO1 and Wnt/ß-catenin signaling pathway: Molecular targets of human amniotic mesenchymal stem cells-derived conditioned medium (hAMSC-CM) in protection against cerebral ischemia/reperfusion injury.

Ischemia-reperfusion (I/R) injury has weakened the effects of available treatment options for ischemic stroke. Although conditioned medium obtained from human amniotic mesenchymal stem cells (hAMSC-CM) has been reported to exert protective effect against stroke, detailed knowledge about its possible molecular mechanisms is not still completely available. The present study was designed to investigate whether hAMSC-CM can modulate FoxO1 and Wnt/ß-catenin signaling pathway after ischemic stroke to create neuroprotective effects. Middle cerebral artery occlusion (MCAO) model with male Wistar rats was used to evaluate the effects of hAMSC-CM on activities of FoxO1, Wnt/ß-catenin signaling pathway, and endogenous antioxidant system and apoptotic cell death. The results demonstrated that induction of MCAO significantly reduced activities of FoxO1, Wnt/ß-catenin signaling pathway, and endogenous antioxidant system and enhanced apoptotic cell death (P < 0.05). In addition, treatment by hAMSC-CM immediately after cerebral reperfusion resulted in significantly reduced infarct size and increased activities of FoxO1, Wnt/ß-catenin signaling pathway, and restoring endogenous antioxidant system and suppressing apoptotic cell death (P < 0.05). Likewise, increased activity of Wnt/ß-catenin signaling pathway resulted in suppressing the neuroinflammation by inhibiting the expression of TNF-α and increasing the expression of IL-10. These findings demonstrate that hAMSC-CM can be considered as an excellent candidate in the treatment of acute ischemic stroke in clinical routine.

Pharmacological evidence for the involvement of the opioid system in the antidepressant-like effect of simvastatin in mice: Without tolerance and withdrawal syndrome.

Statins, 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors, have been shown to be effective in reducing depression in animal models. The present study aimed to investigate the potential antidepressant-like activity of simvastatin and the possible involvement of opioid systems in the mouse forced swimming test (FST). After assessment of locomotor behavior in the open-field test (OFT), FST was applied for evaluation of depressive behavior in mice. Simvastatin (20, 30, and 40 mg/kg, i.p.) or morphine (0.01, 0.1, 1 and 10 mg/kg, i.p.) were administrated 30 min before the OFT or FST. Results showed that simvastatin produced antidepressant effect in a dose-dependent manner. The effect of simvastatin (30 mg/kg) was prevented by the pre-treatment of mice with naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist). In addition, a sub-effective dose of simvastatin (20 mg/kg) produced a synergistic antidepressant-like effect in the FST with a sub-effective dose of morphine (0.1 mg/kg) that it was reversed by naloxone. Moreover, in contrast to morphine, treatment with simvastatin for six days induced neither tolerance to the antidepressant-like effect nor withdrawal signs. In conclusion, these findings demonstrated that simvastatin elicited antidepressant-like action possibly through the stimulation of opioidergic pathways, without inducing tolerance and withdrawal signs.

Simvastatin exerts antidepressant-like activity in mouse forced swimming test: Role of NO-cGMP-KATP channels pathway and PPAR-gamma receptors.

Simvastatin, one of the lipophilic statins, has been shown to be effective in reducing depression in rodents. The present study aimed to investigate the potential antidepressant-like activity of simvastatin and the possible involvement of NO-cGMP-KATP channels pathway and PPARγ using forced swimming test (FST) in mice. In addition, the interaction between simvastatin and fluoxetine as a reference drug was examined. After assessment of locomotor behavior in the open-field test (OFT), FST was applied for evaluation of depressive behavior in mice. Simvastatin at doses (20, 30, and 40 mg/kg, i.p.) was administrated 30 min before the OFT or FST. To evaluate the involvement of NO-cGMP-KATP channels pathway, mice were pre-treated intraperitoneally with l-arginine (a nitric oxide precursor, 750 mg/kg), L-NAME (a NOS inhibitor, 10 mg/kg), methylene blue (guanylyl cyclase inhibitor, 20 mg/kg), sildenafil (a PDE-5 inhibitor, 5 mg/kg), glibenclamide (ATP-sensitive K+ channel blocker, 1 mg/kg), and diazoxide (K+ channels opener, 10 mg/kg). Moreover, to clarify the probable involvement of PPARγ receptors, pioglitazone, a PPARγ agonist (5 mg/kg, i.p.), and GW9662, a PPARγ antagonist (2 mg/kg, i.p.), were pre-treated with simvastatin. Immobility time was significantly decreased after simvastatin injection. Administration of L-NAME, methylene blue, glibenclamide and pioglitazone in combination with the sub-effective dose of simvastatin (20 mg/kg, i.p.) reduced the immobility time in the FST compared to drugs alone, while co-administration of effective doses of simvastatin (30 mg/kg, i.p.) with l-arginine, sildenafil, diazoxide, and GW9662 prevented the antidepressant-like effect of simvastatin. In addition, simvastatin (20 mg/kg) potentiated the antidepressant-like effect of fluoxetine through the NO pathway. None of the drugs produced any significant alterations in locomotor activity using OFT. These results demonstrated that NO-cGMP-KATP channels pathway and PPARγ receptors may be involved in the antidepressant-like effect of simvastatin.

Protective effects of gallic acid against methotrexate-induced toxicity in rats.

BACKGROUND: Methotrexate, as a chemotherapy drug, can cause chronic liver damage and oxidative stress. Aim of this study was to evaluate the preventive effect of gallic acid (GA) on methotrexate (MTX)-induced oxidative stress in rat liver. METHODS: Twenty-eight male rats were randomly divided into four groups as control, MTX (20 mg/kg, i.p.), MTX + GA (30 mg/kg/day, orally) and GA treated. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury. Malondialdehyde (MDA) and glutathione (GSH) levels and hepatic antioxidant enzymes activities including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were assayed in liver tissue. The expression of SOD2 and GPx1 genes were evaluated by real-time RT-PCR and liver histopathology was evaluated by light microscopy. RESULTS: The result obtained from current study showed that GA remarkably reduced MTX-induced elevation of AST, ALT and ALP and increased MTX-induced reduction in GSH content, GPx, CAT and SOD activity as well as GPx1 and SOD2 gene expressions. Histological results showed that MTX led to liver damage and GA could improve histological changes. CONCLUSIONS: Our results indicate that GA ameliorates biochemical and oxidative stress parameters in the liver of rats exposed to MTX.

Measuring engagement in nurses: the psychometric properties of the Persian version of Utrecht Work Engagement Scale.

Background: Considering the overall tendency in psychology, researchers in the field of work and organizational psychology have become progressively interested in employees' effective and optimistic experiments at work such as work engagement. This study was conducted to investigate 2 main purposes: assessing the psychometric properties of the Utrecht Work Engagement Scale, and finding any association between work engagement and burnout in nurses. Methods: The present methodological study was conducted in 2015 and included 248 females and 34 males with 6 months to 30 years of job experience. After the translation process, face and content validity were calculated by qualitative and quantitative methods. Moreover, content validation ratio, scale-level content validity index and item-level content validity index were measured for this scale. Construct validity was determined by factor analysis. Moreover, internal consistency and stability reliability were assessed. Factor analysis, test-retest, Cronbach's alpha, and association analysis were used as statistical methods. Results: Face and content validity were acceptable. Exploratory factor analysis suggested a new 3- factor model. In this new model, some items from the construct model of the original version were dislocated with the same 17 items. The new model was confirmed by divergent Copenhagen Burnout Inventory as the Persian version of UWES. Internal consistency reliability for the total scale and the subscales was 0.76 to 0.89. Results from Pearson correlation test indicated a high degree of test-retest reliability (r = 0. 89). ICC was also 0.91. Engagement was negatively related to burnout and overtime per month, whereas it was positively related with age and job experiment. Conclusion: The Persian 3- factor model of Utrecht Work Engagement Scale is a valid and reliable instrument to measure work engagement in Iranian nurses as well as in other medical professionals.

Neuroprotective Effects of Ellagic Acid in a Rat Model of Parkinson's Disease.

Antioxidants have protective effects against free radicals-induced neural damage in Parkinson's disease (PD). We examined the effects of ellagic acid (EA) on locomotion, pallidal local EEG, and its frequency bands' power and also cerebral antioxidant contents in a rat model of PD induced by 6-hydroxidopamine (6-OHDA). 6-OHDA (16 µg/2µ l) was injected into the right medial forebrain bundle (MFB) in MFB-lesioned rat's brain. Sham group received vehicle instead of 6-OHDA. PD-model was confirmed by rotational test using apomorphine injection. EA (50 mg/kg/2 ml, by gavages) was administered in PD+EA group. One group of MFB-lesioned rats received pramipexole (PPX; 2 mg/kg/2 ml, by gavages) as a positive control group (PD+PPX group). Motor activity was assessed by stride length, rotarod, and cylinder tests. Pallidal local EEG was recorded in freely moving rats. The levels of malondialdehyde (MDA) besides Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured in both striatum and hippocampus tissues. MFB lesion caused significant reduction of stride-length (P<0.001), bar decent latency (P<0.001) and frequency bands' power of pallidal EEG (P<0.001). Use of 6-OHDA caused a reduction in the GPx (P<0.001) and SOD (P<0.001) activities while increased significantly the levels of MDA (P<0.001) in MFB-lesioned rats. EA significantly restored all above parameters. The results show that EA can improve the motor impairments and electrophysiological performance in the MFB-lesioned rats via raising the cerebral antioxidant contents. Therefore, EA can protect the brain against free radicals-induced neural damage and may be beneficial in the treatment of PD.

Ellagic acid improves hyperalgesia and cognitive deficiency in 6-hydroxidopamine induced rat model of Parkinson's disease.

OBJECTIVES: Parkinson's disease (PD) is known for motor impairments. But often, there are non-motor symptoms such as cognitive deficiency and pain misperception, owing to possible role of nigrostriatal pathway. Antioxidants have protective effect on free radical-induced neuronal damage in PD. To further address, we examined the effects of ellagic acid (EA) in a rat model of PD induced by 6-hydroxidopamine (6-OHDA). MATERIALS AND METHODS: Right medial forebrain bundle (MFB) was lesioned by injecting 6-OHDA (16 µg/2 µl), in PD-animals. Sham operated animals received vehicle instead of 6-OHDA. PD was approved by apomorphine-induced contralateral rotation. EA (50 mg/kg/2 ml, PO, for 10 days) was administered to PD-EA group. Some PD-animals received pramipexole (PPX; 2 mg/kg/2 ml, PO) as a positive control group. Analgesia was measured by tail-flick and hot-plate tests. Passive avoidance task was measured by shuttle box apparatus to record the initial and step-through latency. Spatial cognition task was evaluated by Morris water maze test, measuring the escape latency time, path length, swimming speed and time spent in target quadrant. RESULTS: MFB-lesioned rats showed hyperalgesic responses to the stimulus in tail-flick and hot-plate tests. Also they showed memory and learning deficit in cognitive tests. These effects reversed by EA treatment. CONCLUSION: 6-OHDA can induce oxidative stress and can disrupt the neural mechanisms underlying proper integration of painful stimuli and cognitive processes in MFB-lesioned rats. Consequently, nigrostriatal pathway can play possible role in nociception and cognition. EA, a natural antioxidant, has neuroprotective effect on this pathway and can ameliorate this defect and be considered in PD management.

Ellagic Acid Protects the Brain Against 6-Hydroxydopamine Induced Neuroinflammation in a Rat Model of Parkinson's Disease.

INTRODUCTION: Neuroinflammation may play as an important risk factor in progressive degeneration of dopaminergic cells. Antioxidants have protective effects against free radicals-induced neural damage in Parkinson's disease (PD). In the present study, we examined the effects of ellagic acid (EA) on locomotion and neuroinflammatory biomarkers in a rat model of PD induced by 6-hydroxidopamine (6-OHDA). METHODS: 6-OHDA (16 µg/2 µl) was injected into the right medial forebrain bundle (MFB) in MFB-lesioned rat's brain. Sham group received vehicle instead of 6-OHDA. PD-model was confirmed by rotational test using apomorphine injection. EA (50 mg/kg/2 ml, by gavages) was administered in PD+EA group. One group of MFB-lesioned rats received pramipexole (PPX; 2 mg/kg/2 ml, by gavages) as positive control group (PD+PPX group). Motor activity was assessed by stride length and cylinder tests. The levels of TNF-α and IL-1ß were measured in both striatum and hippocampus tissues. RESULTS: MFB lesion caused significant reduction of stride-length (P<0.001) and also increased the contralateral rotations (P<0.001) and score of the cylinder test (P<0.001). Use of 6-OHDA to induce the PD significantly increased the levels of TNF-α (P<0.001) and IL-1ß (P<0.001) in MFB-lesioned rats. EA significantly restored all of the above parameters. DISCUSSION: EA can improve the motor impairments in the MFB-lesioned rats via reducing the neuroinflammatory biomarkers and protect the brain against free radicals-induced neural damage. The results suggest that EA can be helpful in management of PD treatment.