A preliminary study of the anti-inflammatory and anti-apoptotic effects of crocin against gastric ischemia-reperfusion injury in rats

O objetivo do presente estudo foi investigar o efeito protetor da crocina em lesões da mucosa gástrica causadas por isquemia-reperfusão (I/R) em ratos. Trinta e dois ratos machos aleatoriamente divididos em grupos de ratos normais, operados como controle, I/R. I/R + pré-tratamento com crocina e crocina sozinha. Para induzir lesões I/R, a artéria celíaca foi grampeada durante 30 minutos e, em seguida, o grampo foi removido para permitir a reperfusão por 3 h. Ratos com pré-tratamento com crocina receberam crocina (15 mg/kg, ip) 30 minutos antes da indução do dano I/R. Amostras de mucosa gástrica foram coletadas para qiuantificar a expressão da proteína da caspase-3, o fator apoptótico, e óxido nítrico sintase induzível (iNOS), uma proteína anti-inflamatória, pela técnica de Western Blot. O pré-tratamento com crocina diminuiu a área total de lesões gástricas e a expressão de níveis de caspase-3 e iNOS induzidas pelo dano I/R. Nossos resultados mostraram o efeito protetor da crocina na mucosa gástrica contra o dano I/R. Este efeito foi mediado, principalmente, por diminuição da expressão das proteínas iNOS e caspase-3.The aim of the present study was to investigate the protective effect of crocin on gastric mucosal lesions caused by ischemia-reperfusion (I/R) injury in rats. Thirty-two male rats were randomly divided into sham, I/R, I/R + crocin pretreatment and crocin alone groups. To induce I/R lesions, the celiac artery was clamped for 30 min, and the clamp was then removed to allow reperfusion for 3 h. Crocin-pretreated rats received crocin (15 mg/kg, i.p.) 30 min prior to the induction of I/R injury. Samples of gastric mucosa were collected to quantify the protein expression of caspase-3, an apoptotic factor, and inducible nitric oxide synthase (iNOS), a pro-inflammatory protein, by Western blot. Pretreatment with crocin decreased the total area of gastric lesions and decreased the protein expression levels of caspase-3 and iNOS induced by I/R injury. Our findings showed a protective effect of crocin in gastric mucosa against I/R injury. This effect of crocin was mainly mediated by reducing the protein expression of iNOS and caspase-3

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

Objective(s): 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

Adipose Tissue-Derived Mesenchymal Stem Cells Alter Metabolites of Brain Cholesterol Homeostasis in An Alzheimer’s Model

Objective: Disruption of cholesterol homeostasis in Alzheimer’s disease (AD) plays a crucial role in diseasepathogenesis, making it a potential therapeutic target. Mesenchymal stem cells (MSCs) show promise in treatingcognitive impairment and provide a novel therapeutic approach. This study aims to investigate the effects of MSCs onspecific metabolites associated with brain cholesterol homeostasis in an AD rat model.Materials and Methods: In this experimental study, animals were divided into three groups: control, AD, andAD+MSCs. AD was induced using amyloid beta (Aβ) and confirmed through the Morris water maze (MWM) behaviouraltest and Congo red staining. MSCs were extracted, characterised via flow cytometry, subjected to osteoblast andadipose differentiation, and injected intraventricularly. The cholesterol metabolite levels were measured using gaschromatography-mass spectrometry (GC)-MS and compared among the groups.Results: Treatment with MSCs significantly improved memory function in the AD+MSCs group compared to theAD group and the number of beta-amyloid plaques decreased according to histological assessment. Disturbancesin the brain cholesterol metabolites that included desmosterol, 7-dehydrocholesterol, 24S-hydroxycholesterol,27-hydroxycholesterol and cholesterol were observed in the AD group compared to the control group. Treatment withMSCs resulted in significant alterations in the levels of these metabolites.Conclusion: The findings indicate that MSC therapy has the potential to improve AD by modulating brain cholesterolhomeostasis and promoting the differentiation of stem cells into nerve cells. The results emphasize the importance ofinvestigating the role of cholesterol metabolites in the context of MSC therapy to gain deeper insights into underlyingmechanisms of the therapeutic efficacy of MSCs in AD

Effects of Vitex agnus-castus fruit on sex hormones and antioxidant indices in a d-galactose-induced aging female mouse model

Background: Aging is associated with the loss of endocrine function. In this study, Vitex agnus-castus (Vitex), which has antioxidant effects and high levels of phytoestrogen, was investigated with regard to the hypothalamic-pituitary-gonadal axis and antioxidant indices in natural aging and in a d-galactose induced aging model in female mice. Methods: The mice were subcutaneously injected with d-galactose (500 mg/kg/d for 45 days). Extract of Vitex (600 mg/kg/bid for 7 days by gavage) was used to treat d-galactose-induced aging and natural aging in mice. Seventy-two female NMRI mice (48 3-month-old normal mice and 24 18-24-month-old mice), weighing 30–35 g were randomly divided into six groups: control, Vitex, d-galactose, Vitex + d-galactose, Aging, and Vitex + Aging. The antioxidant indices and sex hormone levels were subsequently measured by enzyme-linked immunosorbent assay kits. Results: Body weight and the levels of malondialdehyde (MDA), follicle-stimulating hormone, and luteinizing hormone levels were significantly increased in the d-galactose aging and natural aging groups, whereas catalase and superoxide dismutase (SOD) activity and estrogen level were significantly decreased in these same groups. d-Galactose can also disrupt the estrous cycle and damage the uterus and ovarian tissues. Vitex could effectively attenuate these alterations. Conclusion: Vitex improved some aging events in the reproductive system of female mice. Therefore, because of its apparent antiaging effects, Vitex can be suitable for some aging problems such as oxidative stress, female sex hormone deficiency, and an atrophic endometrium

Effect of One Session of Resistance Exercises on Expression of BDNF Gene and TrkB Receptor in Alzheimer Model Male Wistar Rats

Background & Objective: This study is intended to evaluate the effect of One Session of resistance exercises on expression of BDNF gene and TrkB receptor in Alzheimer model male Wistar rats.  Materials & Methods: 32 mature male Wistar rats with mean weight of 230 to 280 grams were chosen and divided into Alzheimer and Sham groups. Rats in Sham group received normal saline while rats in Alzheimer group received STZ via intraventricular injection. These rats were then divided into the following four subgroups: 1. Resting Sham, 2. Exercising Sham, 3. Resting Alzheimer, and 4. Exercising Alzheimer. The two exercising rat subgroups, exercised 3 times a week for a period of 8 weeks. Exercise included lifting weight from the ladder. At the end of 8th week and 24 hours after last exercise session, the rats scarified by head separation. Hippocampus tissue was precisely extracted and samples were sent to laboratory for molecular and cellular tests. To determine the gene expression, RT-PCR method was used for analyzing the data and ANOVA was used. Results: The amount of BDNF, and TrkB between exercising rats and resting rats. These amounts were much higher in exercising Alzheimer rats group. Conclusion: It seems that eight weeks of resistance exercises increased expression of BDNF gene and TrkA an TrkB receptor in Alzheimer model Wistar rats

Pomegranate seed hydroalcoholic extract improves memory deficits in ovariectomized rats with permanent cerebral hypoperfusion /ischemia

Objective: Estrogen deficit following menopause results in cognitive behaviors impairment. Severity of these impairments in menopause women suffer with cerebral hypo perfusion/ischemia (HI) cause the brain damage and neuronal death. This study aimed to evaluate the effects of pomegranate seed extract (PGSE) on avoidance memories after permanent bilateral common carotid arteries occlusion (2CCAO) in ovariectomized (OVX) rats. Materials and Methods: Adult female Wistar rats were divided randomly into eight groups with 8 rats in each group: 1) Sham-operated for ovaries and 2CCAO (ShO); 2) OVX and sham operated for ischemia (OShI); 3-7) OVX with 2CCAO (OI) received PGSE (100, 200, 400 and 800 mg/2ml/kg or normal saline, orally) for 14 days (OI+E100, 200, 400, 800 or OI+Veh); 8) OShI received most effective dose of PGSE (200 and 400 mg/kg for passive and active avoidance memories respectively). Active and passive avoidance tasks were measured in Y-maze and two-way shuttle box respectively. Data were analyzed with one-way and RM-ANOVA followed by HSD post-hoc test. Results: Sensorimotor impaired in OShI+Veh and OI+Veh (

A preliminary study of the anti-inflammatory and anti-apoptotic effects of crocin against gastric ischemia-reperfusion injury in rats

The aim of the present study was to investigate the protective effect of crocin on gastric mucosal lesions caused by ischemia-reperfusion (I/R) injury in rats. Thirty-two male rats were randomly divided into sham, I/R, I/R + crocin pretreatment and crocin alone groups. To induce I/R lesions, the celiac artery was clamped for 30 min, and the clamp was then removed to allow reperfusion for 3 h. Crocin-pretreated rats received crocin (15 mg/kg, i.p.) 30 min prior to the induction of I/R injury. Samples of gastric mucosa were collected to quantify the protein expression of caspase-3, an apoptotic factor, and inducible nitric oxide synthase (iNOS), a pro-inflammatory protein, by Western blot. Pretreatment with crocin decreased the total area of gastric lesions and decreased the protein expression levels of caspase-3 and iNOS induced by I/R injury. Our findings showed a protective effect of crocin in gastric mucosa against I/R injury. This effect of crocin was mainly mediated by reducing the protein expression of iNOS and caspase-3

The effects of gallic acid on pain and memory following transient global ischemia/reperfusion in Wistar rats

Objective: It is generally agreed that most of the phenomena observed during brain ischemia and reperfusion can be explained by the damage to membrane structure. Oxidative stress is resulted in an imbalance between high consumption of oxygen and low levels of endogenous antioxidants. It is known that gallic acid (GA) is a strong antioxidant. The present study was carried out to evaluate the effect of GA on ischemia/reperfusion (I/R)-induced brain injury in rats.  Materials and Methods: Wistar adult male rats weighing 200–250 g were divided into six groups as sham operated (Sh), ischemia/reperfusion (I/R) received normal saline (I+Veh), I/R groups treated with gallic acid (I+GA, 50, 100, or 200 mg/kg, orally, respectively), or with 100 mg /kg phenytoin (I+Phen). The global cerebral I/R injury was induced by occluding bilateral common carotid arteries (BCCA) for 20 min, followed by 5 days reperfusion in adult male rats. Results: It was found that administration of 100 mg/kg GA for 5 days before and 5 days after I/R induction reversed gait performance, sensorimotor disorders (

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

Objective(s):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