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.

Therapeutic effects of chrysin in a rat model of traumatic brain injury: A behavioral, biochemical, and histological study.

AIMS: Oxidative stress and apoptosis have major roles in the progression of traumatic brain injury (TBI)-associated motor and cognitive deficits. The present study was aimed to elucidate the putative effects of chrysin, a natural flavonoid compound, against TBI-induced motor and cognitive dysfunctions and possible involved mechanisms. MAIN METHODS: Chrysin (25, 50 or 100 mg/kg) was orally administered to rats starting immediately following TBI induction by Marmarou's weight-drop technique and continuously for 3 or 14 days. Neurological functions, motor coordination, learning and memory performances, histological changes, cell apoptosis, expression of pro- and anti-apoptotic proteins, and oxidative status were assayed at scheduled time points after experimental TBI. KEY FINDINGS: The results indicated that treatment with chrysin improved learning and memory disabilities in passive avoidance task, and ameliorated motor coordination impairment in rotarod test after TBI. These beneficial effects were accompanied by increased the concentrations of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), decreased malondialdehyde (MDA) content, prevented neuronal loss, diminished apoptotic index, elevated the expression of anti-apoptotic Bcl-2 protein, and reduced the expression of pro-apoptotic Bax protein in the cerebral cortex and hippocampus tissues. SIGNIFICANCE: Our findings suggest that both anti-oxidative and anti-apoptotic properties of chrysin (especially in the dose of 100 mg/kg) are possible mechanisms that improve cognitive/motor deficits and prevent neuronal cell death after TBI.

Ellagic acid improves electrocardiogram waves and blood pressure against global cerebral ischemia rat experimental models.

BACKGROUND: Global cerebral ischemia (GCIR) arises in patients that are shown a variety of clinical difficulty including cardiac arrest, asphyxia, and shock. In spite of advances in understanding of the brain, ischemia and protective effects to improve ischemic injury still remain unknown. The aim of our study was to investigate the effect of ellagic acid (EA) pretreatment in the rat models of global cerebral ischemia reperfusion. METHODS: This experimental study was conducted in 2014 at the Physiology Research Center of the Ahvaz Jundishapur University of Medical Sciences in Ahvaz, Iran. Adult male Wistar rats (250-300 g) were used in this study. GCIR was induced by bilateral vertebral and common carotid arteries occlusion (4-VO). 32 rats were divided randomly to four groups: 1) So (Sham) received normal saline as vehicle of EA, 2) EA, 3) normal saline + GCIR, and 4) EA + GCIR. After anesthesia (a mix of xylazine and ketamine), animal subjected to 20 minutes of ischemia followed by 30 minutes of reperfusion in related groups. EA (100 mg/kg, dissolved in normal saline) or 1.5 ml/kg normal saline was administered (gavage, 10 days) to the related groups. EEG was recorded from NTS in GCIR treated groups. RESULTS: Present data showed that: 1) EEG in GCIR treated groups was flattened; 2) Blood pressure, voltage of QRS and P-R interval were reduced significantly in the ischemic groups compared to before ischemia, and pretreatment with EA prevented this reduction; and 3) MDA level and heart rate was increased by GCIR and pretreatment with EA reduced MDA level and restored the HR to normal level. CONCLUSION: Results indicate that global cerebral ischemia-reperfusion impairs certain heart functions and ellagic acid as an antioxidant can restore these parameters. The results of this study suggest the possible utility of ellagic acid in patients with brain stroke.

Spasmogenic Activity of the Seed of Terminalia chebula Retz in Rat Small Intestine: In Vivo and In Vitro Studies.

BACKGROUND: Terminalia chebula Retz is traditionally used to relieve constipation. The current study was performed to investigate the pharmacological action of aqueous extract of Terminalia chebula seeds (ATC) in vitro and in vivo. METHODS: Terminal pieces of rat ileum were suspended in organ bath containing Tyrode solution. The ileum spontaneous motility frequency and contractility were recorded isotonically. To induce ileal contraction, carbachol and ATC were added to the organ bath. In addition, the effect of hexamethonium, indomethacin, atropine, and verapamil on the ATC-induced ileal contractions was also investigated. The effectiveness of ATC on relieving morphine-induced constipation was investigated in an in vivo study by measuring the faecal number, faecal water content, and intestinal transit ratio. RESULTS: ATC increased the frequency of ileum motility and tension of contraction dose-dependently (P < 0.05). Responses induced by ATC were inhibited by pre-treatment of the tissue with verapamil. The ATC activities were not affected by atropine, hexamethonium, and indomethacin. The faecal number and faecal water content were increased dose-dependently by ATC (P < 0.05). CONCLUSION: The excitatory effects of ATC on ileal contractile frequency and tension are possibly mediated through Ca(2+) channels activation. The results of the present study support the traditional usage of ATC for the treatment of constipation.

Evaluation of the antidiabetic and antilipaemic activities of the hydroalcoholic extract of phoenix dactylifera palm leaves and its fractions in alloxan-induced diabetic rats.

BACKGROUND: The antidiabetic and antilipaemic effects of Phoenix dactylifera leaf extract (PDE) and its fractions were investigated in various rat models. METHODS: Diabetes was induced in male Wistar rats by alloxan monohydrate. Diabetic animals were randomly divided into 8 groups (1 diabetic control and 7 treated groups). Diabetic control animals received saline (5 mL/kg) orally, whereas the treatment groups received different doses of PDE (100, 200, and 400 mg/kg), PDE fractions (50, 100, and 200 mg/kg), or glibenclamide (4 mg/kg) orally once a day for 14 days. Blood was withdrawn for glucose determination on the 1(st), 6(th), 10(th), and 14(th) days. The rats were fasted overnight and then sacrificed on the 14(th) day; blood was collected for biochemical evaluation, including the levels of blood glucose, plasma insulin, serum triglyceride, and cholesterol. RESULTS: Subacute administration of PDE or its fractions in alloxan-induced diabetic rats significantly reduced blood glucose (P < 0.01). Water intake, serum triglyceride, and cholesterol also decreased in treated animals compared with the control group (P < 0.01). Plasma insulin level increased in the treated groups relative to the control group (P < 0.01). CONCLUSION: The results suggested that PDE exhibits antidiabetic and antilipaemic effects in alloxan-induced diabetic rats.

Antispasmodic effect of Piper nigrum fruit hot water extract on rat ileum.

The aim of this study was to investigate the effect of black pepper fruit hot water extract (BPE) on rat ileum contractility and the mechanism(s) of its action. The extract was prepared by adding black pepper powder to boiling distilled water followed by evaporated the solvent. Ileum was dissected from male adult rat (Wistar) and in Tyrode solution the tissue contractions were recorded by an isotonic transducer under 1 g tension. The cumulative concentrations of the BPE (0.0625-1 mg mL(-1)) reduced the ileum contractions induced by KCl (60 mM) or carbachol (10 microM) concentration dependently (p<0.001). In Ca2+-free Tyrode solution with high potassium (60 mM), BPE, (0.0625-1 mg mL(-1)) attenuated the contractions induced by cumulative concentrations of CaCl2 (0.225-2.7 mM) concentration dependently (ANOVA, p<0.05). The incubation of the tissue preparation (20 or 30 min) with L-NAME (100 microM), naloxone (1 microM) or propranolol (1 microM) did not reduce the extract antispasmodic effect on KCl-induced ileum contraction. The extract spasmolytic effect was attenuated neither by glibenclamide (10 microM) nor by tetraethylammonium (1 mM). Present results suggest that the spasmolytic effect of the extract on rat ileum was possibly mediated via Ca2+ influx.

Effect of grape seed extract on lead induced hypertension and heart rate in rat.

The main objective of this study was to evaluate the potential protective effect of red Grape Seed Extract (GSE) on lead induced hypertension (HTN) and Heart Rate (HR) in male Wistar rats. The rats were randomly assigned to one of 4 groups: Each group received lead acetate (100 ppm in drinking water), GSE (100 mg kg(-1), orally) or Lead + GSE for 45 days. Another group assigned as control group provided with tap water and regular pellet food. The Systolic Blood Pressure (SBP) and heart rate were determined by tail plethysmography coupled to a computer system. There was a sustained elevation of SBP in lead exposed rats that significantly increased at day 18 (lead treated, 112.7 +/- 2.7 mmHg, vs. control, 105.6 +/- 2.6 mmHg, n = 10, p < 0.05) and reached a maximum level at day 36 (lead treated, 124.9 +/- 2.3 mmHg, vs. control, 103.6 +/- 3.1 mmHg, n = 10, p < 0.001). However, the other three groups; showed no significant changes in SBP. Furthermore, the heart rate was increased sustainly in lead exposed animals that was statistically significant at days 36 and 45 (lead treated group, 404.5 +/- 9.4 vs. control group, 381.7 +/- 6.7, n = 10, p < 0.05). The blood lead level in both lead and lead + GSE treated groups was increased significantly compared with control and GSE treated groups (p < 0.001). However, GSE administration had no effect on the blood lead level in lead treated group. According to the result of this study, it may be concluded that GSE could have beneficial effect in protecting the cardiovascular system through its antioxidant activity against oxidative stress.

Vasorelaxant and hypotensive effects of Allium cepa peel hydroalcoholic extract in rat.

The aim of present study was to investigate the effect of onion (Allium cepa) peel hydroalcoholic extract (OPE) on rat hypertension induced by high-fructose diet and aorta contractility. The OPE was prepared by maceration method using 70% ethanol. The thoracic aorta from male adult rat (Wistar) was dissected and suspended in Krebs-Henseleit solution under 1 g resting tension. Tissue preparation was contracted by KCl (80 mM) or phenylephrine (Phe, 1 microM) and then the extract was applied cumulatively (0.0625-2 mg mL(-1)). Hypertension was induced in negative control and three groups of rats by adding fructose (10% WN/V) in drinking water for 6 weeks but control group received tap water. Hypertensive groups received saline or OPE at 200, 400 and 800 mg kg(-1) daily for last 3 weeks by gavage. Results showed that OPE reduces aorta contractions induced by KCl or Phe in a concentration-dependent manner (p < 0.001). Removing aorta endothelium did not attenuate the OPE activity. Inhibition of nitric oxide, cGMP and prostaglandin synthesis by L-NAME (100 microM), methylene blue (10 microM) and indomethacin (10 microM), respectively, did not attenuate OPE activity. Atropine abolished ACh-induced relaxation in Phe precontracted aorta but not the OPE-induced relaxation. Although the extract did not change heart rate but after 3 weeks reduced the hypertension induced by fructose (p < 0.001). Present results indicated that OPE reduces aortic contractions possibly via inhibition of calcium influx but without involving NO, cGMP, endothelium and prostaglandins. The OPE hypotensive effect could be due to extract quercetin content, antioxidant activity and inhibiting vascular smooth muscle cells Ca2+ influx.

Ileal relaxation induced by Mentha longifolia (L.) leaf extract in rat.

The effect of Mentha longifolia (L.) leaf hydroalcoholic extract (MLE) was examined on rat ileal smooth muscle contractions. Last portion of ileum from male adult Wistar rat was mounted in an organ bath containing Tyrode solution. The tissue was contracted by carbachol (CCh, 10 microM), KCl (60 mM) and BaC12 (4 mM) and then MLE (0.0625-1 mg mL(-1)) was added to the bath cumulatively. The effect of MLE on KCl-induced contraction was examined after tissue incubation with propranolol (1 microM), naloxone (1 microM) and N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM). The effect of MLE on CaCl2-induced ileal contraction in Ca(2+)-free with high potassium Tyrode solution was also evaluated. The role of potassium channels was examined by ileum incubation (5 mim) with tetraethylammonium (TEA, 1 mM). The results showed that KCl-, CCh and BaCl2-induced ileal contractions were inhibited (p < 0.001) by cumulative concentrations of MLE with the same potency. In addition, MLE (0.25-1 mg mL(-1)) inhibited (p < 0.01) ileal contractions induced by CaCl2 (0.45-2.7 mM) in a concentration-related manner. The antispasmodic effect of MLE was affected neither by propranolol, L-NAME nor by naloxone. The MLE concentration-response curve was shifted to the right (p < 0.05) by tissue incubation with TEA. From results it may be suggested that Mentha longifolia hydroalcoholic leaf extract induces its spasmolytic activity mainly through disturbance in calcium mobilization and partly by potassium channels activation. Present results show that Mentha longifolia leaf extract exerts relaxant effects on intestinal smooth muscle, consistent with the traditional use of the plant to treat gastrointestinal disorders such as diarrhea and colic.

Effect of esophageal distention on basal and stimulated gastric acid secretion in rats.

BACKGROUND: It is well established that the esophageal distention (ED) leads to gastric relaxation, partly by vago-vagal reflex, but till now, the effect of ED on gastric acid secretion has not been investigated. The aim of this study was to investigate the effect of ED on basal and stimulated gastric acid secretion. METHODS: Adult male Wistar rats (200-240 g) were deprived of food but not the water 24 h before the experiments. Under urethane anesthesia (1.2 g/kg, i.p.), animals underwent tracheostomy and laparotomy. A catheter was inserted in the stomach through duodenum for gastric distention and gastric washout and the esophagus was cannulated with a distensible balloon orally to distend esophagus (0.3 ml, 10 min). Gastric acid secretion was stimulated by gastric distention, carbachol (4 microg/kg, i.p.) or histamine (5 mg/kg, s.c.). Effects of vagotomy, NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.v.) and also hexamethonium were investigated. RESULTS: Basal and gastric distention- and carbachol, histamine-stimulated acid secretion were reduced by the ED (P<0.05, P<0.0001, P<0.01 and P<0.02, respectively). L-NAME (10 mg/kg, i.v.) elevated the acid output (P<0.002). Vagotomy reduced the inhibitory effect of the esophagus distention on gastric distention-induced acid secretion (P<0.01). CONCLUSION: These results indicate that the vagus nerves are involved in the inhibitory effect of the ED on the basal and stimulated gastric acid secretion. Furthermore, nitric oxide could be involved.