Comparison between the effects of quercetin on seizure threshold in acute and chronic seizure models.

Flavonoids are important constituents of food and beverages, and several studies have shown that they have neuroactive properties. Many of these compounds are ligands for γ-aminobutyric acid type A receptors in the central nervous system. This study aimed to investigate the anticonvulsant effects of quercetin (3,3',4',5,7-pentahydroxyflavone), which is a flavonoid found in plants, in rats treated with pentylenetetrazole in acute and chronic seizure models. Single intraperitoneal administration of quercetin did not show anticonvulsive effects against acute seizure. Similarly, multiple oral pretreatment with quercetin did not have protective effects against acute seizure. However, multiple intraperitoneal administration of quercetin (25 and 50 mg/kg) significantly increased time to death compared with the control (p < 0.001). However, quercetin pretreatment had no significant effects on the pattern of convulsion development during all periods of kindling. But on the test day, quercetin (100 mg/kg) could significantly increase generalized tonic-clonic seizure onset (GTCS) and decrease GTCS duration compared with the control (p < 0.01, p < 0.05). We conclude that quercetin has a narrow therapeutic dose range for anticonvulsant activities in vivo, and it has different effects on the seizure threshold. The different effects of quercetin on seizure threshold may occur through several mechanisms.

Effects of quercetin on oxidative stress and memory retrieval in kindled rats.

Flavonoids are a class of polyphenolic compounds present in fruits and vegetables. Several studies have demonstrated a relationship between the consumption of flavonoid-rich diets and the prevention of human diseases including neurodegenerative disorders. Thus, we assessed the effect of quercetin (3,3',4',5,7-pentahydroxyflavone) on oxidative stress and memory retrieval using a step-through passive avoidance task in kindled rats. Quercetin (25, 50, and 100 mg/kg) was administered intraperitoneally (i.p.) before pentylenetetrazole (PTZ) every other day prior to the training. Retention tests were performed to assess memory in rats. Compared to control, pretreatment with 50 mg/kg of quercetin could attenuate seizure severity from the beginning of the kindling experiment by lowering the mean seizure stages. Moreover, quercetin 50 mg/kg significantly increased the step-through latency of the passive avoidance response compared to the control in the retention test. Malondialdehyde (MDA) levels were significantly increased in the quercetin groups compared to the PTZ group in the hippocampus and cerebral cortex following PTZ kindling. In the quercetin groups, higher sulfhydryl (SH) contents were not observed compared to the PTZ group. These results indicate that quercetin at a specific dose results in decreased seizure severity during kindling and performance improvement in a passive avoidance task in kindled rats. All doses of quercetin led to increased oxidative stress in the hippocampi and cerebral cortices of kindled rats.

Effects of vitexin on scopolamine-induced memory impairment in rats.

Various synthetic derivatives of natural flavonoids are known to have neuroactive properties. The present study aimed to investigate the effects of vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), a flavonoid found in such plants as tartary buckwheat sprouts, wheat leaves phenolome, Mimosa pudica Linn and Passiflora spp, on scopolamine-induced memory impairment in rats. To achieve this goal, we assessed the effects of vitexin on memory retrieval in the presence or absence of scopolamine using a step-through passive avoidance trial. In the first part of the study, vitexin (25, 50, and 100 microM) was administered intracerebroventricularly (i.c.v.) before acquisition trials. In the second part, vitexin, at the same doses, was administered before scopolamine (10 microg, i.c.v.) and before the acquisition trials. During retention tests, vitexin (100 microM) in the absence of scopolamine significantly increased the step-through latencies compared to scopolamine. In addition, vitexin (100 microM) significantly reversed the shorter step-through latencies induced by scopolamine (P < 0.05). These results indicate that vitexin has a potential role in enhancing memory retrieval. A possible mechanism is modulation of cholinergic receptors; however, other mechanisms may be involved in its effects in acute exposure.

The effects of rutin on the development of pentylenetetrazole kindling and memory retrieval in rats.

Individuals with epilepsy often complain about memory deficits. Various synthetic derivatives of natural flavonoids are known to have neuroactive properties. Rutin is a flavonoid that is an important dietary constituent of foods and plant-based beverages. The aim of the present study was to investigate the effects of rutin on memory retrieval in pentylenetetrazole (PTZ)-kindled rats using a step-through passive avoidance task. We administered rutin and PTZ intraperitoneally every other day prior to the start of training. Two retention tests were subsequently performed to assess memory in these rats. The results suggest that pretreatment with rutin at 50 and 100mg/kg can attenuate seizure severity during the kindling procedure. Furthermore, rutin administration significantly increased the step-through latency in the passive avoidance paradigm. Taken together, these results indicate that rutin has a potential role in enhancing memory retrieval in kindled rats.

Effects of Urtica dioica extract on lipid profile in hypercholesterolemic rats.

OBJECTIVE: To investigate the effects of extract of Urtica dioica, a perennial herb in Iran, on lipid profile in hypercholesterolemic rats. METHODS: The effects of Urtica dioica extract were tested by using it as a supplement in a high-cholesterol diet. Male rats were fed a high cholesterol diet (10 mL/kg) for 4 weeks with Urtica dioica extract (100 or 300 mg/kg) or 10 mg/kg lovastatin supplementation to study the hypocholesterolemic effects of Urtica dioica on plasma lipid levels, hepatic enzymes activities, and liver histopathological changes. RESULTS: Urtica dioica extract at 100 and 300 mg/kg significantly reduced the levels of total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) and also markedly decreased liver enzymes and weight in animals with a high cholesterol diet. Hematoxylin and eosin staining showed that in the 100 mg/kg extract of Urtica dioica group, the appearance of the liver cells was similar to the control group, and steatosis and inflammation were not found. In the 300 mg/kg extract of Urtica dioica group, mild steatosis was observed but mononuclear inflammatory infiltration was not found. CONCLUSION: The hepatic histopathological results reflect the correlation of Urtica dioica extract with both liver weight and the levels of plasma TC and LDL-C. These results indicate that Urtica dioica extract has hypocholesterolemic effects in the animal model.

Rutin activates the MAPK pathway and BDNF gene expression on beta-amyloid induced neurotoxicity in rats.

Flavonoids are present in foods such as fruits and vegetables. A relationship between the consumption of flavonoid-rich foods and prevention of human disease including neurodegenerative disorders has been demonstrated. We assessed the effect of rutin (3,3',4',5,7-pentahydroxyflavone-3-rhamnoglucoside) on the mitogen-activated protein kinase (MAPK) pathway, memory retrieval and oxidative stress in rats injected with ß-amyloid (Aß), which is implicated to have an important role in Alzheimer's disease (AD). Aß was injected bilaterally in the deep frontal cortex of rat brain. Next, rutin and saline were injected (i.p.) for 3 weeks. In comparison to the control group, rutin significantly increased extracellular signal-regulated protein kinase 1 (ERK1), cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus of rats. Rutin (100 mg/kg) significantly increased memory retrieval compared to the control group. Malondialdehyde (MDA) level in the hippocampus of the rutin group was significantly lower than those in the control group. The content of sulfhydryl groups in the rutin group was higher than that in the control group. The findings show a possibility that rutin may have beneficial effects against neurotoxicity of Aß on memory in rats.

Effects of rutin on oxidative stress in mice with kainic acid-induced seizure.

OBJECTIVE: Flavonoids are present in foods such as fruits and vegetables. Several studies have demonstrated a relationship between the consumption of flavonoid-rich foods and prevention of human disease, including neurodegenerative disorders. We assessed the effect of rutin (quercetin-3-O-rutinoside) on oxidative stress in kainic acid (KA)-induced seizure. METHODS: Thirty-six BALB/c mice were randomly divided into three groups. In the control group, saline (intra-peritoneal, i.p.) was administered for 7 d, and on the last day, KA (10 mg/kg, i.p.) was injected 30 min after administration of saline. In rutin groups, mice were pretreated with rutin (100 and 200 mg/kg, i.p.) for 7 d, and on the last day, KA (10 mg/kg, i.p.) was injected 30 min after administration of rutin. Subsequently, behavioural changes were observed in mice. Lipid peroxidation and oxidative stress were measured respectively in the early and late phases after KA-induced seizures. RESULTS: Seizure scores in the rutin groups were significantly lower than those in the control group (P < 0.01). Furthermore, rutin dose-dependently inhibited the number of wet-dog shakes (WDS) (P < 0.05). Malondialdehyde level in the hippocampus of the rutin groups was significantly lower than that in the hippocampus of the control group on days 1 and 21 after KA administration. In the rutin groups, the thiol levels observed on day 1 after KA administration were higher than that in the control group (P < 0.01). CONCLUSION: These results indicate that rutin has potential anticonvulsant and antioxidative activities against oxidative stress in KA-induced seizure in mice.

Neuroprotective effects of vitexin, a flavonoid, on pentylenetetrazole-induced seizure in rats.

Flavonoids are important constituents of food and beverages and have several neuropharmacological activities. Many of these compounds are ligands for γ-aminobutyric acid type A receptors in the central nervous system. This study aimed to investigate the anticonvulsant effects of intracerebroventricularly administered vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), a flavonoid found in plants, in rats treated with pentylenetetrazole (90 mg/kg, intraperitoneally) and to clarify the underlying mechanism. Vitexin (100 and 200 µm, i.c.v) affected minimal clonic seizures and generalized tonic-clonic seizures induced by pentylenetetrazole by increasing the seizure onset time. Pretreatment with flumazenil suppressed the anticonvulsant effects of vitexin during the onset of both the seizures. These results indicate that vitexin has anticonvulsant effects in the brain, possibly through interaction at the benzodiazepine site of the γ-aminobutyric acid type A receptor complex.

Hepatoprotective Property of Oral Silymarin is Comparable to N-Acetyl Cysteine in Acetaminophen Poisoning.

BACKGROUND: N-Acetyl Cysteine (NAC) is usually used as antidote for prevention of acetaminophen-induced hepatotoxicity. In present study we have evaluated efficacy of oral silymarin in its prevention in rats intoxicated with lethal dose of acetaminophen. METHODS: A total of 50 Male Sprague-Dawley rats were randomly divided into five groups. The first group received only vehicle of acetaminophen and served as control. The second group was given 800 mg/kg acetaminophen by gavage with an orogastric canula. The third, fourth and fifth groups were given 300 mg/kg NAC and 150 and 300 mg/kg silymarin respectively. Analysis of serum AST, ALT, and ALP and liver histopathology were employed for assessment of hepatotoxicity. RESULTS: Mean serum ALT levels were significantly increased in the APAP group rats. The mean serum ALT levels returned to normal in both NAC treated and silymarin treated groups. Silymarin (150 mg/kg) had prevented hepatocytes necrosis similar to NAC. No severe hepatotoxicity were seen in groups 3 and 4; while it is seen in 70% of animals in group 2. CONCLUSION: We found that a single dose of orally administered silymarin (150 mg/kg) significantly attenuated acetaminophen-induced liver damage in rat. Oral silymarin can be used in these patients instead of NAC.

Effects of rutin on lipid profile in hypercholesterolaemic rats.

Rutin (3, 3', 4', 5, 7-pentahydrohyflavone-3-rhamnoglucoside) is a flavonoid of the flavonol type. Rutin is found in many plants and is also an important dietary constituent of food and plant-based beverages. Rutin has several pharmacological properties including antioxidant and cardioprotective activities. Also, it was identified that rutin is the major low-density lipoprotein (LDL) antioxidant compound of mulberry in an in vitro study. The effects of rutin were tested by using it as a supplement in a high-cholesterol diet. Male rats were fed a high-cholesterol diet (1 ml/100 g) for 4 weeks with rutin (10 or 100 mg/kg) or rutin 100 mg/kg and lovastatin supplementation to study the hypocholesterolaemic effects of rutin on plasma lipid levels, hepatic enzyme activity, and liver tissue. Feeding the animals a high-cholesterol diet resulted in marked hypercholesterolaemia and increased the serum level of LDL cholesterol (LDL-C). Rutin (at 100 mg/kg) alone or in combination with lovastatin significantly reduced the levels of total cholesterol, and LDL-C and also markedly decreased liver enzymes and weight in animals with a high-cholesterol diet. Our findings show that 100 mg/kg of rutin alone or with lovastatin supplementation lowered liver weight and enzymes as well as plasma total cholesterol and LDL. The hepatic histopathological results reflect the correlation of rutin and lovastatin combination with both liver weight and the levels of plasma total cholesterol and LDL-C. These results indicate that rutin in combination with lovastatin has increased anti-hypercholesterolaemic effects in an animal model.