Progress in Neuro-Psychopharmacology and Biological Psychiatry
The effects of rutin on a passive avoidance test in rats
Introduction
Rutin (3, 3′, 4′, 5, 7-pentahydroxyflavone-3-rhamnoglucoside) is a flavonoid of the flavonol type that is found in many typical plants, such as buckwheat, passion flower, apples and tea. It is also an important dietary constituent of foods and plant-based beverages (Kuntic et al., 2007).
It has been reported that rutin has several pharmacological properties, including antioxidant, anticarcinogenic, cytoprotective, antiplatelet, antithrombic, vasoprotective and cardioprotective activities (La Casa et al., 2000, Janbaz et al., 2002, Schwedhelm et al., 2003, Sheu et al., 2004, Mellou et al., 2006, Trumbeckaite et al., 2006). Rutin was identified as the major LDL antioxidant compound of mulberry in an in vitro study (Katsube et al., 2006). It displayed anti-hypercholesterolaemic effects in an animal model in combination therapy with lovastatin (Ziaee et al., 2009). Moreover, rutin was found to be a neuroprotective agent (Pu et al., 2007). It has shown anticonvulsant activities in pentylenetetrazol model in rat and mice (Nassiri-Asl et al., 2008) and has also ameliorated ischaemic reperfusion injury in the brain (Gupta et al., 2003). Prolonged supplementation with rutin significantly reversed trimethyltin (TMT)-induced spatial memory impairment and damage to pyramidal neurons in the hippocampal CA3b region. These effects could be related to the antioxidative effects of rutin (Koda et al., 2008). It also suppressed microglial activation and pro-inflammatory cytokines (Koda et al., 2009).
There are several lines of evidence that show fruit- and vegetable-derived phytochemicals, especially flavonoids, have beneficial effects on memory and learning (Spencer, 2007). The effects of flavonoid-rich foods such as gingko biloba, green tea, blueberry, pomegranate juice and pure flavonoids on neuro-cognitive ability have been shown in rodents (Joseph et al., 1999, Hartman et al., 2006, Kim et al., 2004, Yamamoto et al., 2007). Rodent models have been used as models of human declarative memory to predict the potential effects of flavonoids on human cognitive performance (Rendeiro et al., 2009). Previous reports have also established a role for flavonoids in preventing dementia in humans (Commenges et al., 2000). It has been shown that flavonoids can influence peripheral blood flow in human (Schroeter et al., 2006). These vascular effects are potentially significant because increased cerebrovascular function is known to facilitate adult neurogenesis in the hippocampus, based on in vitro study (Gage, 2000). Thus, in this study, we focused on the possible effects of rutin on memory retrieval in rats.
Section snippets
Animals
Male Wistar rats (200–250 g) were obtained from the Razi Institute (Karaj, Iran) and housed in groups of four per cage under standard laboratory conditions. They were kept at constant room temperature (21±2 °C) under a normal 12L:12D regime with free access to food and water. All animal experiments were carried out in accordance with the European Communities Council Directive of 24 November 1986 (86/609/EEC) in such a way as to minimise the number of animals and their suffering.
Drugs
Rutin was
Results
There was no significant difference among the different groups in the number of trials, thus confirming the uniformity of the groups. All the animals reached the criteria during the training procedure. Administration of rutin at doses of 10 and 100 mg/kg daily for one week prior to training induced a significant increase in memory retrieval, compared to the control-treated group in the first retention test (one day after training) (P < 0.01) (Fig. 1). Rutin at a dose of 5 mg/kg also increased the
Discussion
The present study shows that the administration of rutin daily for one week prior to training is followed by enhanced memory retrieval in rats. Rutin (10 mg/kg) significantly increased the retrieval of memory in the first, second and third retention tests of a passive avoidance task compared to control. However, the cognitive-enhancing effect of rutin compared to the control animals was also found at other doses. Furthermore, it seems that rutin (10 mg/kg) impaired extinction compared to other
Conclusion
In our study, one week of rutin administration daily for one week prior to training resulted in an increased retrieval of memory, which was observed in the first, second and third retention tests of passive avoidance test. This effect was more significant when rutin was administered at a dose of 10 mg/kg. It is possible that rutin acts by several mechanisms, mediating a potential role in memory retrieval in rats. Further study is necessary to evaluate the effect of rutin on retention of memory
References (42)
- et al.
Differential effects of flavonols on inactivation of α1-antitrypsin induced by hypohalous acids and the myeloperoxidase-hydrogen peroxide–halide system
Arch Biochem Biophys
(2007) - et al.
Modulation of morphine state-dependent learning by muscarinic cholinergic receptors of the ventral tegmental area
Physiol Behav
(2008) - et al.
Neuroprotective effect of antioxidants on ischaemia and reperfusion-induced cerebral injury
Pharmacol Res
(2003) - et al.
Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease
Neurobiol Dis
(2006) - et al.
Protective effect of rutin on paracetamol- and CCl4-induced hepatotoxicity in rodents
Fitoterapia
(2002) - et al.
Antioxidant flavonol glycosides in mulberry (Morus alba L.) leaves isolated based on LDL antioxidant activity
Food Chem
(2006) - et al.
Protective effect of rutin against spatial memory impairment induced by trimethyltin in rats
Nutr Res
(2008) - et al.
Isocratic RP-HPLC method for rutin determination in solid oral dosage forms
J Pharm Biomed Anal
(2007) - et al.
Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions
J Ethnopharmacol
(2000) - et al.
Neurobehavioral effects of dietary soy phytoestrogens
Neurotoxicol Teratol
(2002)
Membrane cholesterol contents influence the protective effects of quercetin and rutin in erythrocytes damaged by oxidative stress
Chem Biol Interact
Anticonvulsive effects of intracerebroventricular administration of rutin in rats
Prog Neuro-Psychopharmacol Biol Psychiatry
Evidence for up-regulation of brain-derived neurotrophic factor mRNA by soy phytoestrogens in the frontal cortex of retired breeder female rats
Neurosci Lett
Neuroprotective effects of quercetin and rutin on spatial memory impairment in an 8-arm radial maze task and neuronal death induced by repeated cerebral ischemia in rats
J Pharmacol Sci
Comparative study of flavonoids in experimental models of inflammation
Pharmacol Res
The effect of flavonoids on rat heart mitochondrial function
Biomed Pharmacother
Flavonoids with iNOS inhibitory activity from Pogonatherum crinitum
J Ethnopharmacol
Ginkgo biloba extract improves spatial memory in rats mainly but not exclusively via a histaminergic mechanism
Brain Res
Is there a role for estrogen replacement therapy in the prevention and treatment of dementia?
J Am Geriatr Soc
Intake of flavonoids and risk of dementia
Eur J Epidemiol
Encoding, consolidation, and retrieval of contextual memory: differential involvement of dorsal CA3 and CA1 hippocampal subregions
Learn Mem
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