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

Abstract

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 β-amyloid (Aβ), which is implicated to have an important role in Alzheimer's disease (AD). Aβ 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 Aβ on memory in rats.

Keywords: AD; Akt/PKB; Alzheimer's disease; Arc; Aβ; BDNF; CAT; CREB; ERK1/2; GPx; GSH; JNK; MAP kinase; MCAO; MDA; MEK1/2; Memory; Neurotoxicity; PBS; PI3K; PTZ; ROS; Rutin; SH; SOD; TrkB; activity-regulated cytoskeleton-associated protein; brain-derived neurotrophic factor; c-Jun N-terminal kinase; cAMP response element-binding protein; catalase; extracellular signal-regulated protein kinase; glutathione; glutathione peroxidase; i.p.; interaperitoneally; mTor; malondialdehyde; mammalian target of rapamycin; middle cerebral artery occlusion; mitogen activated kinase kinase; mitogen-activated protein kinase; pentylenetetrazole; phosphate buffered saline; phosphatidyl inositiol 3-kinase; protein kinase B; reactive oxygen species; sulfhydryl; superoxide dismutase; tropomyosin receptor kinase B; β-amyloid.