Antidepressant Effects Of Total Flavone Of Abelmoschus Manihot L. Medic On Post Stroke Depressi On Model And Its Mechanisms

Post stroke depression(PSD) is depression that develops after ischemic stroke.It is a common complication of stroke. Total flavone of Abelmoschus manihot L.Medic (TFA) was extracted from Abelmoschus manihot L.Medic. The essential components of TFA are hyperin, quercetin and other flavonoids. Our former studies indicated that TFA and Hyp have protective effects against cerebral ischemia,and its mechanisms may be related to decrease lipid peroxidation. It has not been reported about the antidepressant effects of TFA.This study is intended to investigate antidepressant effects and possible mechanisms of TFA on PSD rat model. The main results are as following:1 Effect of TFA on PSD rat modelMiddle cerebral artery occlusion(MCAO) 1 hour and reperfusion followed by isolation feed and irritable stimuli was used to induce PSD. The change of body weight,the crossing and rearing score in open-field test and sucrose drinking of PSD rat model were investigated regularly during the whole procedure. TFA (50,100mg/kg,qd×24d) could significant increase the body weight,the consumption of sucrose solution and the crossing and rearing score in open-field test in PSD rats. These findings indicate that TFA could effectively inhibit the depression behavior and show strong antidepressant effect.2 The antioxidation effect of TFA on PSD rat model UV spectrophotometer analysis technique was used to detect the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD),glutathione peroxidase (GSH-Px) in brain homogenate in PSD model rats. TFA(50,100mg/kg,qd×24d) can inhibit the increase of MDA content and increase the activities of GSH-Px in brain homogenate in PSD model rats, TFA(25,50,100mg/kg,qd×24d) could obviously enhance the activities of SOD.These evidences showed TFA have strong antioxidation effect and it may be another important mechanism of its antidepressant effect.3 The improvement of TFA on the indexes of hemorheology on PSD rat model The effects of TFA on the hemorrheology including whole blood viscosity, plasma viscosity,haematocrit (Hct) and erythrocyte deformation were observed.TFA (50,100mg/kg,qd×24d) could reduce the increase of whole blood viscosity at high-middle shear rates and increase the erythrocyte deformation. TFA (100mg/kg,qd×24d) could reduce the increase of whole blood viscosity at low shear rate and plasma viscosity. These results suggested TFA could effectively ameliorate the hemorheological indexes and it may also be another important mechanism of its antidepressant effect.4 The improvement of TFA on HPA axis on PSD rat model Radio-immunity analysis technique was used to detect the plasma levels of adrenocorticotropic hormone (ACTH) and cortisol in PSD model rats. The corticotropin releasing factor(CRF) protein expression was investigated by immunohistochemistry technique in the paraventricular nucleus (PVN) of hypothalamus.The CRFmRNA expression was semiquantified by reverse transcription-chain reaction(RT-PCR) in the hypothalamus. TFA(25,50,100mg/kg,qd×24d) could restore levels of ACTH and cortisol.TFA (50,100mg/kg,qd×24d) could significantly decrease the mean optical density values of CRF positive neurons,downregulate the excessive expression of CRFmRNA.These results suggested TFA could effectively inhibit hyperactivity of the HPA axis,this may be an important mechanism of its antidepressant effect.Conclusion:TFA exhibited antidepressant-like effect on PSD model rats,the mechanisms of it might be associated with its action on antioxidation,improvement on the indexes of hemorheology and inhibition effect on the activating of HPA axis.