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Objective To establish an animal model of aging,to observe changes related to cognitive impairment and depression-like behavior,and to explore the mechanisms of the two diseases caused by the model.Methods Male Sprague-Dawley (SD) rats were treated with D-galactose and alchlor;after simultaneous administration of both drugs,their learning and memory abilities were assessed using the Morris water maze test.The depression-like behavioral changes were observed in the forced swimming test.Golgi staining was performed to observe the development of hippocampal neurons;oxidative stress index changes in superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were analyzed in the hippocampus.Results Compared with a control group,rats in the model group showed reduced escape latency (P ＜ 0.05) from the platform in the water maze,reduced residence time on and a reduced number of times passing through the platform (P ＜ 0.05);the real time in the water during the forced swimming test was significantly prolonged (P ＜ 0.01).Golgi staining indicated that dendritic spine density in the hippocampus in model rats was decreased (P ＜ 0.01),as was hippocampus SOD activity (P ＜ 0.05),while MDA levels were increased (P ＜ 0.05).Conclusion We established a new animal model of aging with cognitive impairment and depression.The common disease mechanisms of these two diseases might be related to the destruction of the nervous system during the process of overload caused by free radicals and the resulting metabolic imbalance.
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Aim To explore the therapeutical effect and mechanism of baicalein on two 6-hydroxydopamine (6-OHDA ) induced Parkinson′s disease (PD ) rat models,which received unilateral lesions of the left medial forebrain bundle (MFB ) or caudate putamen (CPu ) made by stereotaxic injection of 6-OHDA (MFB-M,CPu-M).Methods PD rat models were established by microinjection of 6-OHDA into MFB or CPu.The anti-tremor effect of baicalein on PD rat models was examined.Spontaneous activity was recor-ded. Dopamine (DA ), dihydroxyphenylacetic acid (DOPAC)and homovanilic acid (HVA)in striatum were quantified by HPLC-ECD.The tyrosine hydroxy-lase (TH)and OX-42 positive cells were detected by immunohistochemical method.The morphological vari-ation of the neurons was confirmed by analysis at an ul-trastructural level.Results Baicalein significantly in-creased the spontaneous activity in CPu-M.The elec-tromyography (EMG ) recordings revealed that com-pared with 6-OHDA group,the tremor frequency in ba-icalein group was decreased by 55% in MFB-M,and by 60% in CPu-M.6-OHDA treatment decreased DA levels in the striatum,while treatment with baicalein attenuated the DA decreases in CPu-M.Moreover,ba-icalein treatment could increase TH-positive neurons and decrease OX-42-postive microglia compared with 6-OHDA group in both MFB-M and CPu-M.Conclu-sions In the present study,it is illustrated that ①microinjection of 6-OHDA into the MFB and the CPu could cause different pathological changes of PD, which is important for efficacy evaluation;②baicalein showed the ability to alleviate the behavior symptoms in PD-rats at different stages by improving motor function and attenuating muscle tremor;③therapeutic effect of baicalein was produced by inhibiting the inflammatory medium production and release,anti-apoptosis,chan-ging dopamine catabolism, and inhibiting dopamine turnover.
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To investigate the effects of the effective component group of Xiaoxuming Decoction (XXM), a compound traditional Chinese herbal medicine, on cerebral mitochondria in rats with chronic cerebral ischemia.
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Objective To develop and validate a simple,rapid,sensitive,and reproducible HPLC method for simultaneous determination of baicalein and its metabolite baicalin in dog plasma and for the subsequent pharmacokinetic study after iv administration to dogs.Methods An accurate and reproducible HPLC-UV method was developed and validated for simultaneous determination of baicalein and baicalin in dog plasma,using luteolin as internal standard.The analytes were separated by an Agilent Zorbax SB-C column(250 mm×4.6 mm,5μm)and the column temperature was maintained at 40 ℃.The mobile phase was a binary mixture of acetonitrile and water(27:73),containing 0.05% phosphoric acid in water,with a flow rate of 1.0 mL/min.The UV detector was set al 276 nm.Results Linear relationships were validated over the range of 0.05-25 μg/mL for baicalein and 0.05-20 μg/mL for baicalin.The intra-and inter-day precision values for all samples were within 8.0%,using relative standard deviation.This method was successfully applied to the pharmacokinetic studies in dogs after iv administration of baicalein.Baicalein was converted to baicalin quickly.Cmax values were 21.13 μg/mL at 0.05 h for baicalein and 1.57 μg/mL at 0.5 h for baicalin,areas under the plasma concentration-time curve were 4.97 h.μg/mL for baicalein and 0.63 h.μtg/mL for baicalin,and the elimination half-life is 0.50 h for baicalein and 0.75 h for baicalin,respectively.Conclusion The method is able and sufficient to be used in drug metabolism and pharmacoklnetic studies of baicalein.