Ability of Tong Luo Jiu Nao Oral Solution to Improve Cognitive and Gait Deficits in a Rat Model of Focal Cerebral Ischemia

Objective To investigate the ability of Tong Luo Jiu Nao(TLJN)Oral Solution to improve cognitive and gait deficits in a rat model of focal cerebral ischemia.Methods An intraluminal suture method was used to create a rat model of focal cerebral ischemia.Experimental animals were divided into4groups:sham surgery,cerebral ischemia model,cerebral ischemia model+low-dose TLJN Oral Solution(150mg/kg),cerebral ischemia model+high-dose TLJN Oral Solution(300mg/kg).After4weeks of drug intervention,water maze and gait analyses were conducted.Brain tissue was stained with hematoxylin and eosin and used to monitor and calculate the volume ratio of cerebral infarction in each group of permanent middle cerebral artery occlusion(pMCAO)rats.Results(1)Gait analyses:TLJN Oral Solution significantly improved the overall gait of the focal cerebral ischemic rat model.The improvement in walking speed might have been achieved by the shortening of the animals’stride time.The shortening of stance time by TLJN in the cerebral ischemic animals might be due to the shortening of brake and propulsion times,while the shortening of stride time by TLJN in the cerebral ischemic animals might have been due to the shortening of stance time and swing time.(2)Water maze navigation test:high-dose TLJN Oral Solution significantly reduced the animals’total swimming distance and duration and increased the proportion of swimming distance and time spent in the target quadrant,suggesting that TLJN significantly improved the cognitive deficit in the animal model.(3)High-dose TLJN significantly reduced the cerebral infarction volume ratio of the pMCAO rats.Conclusion This intraluminal suture method can reliably replicate a rat model of focal cerebral ischemia.TLJN Oral Solution improves the gait and cognitive function of the focal cerebral ischemia rat model to various extents.

Effects of Liuwei Dihuang decoction and its compatible prescriptions on the function of hypothalamus-pituitary-adrenal axis in senescence-accelerated mouse

OBJECTIVE To investigate age-related functional change of hypothalamus-pituitary-adrenal(HPA)axis in senescence accelerated mouse(SAM)and the effects of Liuwei Dihuang decoction(LW)and its San-bu(three tonics)and San-xie(three eliminators)components on the function of HPA axis.METHODS Male SAM-resistance/1(SAMR1)and SAM-prone/8(SAMP8)at the ages of 6and 12 months old were used.SAMP8 were orally administered with LW,three tonics and three eliminators at the doses of 10,6.4and 3.6g·kg-1·d-1,respectively,for consecutive 60 d.Serum level of CORT was assayed with ELISA method.The levels of hypothalamic CRH and pituitary ACTH was determined with radioimmunoassay.RESULTS The levels of hypothalamic CRH,pituitary ACTH and serous CORT were much higher in 6 and 12 months old SAMP8 than those in age-matched SAMR1,which suggested the abnormal function of HPA axis in SAMP8.Oral administration of LW and three tonics significantly decreased the level of hypothalamic CRH of 6 and 12 months old SAMP8,and reduced the levels of pituitary ACTH and serous CORT of 6 month old SAMP8.Three eliminators significantly decreased the level of hypothalamic CRH of 6 months old SAMP8.The results indicated that oral administration of LW,three tonics and three eliminators improved the function of HPA axis of SAMP8.CONCLUSION The results showed the hyperactivity of HPA axis of SAMP8,and LW improved the hyperactivity of 6 month old SAMP8.Three tonics and three eliminators had similar effects as LW,which had better effect after compatibility.

Antidepressant-like effects and memory enhancement of a herbal formula in mice exposed to chronic mild stress

Shen Yuan Gan（SYG） is a Chinese herbal prescription composed of total saponins of Panax ginseng and total oligosaccharide esters of Polygala tenuifolia（2：1）.Our previous studies have demonstrated that SYG has antidepressant-like effects in various mouse models of behavioral depression.The present study aimed to test whether SYG affected chronic mild stress（CMS）-induced depression and cognitive impairment in mice.We found that a 5-week CMS schedule induced significant degradation of the coat state,decreased sucrose intake in the sucrose-preference test,and increased the latency to feed in the noveltysuppressed feeding test.All of these CMS-induced changes were ameliorated by SYG（100 and 200 mg/kg） and fluoxetine（10 mg/kg）.In addition,SYG restored the decreased monoamine neurotransmitter concentrations（serotonin,dopamine,norepinephrine and acetylcholine） induced by CMS in the prefrontal cortex.Interestingly,SYG ameliorated CMS-induced cognitive impairment in the step-through test,and increased the acetylcholine level in the prefrontal cortex.These results suggest that SYG has an antidepressant-like action and enhances cognition by modulating the serotonin,dopamine,norepinephrine,and acetylcholine levels in the prefrontal cortex.