Clinical Observation And Mechanism Study On The Improvement Of Amnesia In Old Age With Cistanche-san

Objective:To observe the ameliorative effect of Cistanche-San on amnesia in old age and to investigate its mechanism of action.Methods:1.For clinical observation,patients with amnesia in old age who met the inclusion criteria were treated with Cistanche-San as the main formula for a total treatment period of 6 weeks,with reference to the Chinese medical evidence criteria for "forgetfulness" in the Chinese Medicine Internal Medicine,edited by Zhou Zhongying.The clinical efficacy was evaluated by using the Dementia Classification Scale and the Simple Mental State Scale(MMSE)to score the TCM symptoms and memory of the patients before and after the treatment.2.For the experimental study,50 ICR mice were randomly divided into 10 mice each in the sham-operated group,the late-stage AD model group,the Cistanche-San low-dose group,the Cistanche-San high-dose group and the flutamide group.Except for the sham-operated group,all other groups of mice were established as late onset AD animal models by unilateral gonadectomy(testis)and bilateral hippocampal dentate gyrus(DG)Aβ injection.Morris water maze method was applied to evaluate the hippocampal-dependent cognitive function of each group.The expression of the proteins Ki67 and DCX in the hippocampal region of each group of mice was measured by Western-blot.Testosterone(T),luteinising hormone(LH),follicle stimulating hormone(FSH)and gonadotropin-releasing hormone(GnRH)were measured by Elisa.GnRH)concentrations.Results:1.Compared with the pre-treatment period,the MMSE scale scores of the subject patients increased significantly(p<0.01)and the dementia syndrome scale scores decreased significantly(p<0.01)after 6 weeks of treatment,showing a statistically significant difference,indicating that Cistanche-san has significantly improved the symptoms and cognitive impairment in the elderly patients with amnesia due to deficiency of the medulla oblongata,deficiency of the spleen and kidney and phlegm clouding.2.Results of the experimental study:Compared with the sham-operated group,mice with late onset AD model had decreased learning memory ability,accompanied by massive loss of neurons in the DG region of hippocampus,decreased expression of Ki67 and DCX proteins in the DG region of hippocampus and hippocampal region,and decreased concentration of serum T,LH and GnRh(P<0.01).Compared with the late-stage AD model group,the cognitive function of mice in the low and high doses of Cistanches improved,while neuronal loss in the hippocampal region decreased,new neurons detected in the DG region of the hippocampus and Ki67 and DCX protein expression in the hippocampal region increased,and serum T,LH and GnRH concentrations increased(P<0.05),and the intervention effect of Cistanches was dose-dependent.Compared with the high dose group,the mice in the flutamide group showed decreased cognitive function,increased loss of hippocampal neurons and decreased expression of Ki67 and DCX in the DG region of the hippocampus(P<0.05),while serum T,LH and GnRH concentrations were not significantly different(P>0.05).There was no statistically significant difference in serum FSH levels between the groups of mice(P>0.05).Conclusion:1.Cistanche-San has an ameliorative effect on the decline of memory ability in people with senile amnesia,which verifies the statement of the Ming dynasty physician Wang Kentang that "Cistanche-San can be taken for a long time without forgetting in old age" and provides a basis for the early prevention and treatment of senile dementia diseases.2.The unilateral gonadectomy combined with bilateral hippocampal dentate gyrus Aβinjections produced an animal model of late-stage AD with cognitive decline,loss of hippocampal neurons,impaired neuronal regeneration and reduced HPG axis function,effectively simulating the pathophysiological characteristics of amnesia and dementia in old age.3.Cistanche has an ameliorating effect on the cognitive impairment of Aβ1-42 induced late onset AD model mice.Enhancing HPG axis function,increasing serum androgen levels and promoting neuronal regeneration,which in turn exerted neuroprotective effects,were involved in the ameliorative effects of Cistanche japonica on cognitive impairment in the late onset AD model animals(or the population with senile amnesia).