Clinical Study Of Zhixinkang Capsule On Cognitive Impairment And Experimental Research Of Its Effect On ApoE Knockout Mice

Objectives To observe the intelligence-improving effect of Zhixinkang capsule on cognitive impairment displayed by patients of vascular dementia(VD), mild cognitive impairment(MCI), and Apolipoprotein-E knockout (ApoEKO ) mice, and to study the underlying mechanism.Methods In clinical resarch, MCI and VD patients were treated with Zhixinkang capsule or Hydergine. Neuropsychological tests were used to evaluate activities of daily living (ADL) and cognition. Blood samples were collected to meaure the serum levels of lipids, and to analyze the genotypic frequencies of ApoE. In animal experiment, grown ApoE knockout (ApoEKO) mice were administrated with Zhixinkang capsule and/or Vitamin E. Morris water maze and step-down test were used to evaluate the learning and memory behavior of mice. Both juvenile and grown mice were decapitated after behavioral observation. Biochemical targets were tested to evaluate the condition of oxidative stress. Immunohistochemistry staining and microscopy were used to find cholinergic impairment.Results (一)clinical part one: 1.Cognitive improvement was observed in Zhixinkang group, while not in Vitamin E group. There was synergistic reaction between Zhixinkang and Vitamin E. 2. Hyperlipidemia was retated to MCI. Improvement of lipid metabilism was observed in Zhixinkang group, while not in Vitamin E group. 3.E3/3 was still the most common genotype in MIC patients. Compared with nomal people, the frequency of E3/3 genotype was reduced and the frequency ofε4 allele was increased in MCI patients. 4.ε4 allele frequency of MCI patients with Hyperlipidemia was much more than that of MCI patients without Hyperlipidemia. While the lipid levels were increased in the MCI patients withε4 allele. (二)clinical part two: 1. Cognition and ADL of VD patients in Zhixinkang group were improved much more than those in control group.2.In improving syndromes of TCM(Taditional Chinese Medicine), the therapeutic effects of Zhixinkang were superior to Hydergine. 3. Hyperlipidemia was one of the important risk factors of VD. The improvement of lipid metabolism and viscosity of VD patients were much better in Zhixinkang group than that in control group. (三) animal research: 1. ApoEKO mice revealed cognitive impairment, which was improved by Zhixinkang. 2.The attenuation of antioxidase activities, and the accumulation of lipid peroxidation products were both detected in ApoEKO brain samples. Zhixinkang was found the ability to alleviate the oxidative changes above. 3.There was cholinergic impairment and loss of neurons and synapses in ApoEKO brain samples. Zhixinkang could mitigate the damage above. 4.The curative effects of Zhixinkang were much better than those of Vitamin E. There was synergistic reaction between Zhixinkang and Vitamin E.Conclusions 1. Zhixinkang could ameliorate the cognitive impairment of patients with MCI or VD. Zhixinkang could improve the syndromes of TCM remarkably. The ability to improve lipid metabolism and blood viscosity was the underlying mechanism probably. 2. ApoEKO mice dispalyed cognitive impairment, as well as oxidative stress and cholinergic damage in brain samples. 3. Zhixinkang could alleviate the impairment above, while the ability of anti-oxidation was the underlying mechanism probably. 4.The curative effects of Zhixinkang were much better than that of Western medicine, while there was synergistic reaction between them.