A Study On The Anti-Parkinson’s Disease Dementia Effect Of2,3-indolinedione

Objective:The dementia model was built by scopolamine, the Morris water maze as a device to investigate the effect of2,3-indolinedione (ISA) on the ability of learning and memory of dementia mice;the Parkinson’s disease model was built by arecoline,ISA was preadmini-strated to mice, the duration and latent time of tremor were recorded.The results obtained by these two experiments to prove the anti-Parkinson’s disease dementia effect of ISA.Methods:1. The effect of ISA on the ability of learning and memory of dementia miceHealthy mice were randomly divided into seven groups:control group(physiological saline,10ml·kg-1),model group, selegiline group(lmg·kg-1), piracetam group(300mg·kg-1), three ISA treatment groups, which are defined as mice with three distinct doses (25mg·kg-1,50mg·kg-1,100mg·kg-1). Mice in seven groups were administered once a day for a continuous twenty-eight days period.From the fifteenth day,mice began to receive the training to search platform, until the twenty-second day, scopolamine was used to build the dementia model and began to do the experiment test by the Morris water maze,the escape latency and total distance were recorded.The time of testing is five days. At the twenty-seventh day,the experiment of the Morris water maze was stopped.At the twenty-eighth day,the platforms were removed,the number of through platforms, the distance and swim time of platform quadiant were recorded.2. The effect of ISA on the duration and latent time of tremor of PD miceHealthy mice were randomly divided into seven groups:control group(physiological saline,10ml·kg-1), solvent group(1.25%gummi tragacanthae), model group, selegiline group(10mg·kg-1), three ISA treatment groups, which are defined as mice with three distinct doses(25mg·kg-1,50mg·kg-1,100mg·kg-1). Mice in seven groups were administra-ted once a day for a continuous fourteen days period. After24hours of the last administra-tion, arecoline25mg·kg-1was used to build the dementia model and the duration and latent time of tremor were recorded. 3. The study on acute toxicity of ISAMice were randomly divided into five groups(10mice per group), each group was administrated i.g.in a volume0.5ml per mouse.The amount of survival and death mice were observed,the death rate and the value of LD50were calculated.Results:1. After scopolamine was administered,the escape latency and total distance of the model group were remarkably prolonged (P<0.01).During the testing time, the escape latency and total distance in mice treated with the selegiline group,piracetam group and ISA group(50mg·kg-1) were reduce campared to that in the model group(P<0.05), these three groups improved the ability of learning of dementia mice without significant difference. The escape latency and total distance in mice treated with ISA25mg·kg-1and100mg·kg-1had no significant difference campared to that in the model group.2. After the platforms were removed, the number of through platforms, the distance and swim time of platform quadrant in mice treated with the selegiline group,piracetam group and ISA group(50mg·kg-1) were longer than the model group(P<0.05), these three groups improved the ability of memory of dementia mice without significant difference. the number of through platforms, the distance and swim time of platform quadrant in mice treated with ISA25mg·kg-1and100mg·kg-1had no significant difference campared to that in the model group.3. Arecoline induced the tremor on mice (p<0.01); Compared with model group,the duration time of tremor in mice treated with the selegiline group and ISA groups (25mg·kg-1and50mg·kg-1) were longer (p<0.01), but ISA25mg·kg-1and50mg·kg-1had no significant difference compared to that in the selegiline group (p>0.05)。4. Arecoline prolonged the latent time of tremor (p<0.01); Compared with model group,the latent time of tremor in mice treated with the selegiline group were longer (p<0.01); ISA25mg·kg-1prolonged the latent time of tremor too, but had no significant difference campared to that in the model group (p>0.05)。5. LD50of ISA was2.0546(1.6574～2.5496) g·kg-1(95%confidence limit)Conclusions:1ISA could improve the ability of learning and memory of dementia mice treated with scopolamine and had no significant difference campared with positive drugs.2ISA could reduce the duration and latent time of tremor of mice treated with arecoline.3ISA had the effect of anti-PDD and the acute toxicity study showed a very low toxicity of ISA. By means of comprehension and analysis of former research achieve-ments,the mechanism of ISA induced anti-PDD by its activities of actiong on the monoamine transmitters,as MAOI,anti-inflammatory, antioxidant,anti-aging and cardio-vascular protective effect.