The Mechanism Of Indole-2, 3-dione (ISA) On Anti-aging Effects

Objective Indole-2,3-dione (Isatin ISA) is a new natural marine drug. It has been reported many times that it is a kind of endogenous Type B monamine oxidase (MAO-B) inhibitor, and systemic administration of ISA could exert anti-epileptic, anticonvulsant and anti-senile tremor effects. In order to find the value of using the drug, we studied the long time side-effects and the anti-aging ability of it acting as a Type B monamine oxidase inhibitor.Methods (1)Healthy rats were randomly divided into four groups: one control group, which is defined as rats which are astrogavage-administered with 1.25% west gum tragacanth. Three ISA treatment groups, which are defined as rats with three distinct doses(30mg-kg-1, 150mg-kg-1, 300mg-kg-1) of isatin gastrogavage. Rats in these groups were administered once a day for a continuous-6 months period. When the. drug administration process was completed, a further 24-hour wait was instituted before the rats were killed. The blood serum were provided to test the biochemistry marker, such as MAO-B, SOD et al. Next, the thymus gland, spleen , brain tissue et al were carefully removed and separately weighed, and the organ exponent computed. The spleen, thymus gland and brain pathological section were done. (2)Sixty Kunming mice were randomly divided into six groups. The six groups include a control group in which the mice were astrogavage-administered with 1.25% west gum tragacanth. The remaining five groups were categorized as follows: a model group, mice with D-galactose sc and ig 1.25% west gum tragacanth gastrogavage, a lecithin group, mice with D-galactose sc and ig 100 mg-kg-1 lecithin gastrogavage, and 3 ISA treatment groups defined as mice with D-galactose sc and ig given three distinct doses (50 mg-kg-1, 100 mg-kg-1, 200 mg-kg-1) of isatin gastrogavage. Every mouse in these groups was administered once a day for a continuous 40-day period. When the drug administration process was completed, a further 24-hour wait was instituted before the Y-maze test was operated on each mouse. The test involved testing the ability of learning, writing down the times of learning, and the time taking to complete the response. Followingly the mice were weighed and killed. After that, the thymus gland, spleen and brain tissue were carefully removed and separately weighed.After the weighing, the brain tissue was thoroughly mixed in saline. The contents of SQD, ROS and LF in brain tissues were then assayed for their respective levels.Results (1)The rats were feeded with ISA for 6 months. After that, dissection, separation and weighting of hearts, brains, lungs, thymus glands and spleens took place. Compared with the normal group, the exponents of all above organs have no statistic difference . Pathological changes were not found in pathological section of brain, thymus gland and spleen (2)After feeded with ISA for 6 months, the blood samples of the rats were examined. The content of MAO-B in tested rats reduced significantly (P<0.01).(3) The mice were feeded with ISA for 40d. Compared the model group with the lecithin and ISA treatment groups, it is obvious that the mice in latter two groups exhibited increase in learning and memory abilities. (4)After comparing of the brain, spleen and thymus exponents,obvious differences were found in low-dosage groups (P<0.05). In intermediate and high dosage groups, the differences are even prominent (P<0.01). Between the two drugs, the effect of ISA is better than lecithin (P<0.05). ㏕he mice were feeded with ISA for 40d, compared with the model and control group, the activity of SOD decreased in the brain, while the lever of ROS and LF increased (P<0.01). Compared with the model group, ISA groups marked increase in the activity of SOD and the level of ROS and LF in the brain (P<0.01). It appears that ISA has the effects on anti-oxygenation and anti-aging.Conclusion The previous and present findings show that ISA, has no side- effect and exerts anti-oxygenation and anti-aging effects in the brain of mice through preventing endogenous or exogenous n...