Abstract:To study long-term toxicity of mangiferin and to provide reference for the safety dose of clinical drugs.Methods:Mangiferin was given to Beagle dogs at a dose of 0.2 g/kg,1 g/kg and 4 g/ kg.The control group was given 0.5% CMC-Na once a day,lasting 1 month.To measure body weight once a week,body temperature 1 times,and adjust the dosage according to body weight.The blood,blood biochemistry,blood electrolytes,blood clotting and other tests were performed at the end of administration.Also,the blood samples were collected at the end of the administration.After given anesthesia,take bone marrow smear,and then bleeding dogs to death for autopsy and histopathological examination.At the end of the administration,the remaining 2 dogs in each group were routinely fed for 2 weeks to observe reversibility and delayed toxicity.Results:During the period,the color of the dogs was deepened,but their stool shape,defecation frequency and defecation volume were normal.Other signs including behavioral activities,glandular secretion and feeding did not change obviously.Results:Showed that there was no significant difference between the control group and the experiment group at each time point.The dog heart rate G wave,PR interval,QRS interval,QT interval,ST segment offset were normal.At each time point,compared with the control group,heart rate were of no significant difference,hematology indicators were normal and blood biochemical indicators were normal in the treatment groups.Before and after treatment,eyes light media transparency,retina,blood vessels,optic papilla are basically normal in all groups,and no significant changes was caused by the test sample.Mangiferins were given to Beagle dogs for 1 month,and compared with the control group,the bone marrow hyperplasia was active,the proportion of granulocytes and erythroid nucleated cells,the proportion of granulocytes and erythrocytes,megakaryocyte cell line are all normal.Compared with the control group,bone marrow cells were with no significant abnormalities in all treatment group.Mangiferins were given Beagle dogs for 1 month and recovered for 2 weeks.Compared with the control group,the weight and coefficient of the organs in the treatment group were normal at each time point.The weight and coefficient of testes and epididymis were significantly higher than those of the control group at the end of the experiment (P<0.05).Conclusion:Mangiferin was administered continuously for 1 week and stopped for 2 weeks.There were some scattered lesions in the treatment group,but the lesion was not common and no dose-toxicity relationship was observed.In the control group,it was found that the dose and the target organ of Beagle dogs caused by the test product were positively correlated with the area under the curve,and the long-term oral administration of mangiferin showed a tendency to accumulate in Beagle dogs.The Beagle dogs have a maximum dose limit of 4 g / kg,which is 127 times higher than the clinical recommended dose.Therefore,clinical recommended dose should be safe.