Analysis of Metabolic Pathway of Hepatotoxicity Effect of Prepared Aconiti
Objective:To explore the metabolic pathway analysis based on the metabolomics technique to detect the effects of prepared Aconiti on liver function indexes and liver histopathology in rats.Methods:The rats were ran-domly divided into 4 groups according to their body weight.According to the pre-test results,normal group,high dose group,medium dose group and low dose group were set up.In addition to the normal group,the other drug administra-tion groups were given corresponding drug solution once a day for continuous gavage for 28 days.After the last admin-istration,serum samples were collected to detect serum biochemical indexes and the changes of serum endogenous me-tabolites were analyzed by LC-MS non-targeted metabolomics technology.Results:The results of serum biochemical indexes showed that ALT content in high dose group was significantly increased compared with that in the normal group,with statistical significance(P<0.05);There was no significant difference between the two groups(P>0.05).Liver histopathological examination showed that in the normal group,the structure of hepatic lobules was clear,hepato-cyte cords and hepatic blood sinuses were roughly arranged radially,hepatocytes were round and full,and hepatic plates were arranged regularly and neatly.Hepatocyte edema,vacuolation and loss of structural integrity were widespread in the high dose group.No obvious abnormality was found in the middle and low dose groups.A total of 34 endogenous differential metabolites were screened from serum,including 15 up-regulated and 19 down-regulated,most of which involved niacin and various amino acid metabolism.Conclusion:It is clear that prepared Aconiti has certain hepatotox-icity and the mechanism of hepatotoxicity is mainly related to the metabolism of niacinamide(NA)and 1-methylnico-tinamide(MNA).