Abstract: This study was to investigate the effects of content variation of major water-soluble components in Dansheninjection on homocysteine (Hcy) metabolism in rats.Acute myocardial infarction (AMI) rats were induced by coronary artery ligation,and then randomly divided into model control,Dansheninjection group,and Dansheninjection with the addition of danshensu (DSS),protocatechuic aldehyde (Pal),salvianolic A (SalA) or salvianolic B (SalB),respectively.Based on plasma concentrations of Hcy and glutathione (GSH),a neural network model was developed to characterize the profiles of Hcy and GSH.Garson algorithm was applied to evaluate the contributions of water-soluble components in Danshen injection on the Hcy and GSH levels.It was shown that the plasma concentration of GSH declined significantly,while the Hcy level increased in AMI rats.After treatment with Dansheninjection, the two indices restored to baseline levels.Compared with those of Danshen injection group,the plasma level of GSH and Hcy were elevated after treatment with Danshen injection added water-soluble components,among which SalA and Pal had the most significant effect,especially within 1 h drug administration.The calculated values by neural network model indicated that the effects of water-soluble components in Danshen injection on the Hcy and GSH were:SalA>Pal≈SalB>DSS,in which the contribution of SalA to the Hcy concentration was most significant.In conclusion, content variation of salvianolic acids in Danshen injection has a distinct effect on the Hcy remethylation and trans-sulphuration pathways, while the underlying mechanisms need to be clarified further.