Prediction and partial verification of potential target proteins of saikosaponins and their metabolites / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To study saikosaponins (SSs) and their metabolites (a total of 30 compounds) in order to predict and verify partially potential target proteins. METHODS ①PharmMapper and Sybyl X were used to predict potential target proteins of SSs and their metabolites,and the binding model of saikosaponin a (SSa) and glutathione s-transferase A2 (GST A2) was investigated. ② In vitro experi?mentsHepRG cells were treated with SSa 0,0.03,0.06,0.13,0.25 and 0.50 mmol·L-1for 24 h,and cell viability was detected by CCK-8 analysis. HepaRG cells were treated with SSa 0, 0.03, 0.13 and 0.50 mmol·L-1for 24 h, and GST activity was detected. RESULTS ① PharmMapper and Sybyl X predicted the potential target proteins of SSs and their metabolites,including GST A2,phosphatidylcholine transfer protein, adenosine kinase, thymidylate synthase, estrogen receptor β, estradiol 17-beta-dehy?drogenase 1,proto-oncogene serine/threonine-protein kinase Pim1,bile acid receptor and cellular reti?noic acid-binding protein 2. The prediction results showed that SSa and GST A2 had the highest total score and a well-matched binding model, so they were most likely to interact. ② In vitro experimentsSSa could inhibit HepaRG cell viability in a concentration-dependent manner (R2=0.8848,P<0.05).Significant increases in activity of GST were observed after treatment with SSa. CONCLUSION The potential target proteins of SSs and their metabolites are GST, phosphatidylcholine transfer protein etc. GST may be one of the target proteins of SSa.