Title柴胡皂苷及其代谢产物潜在靶点蛋白预测和部分验证
Other TitlesPrediction and partial verification of potential target proteins of saikosaponins and their metabolites
Authors钟倩雯
朱安
王旗
Affiliation北京大学公共卫生学院毒理学系,北京,100191
北京大学公共卫生学院毒理学系,北京100191
国家中医药管理局中药配伍减毒重点研究室,北京100191
食品安全毒理学研究与评价北京市重点实验室,北京100191
Keywords柴胡皂苷
靶点蛋白
谷胱甘肽S转移酶
saikosaponins
target proteins
glutathione S-transferase
Issue Date2018
Publisher中国药理学与毒理学杂志
Citation中国药理学与毒理学杂志. 2018, 32(2), 105-111.
Abstract目的 以柴胡的主要药效/毒性成分柴胡皂苷(SS)及代谢产物(共30种化合物)为研究对象,预测并验证部分靶点蛋白.方法 ①通过PharmMapper反向分子对接法和Sybyl X正向分子对接预测SS及其代谢产物的潜在靶点蛋白,并预测了柴胡皂苷a(SSa)与潜在靶点蛋白谷胱甘肽S转移酶A2(GST A2)间的结合模式.②体外实验:用SSa 0,0.03,0.06,0.13,0.25和0.50 mmol·L-1处理HepaRG细胞24 h,采用CCK-8法检测细胞存活率;HepaRG细胞用SSa 0,0.03,0.13和0.50 mmol·L-1处理24 h,GST活性检测试剂盒检测细胞GST酶活性.结果 ①PharmMapper和Sybyl X预测SS及代谢产物的潜在靶点蛋白包括:GST A2、磷脂酰胆碱转移蛋白、腺苷激酶、胸苷酸合成酶、雌激素受体、雌二醇17-β-脱氢酶1、原癌基因丝氨酸/苏氨酸蛋白激酶Pim1、胆汁酸受体和维A酸结合蛋白2.预测结果显示,SSa与GST A2之间对接得分最高,二者匹配良好,很可能存在相互作用.②体外实验:SSa能抑制HepaRG细胞存活,呈一定的量效关系(R 2=0.8848,P<0.05);随着SSa浓度升高,细胞内GST活性升高(P<0.01).结论 SS及其代谢产物的潜在靶点蛋白为GST和磷脂酰胆碱转移蛋白等,GST可能是SSa的靶点蛋白之一.
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?ments:HepRG 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 experiments:SSa 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.
URIhttp://hdl.handle.net/20.500.11897/515155
ISSN1000-3002
DOI10.3867/j.issn.1000-3002.2018.02.004
Indexed中国科学引文数据库(CSCD)
Appears in Collections:公共卫生学院

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