目的采用模式生物斑马鱼研究头花蓼有效组分中没食子酸、原儿茶酸的代谢产物及其代谢转化形式,探讨模式生物斑马鱼用于研究药物代谢的可行性及合理性。方法采用UHPLC-Q-TOF/MS联用技术,结合Metabolite Tools(TM)、质量亏损过滤(MDF)等代谢产物分析技术,对各成分暴露于模式生物斑马鱼24 h后的药液以及模式生物斑马鱼体内的代谢产物进行筛查分析。结果没食子酸、原儿茶酸经斑马鱼作用后,主要以甲基化、硫酸化反应为主。在斑马鱼体内外药液检测到没食子酸原形成分和2个甲基硫酸化产物,以及原儿茶酸原形成分、2个甲基硫酸化产物、2个硫酸化产物。结论头花蓼有效组分中没食子酸、原儿茶酸经斑马鱼代谢后存在Ⅱ相代谢产物,这与大鼠体内的代谢机制高度一致,提示斑马鱼对头花蓼有效组分的代谢具有合理性,为阐明该药的药效物质基础提供了实验依据。
Aim Modelorganismzebrafishwasusedto study metabolites and metabolite profile of the gallic acid and protocatechuic acid of effective fractions of Polygonum capitatum,and discuss the feasibility and rationality of the model organism zebrafish in the study ofdrugmetabolism.Methods Thetwocomponents were exposed to model organism zebrafish after 24 h of solution treatment by using ultra-high performance liq-uid chromatography-quadrupole-time-of-flight tandem mass spectrometry technology (UHPLC-Q-TOF MS ) method with mass defect filter (MDF ),and the data was treated with data mining software(Metabolite Tool-sTM).Results Afterzebrafishmetabolism,themain reactions of gallic acid and protocatechuic were methyl-ation sulfated. In addition to the two parent com-pounds,six phase II metabolites were identified,in-cluding four methyl sulfate products and two sulfation products.Conclusions Themetabolismofthegallic acid and protocatechuic acid of effective fractions of Polygonum capitatum by zebrafish presents phase Ⅱmetabolites,which is highly consistent with the meta-bolic mechanism of rats.Thus it indicates the rationali-ty of the methods.At the same time,it also provides the experimental basis for clarifying the substance basis of the drug.