环烯醚萜类化合物在阿霉素肾病大鼠肠道菌中的代谢差异研究  

Study of Metabolic Differences of Iridoids by Intestinal Bacteria from Adriamycin-induced Nephropathic Rat

作　　者：石碧锐 董雅倩 邹威[3] 张彦 姚晖[2] 刘孟华[1] SHI Birui;DONG Yaqian;ZOU Wei;ZHANG Yan;YAO Hui;LIU Menghua(School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,Guangdong 510515,China;Department of Clinical Pharmacy,The Second People Hospital of Foshan,Foshan,Guangdong 528000,China;Hunan Provincial Maternal and Child Health Care Hospital,Changsha,Hunan 410008,China)

机构地区：[1]南方医科大学药学院,广东广州510515 [2]佛山市第二人民医院临床药学科,广东佛山528000 [3]湖南省妇幼保健院药学部,湖南长沙410008

出　　处：《今日药学》2022年第4期278-284,共7页Pharmacy Today

基　　金：广东省基础与应用基础研究基金项目(2021A1515011604)。

摘　　要：目的 以梓醇、京尼平苷、车叶草苷、龙胆苦苷和莫诺苷为代表化合物,考察环烯醚萜类化合物在阿霉素肾病大鼠肠道菌群的代谢产物及代谢途径。方法 通过构建阿霉素肾病模型,在厌氧条件下将5种环烯醚萜单体分别与离体大鼠肠道菌群孵育8,24 h,采用高效液相色谱-四级杆飞行时间质谱(HPLC-Q-TOF-MS)对代谢产物进行定性分析。通过对照品对照、准确分子量、裂解方式等手段,分析推测这5种环烯醚萜在肠道菌的作用下均可发生I相代谢反应,包括水解、氧化、还原、甲基化反应。结果 孵育24 h后,京尼平苷和莫诺苷,其苷元水平相应较高;而梓醇、车叶草苷、龙胆苦苷的原型和苷元均相应较低。京尼平苷、车叶草苷、龙胆苦苷和莫诺苷均检测到含N代谢产物,其水平和孵育时间有关。在该体系中未发现Ⅱ相代谢产物。结论 该结果揭示了5种环烯醚萜类化合物在阿霉素肾病大鼠肠道菌中的代谢差异,为其体内研究及进一步开发提供了依据。OBJECTIVE To investigate the metabolites and metabolic pathways of five representative iridoids compounds of catesol, geniposide, chelidonin, gentipicin and mononoside in the intestinal bacteria from adriamycin-induced nephropathic rat. METHODS After the establishment of adriamycin-induced nephropathic rat model, 5 iridoids were incubated with intestinal bacteria for 8 and 24 h, respectively, under anaerobic conditions. HPLC-Q-TOF-MS was used to identify the metabolites by reference substance control, accurate molecular weight and the fragmentation behavior. Five iridoids could be easily metabolized by rat intestinal bacteria through phase I metabolic reactions, including hydrolysis, oxidation and methylation reaction. RESULTS After incubation for 24 h, the aglycones of geniposide and monoside were relatively high, whereas the response values for prototypes and aglycones of catalpol, asperuloside and gentiopicroside were relatively lower. N-containing metabolites were detected in geniposide, asperuloside, gentiopicroside and mononoside, which were related to the incubation time. In addition, no phase Ⅱ metabolites were found in this system. CONCLUSION The results mainly reveal the metabolic differences of 5 iridoids in the rat intestinal bacteria with adriamycin nephropathy, providing useful data for their application and further development in vivo.

关 键 词：环烯醚萜 阿霉素肾病大鼠肠道菌 代谢 高效液相色谱-四级杆飞行时间质谱 苷元 

分 类 号：R917[医药卫生—药物分析学]