人参皂苷Rg_3及人参皂苷Rh_2在肠道菌群失调大鼠体内的药动学研究  

Pharmacokinetic study on ginsenoside Rg_3 and ginsenoside Rh_2 in gut microbiota dysbiosis rats

作　　者：郭跃龙[1] 钱静[2,3] 狄留庆[2,3] 康安[2,3] 

机构地区：[1]江苏省省级机关医院药剂科,江苏南京210024 [2]南京中医药大学药学院,江苏南京210023 [3]江苏省中药高效给药系统工程技术研究中心,江苏南京210023

出　　处：《中草药》2016年第23期4198-4203,共6页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81202983);江苏高校优势学科建设工程资助项目;江苏高校品牌专业建设工程资助项目(PPZY2015A070)

摘　　要：目的 研究人参皂苷Rg3及其脱糖基代谢物人参皂苷Rh2在林可霉素诱导的肠道菌群失调大鼠体内的药动学特征。方法 建立同时测定大鼠血浆中人参皂苷Rg3及人参皂苷Rh2的LC-MS/MS分析方法，并进行专属性、线性、回收率、准确度、精密度的考察。采用ig林可霉素诱导菌群失调大鼠模型，测定正常大鼠及模型大鼠粪便含水量及β-葡萄糖苷酶活性。正常大鼠及肠道菌群失调大鼠分别ig给予人参皂苷Rg3（20 mg/kg），于不同时间点眼眶取血测定血药浓度。结果 与对照组比较，模型组大鼠粪便含水量显著增加（P〈0.01），β-葡萄糖苷酶活性显著降低（P〈0.01）；大鼠血浆中人参皂苷Rg3的Cmax、AUC0~∞值均有所升高，但不具有显著性差异；而其活性代谢物人参皂苷Rh2的Cmax、AUC0~t值与对照组相比显著降低（P〈0.01）。结论 肠道菌群失调对人参皂苷Rg3的药动学行为影响较小，但显著改变了其活性代谢物人参皂苷Rh2的药动学，可能与菌群失调后导致大鼠肠道菌大幅下降进而影响了人参皂苷Rg3的肠道脱糖代谢有关。Objective The aim of this study was to explore the pharmacokinetics of ginsenoside Rg3 and its deglycosylated metabolite,ginsenoside Rh2 in lincomycin-induced gut microbiota dysbiosis rats after ig administration of ginsenoside Rg3.Methods An LC-MS/MS analytical method was developed and validated to detect ginsenoside Rg3 and Rh2 in plasma of rats.The method was validated by specificity,linearity,lower limits of quantification （LLOQ）,precision,accuracy,matrix effect,recovery,and stability.Lincomycin （orally,5 000 mg/kg,7 d） was selected to induce gut microbiota dysbiosis.The fecal moisture contents and the β-D-glucosidase activity were also assessed in this study.And the plasma samples were collected and analyzed after ig administration of ginsenoside Rg3（20 mg/kg）.Results The results indicated that this method could be used for the determination of the concentration of ginsenoside Rg3 and Rh2 in plasma of rats.The fecal moisture content in rats treated with lincomycin was significantly increased （P〈0.01） and the β-D-glucosidase activity was decreased （P〈0.01） compared with the control rats.The AUC0~∞ and Cmax in gut microbiota dysbiosis rats were increased,while the AUC0~t and Cmax of its active metabolite,ginsenoside Rh2 were significantly decreased （P〈0.01） compared with normal rats.Conclusion The pharmacokinetic profile of ginsenoside Rg3 and Rh2 is changed in gut microbiota dysbiosis rats,which partly relates to the decreased β-D-glucosidase activity.

关 键 词：人参皂苷RG3 人参皂苷RH2 菌群失调 药动学特征 β-葡萄糖苷酶 

分 类 号：R285.5[医药卫生—中药学]