基于黄芪皂苷类成分药代动力学特征解析黄芪皂苷Ⅰ的质控合理性OA
Analysis of rationality of quality control for astragaloside Ⅰ based on pharmacokinetic characteristics of Astragalus saponins
目的 针对环黄芪醇是黄芪皂苷类成分在体内代谢发挥药效的主要活性成分,解析黄芪皂苷类成分的质量控制指标问题.方法 采用高效液相色谱(HPLC)法检测黄芪水提物及总皂苷中主要成分的含量,并分别开展黄芪总皂苷、黄芪皂苷Ⅰ、黄芪皂苷Ⅳ与环黄芪醇小鼠体内药代动力学研究.将C57BL/6J雄性小鼠随机分为黄芪总皂苷组、黄芪皂苷Ⅰ组、黄芪皂苷Ⅳ组、环黄芪醇组与空白组,除空白组外,其余各组灌胃给药剂量均为50 mg·kg-1,空白组灌胃等体积的0.9%氯化钠溶液,各组于给药10、30、90、180、300、480、960、1 440 min后分别取5只小鼠进行处理,收集血清、肝组织及肠内容物,采用超高效液相色谱-静电场轨道阱高分辨质谱联用系统(UHPLC-Q-Exactive Orbitrap HRMS)法测定黄芪皂苷Ⅰ、黄芪皂苷Ⅱ、黄芪皂苷Ⅲ、黄芪皂苷Ⅳ、异黄芪皂苷Ⅰ、异黄芪皂苷Ⅱ、环黄芪醇在各组血清、肝脏、肠内容物样品中的浓度,计算主要药代动力学参数;收集小鼠新鲜粪便,制备肠菌液及灭活肠菌液,开展黄芪皂苷Ⅰ与黄芪皂苷Ⅳ体外肠菌孵育实验,分别收集孵育0、1、3、8、24 h的样本,采用UHPLC-Q-Exactive Orbitrap HMRS分析样本中环黄芪醇及主要皂苷成分的含量.结果 黄芪皂苷Ⅰ在黄芪水提物和总皂苷中的含量均远高于黄芪皂苷Ⅳ,小鼠经口灌胃黄芪总皂苷后血清及肝组织中环黄芪醇暴露量约是黄芪皂苷Ⅳ的2.6倍与10.4倍;黄芪皂苷Ⅰ在体内外代谢转化为环黄芪醇的效率及总量显著高于黄芪皂苷Ⅳ(7.3倍、5.9倍).结论 黄芪皂苷Ⅰ较黄芪皂苷Ⅳ更适合作为黄芪皂苷类成分的质量控制指标成分.
Objective Given that cycloastragenol is the primary active in vivo metabolite of astragaloside compounds,this study aimed to evaluate the suitability of quality control markers for Astragalus saponins.Methods High-performance liquid chromatography(HPLC)was used to quantify the main components in Astragalus aqueous extract and total Astragalus saponins.Pharmacokinetic studies were conducted in male C57BL/6J mice,which were randomly divided into five groups:total Astragalus saponins group,astragaloside Ⅰ group,astragalosideⅣ group,cycloastragenol group,and control group.Each treatment group was administered 50 mg·kg-1 body weight of the corresponding agent via gavage,while the control group received physiological saline.Serum,liver tissue,and intestinal contents were collected at 10,30,90,180,300,480,960,and 1 440 minutes post-administration.Concentrations of astragalosides Ⅰ-Ⅳ,isoastragalosides Ⅰ-Ⅱ,and cycloastragenol were determined using UHPLC-Q-Exactive Orbitrap high-resolution mass spectrometry(HRMS),and pharmacokinetic parameters were subsequently calculated.Additionally,in vitro fecal microbiota incubation assays were performed with astragalosides Ⅰ andⅣ;concentrations of cycloastragenol and the major saponins were measured at 0,1,3,8,and 24 hours using UHPLC-Q-Exactive Orbitrap HRMS.Results In both Astragalus aqueous extract and total Astragalus saponins,the content of astragaloside Ⅰ was significantly higher than that of astragaloside Ⅳ.After oral administration,the exposure of cycloastragenol in serum and liver tissue in the total Astragalus saponins group was 2.6-fold and 10.4-fold higher,respectively,compared with that in the astragaloside Ⅳ group.Astragaloside Ⅰ exhibited a higher metabolic efficiency to cycloastragenol than astragaloside Ⅳ:in vitro,its metabolic efficiency was 7.3-fold higher,and in vivo,its total conversion rate was 5.9-fold greater.Conclusion Compared with astragaloside Ⅳ,astragaloside Ⅰ is a more appropriate quality control marker for Astragalus saponins.
LIU Wei;LI Chunhui;ZHANG Linzhang;CHEN Jiamei;LIU Ping
Institute of Liver Diseases,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China||Key Laboratory of Liver and Kidney Diseases(Ministry of Education)/Shanghai Key Laboratory of Traditional Chinese Medicine,Shanghai 201203,China||Department of Pharmacy,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine/The SATCM Third Grade Laboratory of Traditional Chinese Medicine Preparations,Shanghai 201203,ChinaInstitute of Liver Diseases,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China||Key Laboratory of Liver and Kidney Diseases(Ministry of Education)/Shanghai Key Laboratory of Traditional Chinese Medicine,Shanghai 201203,ChinaInstitute of Liver Diseases,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China||Key Laboratory of Liver and Kidney Diseases(Ministry of Education)/Shanghai Key Laboratory of Traditional Chinese Medicine,Shanghai 201203,ChinaInstitute of Liver Diseases,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China||Key Laboratory of Liver and Kidney Diseases(Ministry of Education)/Shanghai Key Laboratory of Traditional Chinese Medicine,Shanghai 201203,ChinaInstitute of Liver Diseases,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China||Key Laboratory of Liver and Kidney Diseases(Ministry of Education)/Shanghai Key Laboratory of Traditional Chinese Medicine,Shanghai 201203,China||Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine/Shanghai Chemical Biology of Frontier Base of Traditional Chinese Medicine,Shanghai 201203,China
黄芪皂苷类成分黄芪皂苷Ⅰ黄芪皂苷Ⅳ环黄芪醇中药质量控制
Astragalus saponinsastragaloside Ⅰastragaloside ⅣcycloastragenolChinese materia medicaquality control
《上海中医药杂志》 2026 (1)
73-81,9
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