HPLC-Q-TOF-MS/MS分析大承气汤在人肠道菌群中的代谢产物  

Identification of Metabolites of Da Chengqi Tang in Human Intestinal Microflora in Vitro by HPLC-QTOF-MS/MS

作　　者：刘兴艳 马舒伟[2] 黄玉凤 李丽[3] LIU Xingyan;MA Shuwei;HUANG Yufeng;LI Li(Ningbo Polytechnic,Ningbo 315800 Zhejiang,China;Zhejiang Pharmaceutical College,Ningbo 315100 Zhejiang,China;China Pharmaceutical University,Nanjing 210009 Jiangsu,China)

机构地区：[1]宁波职业技术学院,浙江宁波315800 [2]浙江医药高等专科学校,浙江宁波315100 [3]中国药科大学,江苏南京210009

出　　处：《中药新药与临床药理》2021年第7期1004-1011,共8页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：浙江省自然科学基金项目(LQ21H280001);浙江省教育厅一般课题(Y201941130);宁波市自然科学基金项目(2019A610373)。

摘　　要：目的鉴别大承气汤在人离体肠道菌群中的体外代谢产物。方法应用高效液相色谱-四极杆飞行时间质谱(HPLC-Q-TOF-MS/MS)鉴别大承气汤体外肠道菌群孵育样品中的代谢产物并推测其转化途径,定量分析其主要成分在48 h内的动态变化情况。结果从大承气汤中鉴别出48个固有的化学成分、21个代谢产物。大承气汤在肠道菌中发生去糖基化、糖基化、甲基化、羟基化、开环反应和水合反应等多种反应,其中去糖基化是苷类成分的主要转化方式。黄酮类化合物柚皮苷、橙皮苷和新橙皮苷含量下降49.56%、29.25%和90.95%;蒽醌类化合物大黄素、大黄甲醚和芦荟大黄素含量下降66.77%、8.23%和9.74%;新木脂素类成分和厚朴酚及厚朴酚含量下降了60.01%和73.80%;各代谢产物含量明显增加。结论肠道菌群对大承气汤具有广泛的代谢作用,随着孵育时间延长,大承气汤中苷类成分水解,提高了大承气汤的生物利用度,具有更强的泻下、抗炎、抗氧化作用的转化产物在肠道菌代谢过程中富集。Objective This study investigated the biotransformation and metabolic profile of Da Chengqi Tang(DCQT)by human intestinal microflora in vitro.Methods DCQT was anaerobically incubated with human intestinal microflora suspensions for 48 h at 37℃.A liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry(HPLC-Q-TOF-MS/MS)method was developed and applied for rapid identification of the metabolites of DCQT.Results There were 48 compounds identified in DCQT,and 21 metabolites were identified.The possible metabolic pathways,including deglycosylation,glycosylation,methylation,hydration and C ring cleavage of the benzo-γ-pyrone system,were identified.The deglycosylation was the major metabolic pathway of glycosides in DCQT-BT.When DCQT was anaerobically incubated for 48 h by human intestinal microflora,the levels of flavanone glycosides(naringin,hpesperidin and neohesperidin)were decreased continuously(49.56%,29.25%and 90.95%);the levels of anthraquinones(emodin,physcion and aloe-emodin)were decreased continuously(66.77%,8.23%and 9.74%);the levels of honokiol and magnolol were decreased continuously(60.01%and 73.80%).At the same time,the metabolites were increased continuously.Conclusion With incubating time prolonging,extensive metabolism of DCQT by human intestinal microflora in vitro was observed.Biotransformation of DCQT by human intestinal microflora is beneficial to elevate bioavailability of flavonoid glycosides and metabolites may play a key role in activities of DCQT.

关 键 词：人肠道菌群 转化代谢 大承气汤 液相色谱-四极杆飞行时间质谱 泻下 抗炎 抗氧化作用 

分 类 号：R284.1[医药卫生—中药学]