中国中药杂志

2016, v.41(12) 2329-2338

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离体大鼠肠道菌对6种皂苷类成分代谢研究
Metabolism of six saponins by rat intestinal bacteria in vitro

高霞;耿婷;马阳;李艳静;黄文哲;王振中;萧伟;
GAO Xia;GENG Ting;MA Yang;LI Yan-jing;HUANG Wen-zhe;WANG Zhen-zhong;XIAO Wei;Jiangsu Kanion Pharmaceutical Co.,Ltd.;State Key Laboratory of Pharmaceutical New-tech for Chinese Medicine;

摘要(Abstract):

为考察离体大鼠肠道菌群对6种皂苷类成分代谢转化的情况,将6种皂苷类成分单体(三七皂苷R_1,人参皂苷Rg_1,人参皂苷Rg_2,人参皂苷Re,人参皂苷Rd和人参皂苷Rb_1)分别与离体大鼠肠道菌群在厌氧条件下孵育8,24 h,通过乙腈沉淀蛋白和乙酸乙酯萃取处理后,采用LC-Q-TOF-MS/MS对代谢产物进行定性分析。通过比较空白对照样品和加药孵育样品的总离子流以及各个色谱峰的准分子离子和多级碎片离子,分析各皂苷类成分在大鼠粪便中可能的代谢产物。结果发现,大鼠肠道菌群对6种皂苷类成分具有显著的代谢转化作用,三七皂苷R_1主要被代谢为5个产物,代谢途径为三七皂苷R_1→人参皂苷Rg_1→人参皂苷Rh_1和人参皂苷F_1→原人参三醇→脱氢原人参三醇;人参皂苷Rg_1主要被代谢为4个产物,代谢途径为人参皂苷Rg_1→人参皂苷Rh_1和人参皂苷F_1→原人参三醇→脱氢原人参三醇;人参皂苷Rg_2主要被代谢为2个产物,代谢途径为人参皂苷Rg_2→原人参三醇→脱氢原人参三醇;人参皂苷Re主要被代谢为4个产物,代谢途径为人参皂苷Re→人参皂苷Rg_2→人参皂苷F_1→原人参三醇→脱氢原人参三醇;人参皂苷Rd主要被代谢为4个产物,代谢途径为人参皂苷Rd→人参皂苷Rg_3和人参皂苷F_2→人参皂苷Rh_2→原人参二醇;人参皂苷Rb_1主要被代谢为5个产物,分别为人参皂苷Rb_1→人参皂苷Rd→人参皂苷Rg_3和人参皂苷F_2→人参皂苷Rh_2→原人参二醇。综上所述,6种皂苷类单体均能够被离体大鼠肠道菌群代谢,主要的代谢途径为脱糖基和脱氢。
To investigate the metabolism of six saponins by rat intestinal bacteria in vitro. Six saponins,including notoginsenoside R_1,ginsenoside Rg_1,ginsenoside Rg_2,ginsenoside Re,ginsenoside Rd and ginsenoside Rb_1,were incubated for 8 and 24 h with rat intestinal bacteria under anaerobic environment,respectively. After the samples were precipitated by acetonitrile and extracted with ethyl acetate,LC-Q-TOF-MS / MS was applied for the qualitative analysis of the metabolites. The potential metabolites in rat feces were analyzed by comparing the total ion current of the test samples and blank samples and analyzing the quasi-molecular ion and fragment ion of all chromatograms. The results showed that six saponins could be easily metabolized by rat intestinal bacteria. Notoginsenoside R_1 was mainly metabolized into five metabolites,and it' s metabolic pathway was notoginsenoside R_1→ginsenoside Rg_1→ginsenoside Rh_1 and ginsenoside F_1→protopanaxatriol→dehydrogenated protopanaxatriol. Ginsenoside Rg_1 was mainly metabolized into four metabolites,and it's metabolic pathway was ginsenoside Rg_1→ginsenoside Rh_1 and ginsenoside F_1→protopanaxatriol→dehydrogenated protopanaxatriol. Ginsenoside Rg_2 was mainly metabolized into two metabolites,and it' s metabolic pathway was ginsenoside Rg_2→ protopanaxatriol→dehydrogenated protopanaxatriol. Ginsenoside Re was mainly metabolized into four metabolites,and it' s metabolic pathway was ginsenoside Re→ginsenoside Rg_2→ginsenoside F_1→protopanaxatriol→dehydrogenated protopanaxatriol. Ginsenoside Rd was mainly metabolized into four metabolites,and it's metabolic pathway was ginsenoside Rd→ginsenoside Rg_3 and ginsenoside F_2→ginsenoside Rh_2→protopanaxadiol. Ginsenoside Rb_1 was mainly metabolized into five metabolites,and it's metabolic pathway was ginsenoside Rb_1→ginsenoside Rd→ginsenoside Rg_3 and ginsenoside F_2→ginsenoside Rh_2→protopanaxadiol. In summary,six saponins could be quickly metabolized by rat intestinal bacteria in vitro. Their major metabolic pathways were deglycosylation and dehydrogenation.

关键词(KeyWords): 大鼠肠道菌群;皂苷类成分;LC-Q-TOF-MS/MS;代谢;脱糖基
rat intestinal bacteria;saponins;LC-Q-TOF-MS/MS;metabolism;deglycosylation

Abstract:

Keywords:

基金项目(Foundation): 国家“重大新药创制”科技重大专项(2013ZX09402203)

作者(Author): 高霞;耿婷;马阳;李艳静;黄文哲;王振中;萧伟;
GAO Xia;GENG Ting;MA Yang;LI Yan-jing;HUANG Wen-zhe;WANG Zhen-zhong;XIAO Wei;Jiangsu Kanion Pharmaceutical Co.,Ltd.;State Key Laboratory of Pharmaceutical New-tech for Chinese Medicine;

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