Lei Zhang1, Xiao-Yan Liu1, Wei Xu1, Xiu-Wei Yang2. 1. State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. 2. State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: xwyang@bjmu.edu.cn.
Abstract
BACKGROUND: Ginsenosides were considered as the main bioactive constituents in Ginseng Radix et Rhizoma (GRR). However, because of high polarity, ginsenosides were hard to be absorbed in human or animal gastrointestinal tract after oral administration. Up to now, very few studies have been performed in the area of simultaneous pharmacokinetic analysis of multiple ginsenosides with similar structures. PURPOSE: This research aimed to compare the different absorption characteristics of ginsenosides and aglycones between GRR and Baoyuan decoction (BYD), one of formulas containing GRR, with the same dosage. METHODS: GRR and BYD extracts were prepared with same method. A single dose of GRR and BYD extracts were administrated to rats through gavage, respectively. A solid phase extraction method was used to purify the plasma samples. An ultra-fast liquid chromatography coupled with tandem mass spectrometry (UFLC-MS/MS) method was established and fully validated for quantitative analysis. In addition, an in vitro incubation of GRR extract with intestinal flora was conducted to confirm the influence of gut microbiota to the absorption of ginsenosides and aglycones. RESULTS: The results of incubation experiments showed that most high polar ginsenosides could transform to less polar ginsenosides via intestinal flora. The validated UFLC-MS/MS method was sensitive and precise to simultaneously analyze the pharmacokinetics of multiple ginsenosides. After oral administration of GRR and BYD extracts, the pharmacokinetic results showed that a total of 11 ginsenosides and 2 aglycones could be quantitatively determined in both groups of plasma. Besides, five compounds were only quantified in BYD extract group. In addition, another 21 ginsenosides could be qualitatively measured. CONCLUSION: The results indicated significant pharmacokinetic differences of ginsenosides and aglycones between two groups. For most less polar ginsenosides who had better bioactivity, the preparation was possessed of higher plasma concentrations. The comparative results indicated that some co-existing compounds in BYD might inhibit the exocytosis of ginsenosides. Moreover, what is worth mentioning, some ginsenosides and aglycones could only be detected and quantified a few hours later after administration to rats. Combining with the in vitro incubation experiments, the results demonstrated that transformation of ginsenosides in gastrointestinal tract via intestinal flora existed during absorption.
BACKGROUND:Ginsenosides were considered as the main bioactive constituents in Ginseng Radix et Rhizoma (GRR). However, because of high polarity, ginsenosides were hard to be absorbed in human or animal gastrointestinal tract after oral administration. Up to now, very few studies have been performed in the area of simultaneous pharmacokinetic analysis of multiple ginsenosides with similar structures. PURPOSE: This research aimed to compare the different absorption characteristics of ginsenosides and aglycones between GRR and Baoyuan decoction (BYD), one of formulas containing GRR, with the same dosage. METHODS: GRR and BYD extracts were prepared with same method. A single dose of GRR and BYD extracts were administrated to rats through gavage, respectively. A solid phase extraction method was used to purify the plasma samples. An ultra-fast liquid chromatography coupled with tandem mass spectrometry (UFLC-MS/MS) method was established and fully validated for quantitative analysis. In addition, an in vitro incubation of GRR extract with intestinal flora was conducted to confirm the influence of gut microbiota to the absorption of ginsenosides and aglycones. RESULTS: The results of incubation experiments showed that most high polar ginsenosides could transform to less polar ginsenosides via intestinal flora. The validated UFLC-MS/MS method was sensitive and precise to simultaneously analyze the pharmacokinetics of multiple ginsenosides. After oral administration of GRR and BYD extracts, the pharmacokinetic results showed that a total of 11 ginsenosides and 2 aglycones could be quantitatively determined in both groups of plasma. Besides, five compounds were only quantified in BYD extract group. In addition, another 21 ginsenosides could be qualitatively measured. CONCLUSION: The results indicated significant pharmacokinetic differences of ginsenosides and aglycones between two groups. For most less polar ginsenosides who had better bioactivity, the preparation was possessed of higher plasma concentrations. The comparative results indicated that some co-existing compounds in BYD might inhibit the exocytosis of ginsenosides. Moreover, what is worth mentioning, some ginsenosides and aglycones could only be detected and quantified a few hours later after administration to rats. Combining with the in vitro incubation experiments, the results demonstrated that transformation of ginsenosides in gastrointestinal tract via intestinal flora existed during absorption.