Intestinal Absorption and Presystemic Elimination of Various Chemical Constituents Present in GBE50 Extract, a Standardized Extract of Ginkgo biloba Leaves

The nature and level of systemic exposure to active herbal constituents will profoundly affect their bioactivities at action sites, which is fundamental in understanding their roles in the overall beneficial effects of an herbal medicine. The objective of this study is to gain a full picture of the systemic exposure to various putatively active ginkgo constituents after p.o. administration of GBE50 extract, a standardized extract of Ginkgo biloba leaves, to rats and understanding of the relevant mechanisms governing the intestinal absorption and presystemic elimination. To define the ginkgo compounds to be studied, a literature informatics-guided chemical profiling revealed that GBE50 extract contained 71 ginkgo constituents, including terpene lactones, flavonols, flavones, an isoflavone, biflavones, flavanols, and carboxylic acids, at levels ranging from 0.01 to 55.3mg/g. Among the ginkgo constituent groups the terpene lactones and the flavonol glycosides were significantly measurable in the post-administrative rat plasma. The intestinal absorption of terpene lactones appeared to be dictated by their intermediate membrane permeability, while the influences of MDR-1-mediated intestinal efflux and the presystemic metabolism and biliary excretion might be limited. Because of their deglycosylation, their absence in the small intestine and relatively slow presystemic elimination, many intact flavonol glycosides could be absorbed albeit to a limited extent. Colonic deglycosylation of the flavonol glycosides occurred and the glucuronides of flavonol aglycones were also measured in the rat plasma. Although some biflavones had relatively high abundance in GBE50 extract, these ginkgo constituents were not measured in the rat plasma because of their poor solubility and poor permeability that hindered the intestinal absorption. The levels of the remaining ginkgo constituents in GBE50 extract were too low to be measured in the rat plasma. The current study enabled us to better understand the nature of systemic exposure to ginkgo compounds after p.o. administration of GBE50 extract and to more precisely implement multi-component PK study of the extract.