Comparisons of the bioavailability of icariin, icariside II, and epimedin C in rats after oral administration of total flavonoids of Epimedium brevicornu Maxim. and its three formulations.

Abstract

The low bioavailability of insoluble flavonoids in the total flavonoids of Epimedium brevicornu Maxim. (TFE) severely hindered its clinical efficacy exertion. This research attempted to evaluate the promoting effects of pharmaceutical strategies, including nanosuspensions (NS), cyclodextrin inclusion complexes (CD), and solid dispersions (SD), on the oral absorption of active components in TFE. A rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to quantify ten pentenyl flavonoids of TFE in rat plasma. Good linearity was presented within the expected ranges (0.1 ∼ 10 ng/mL) in the calibration curves for ten analytes with an acceptable intra- and inter-day precision and accuracy of < 11.34 % and ± 11.91 %, respectively. By employing this selective UPLC-MS/MS method, the full-scale concentration-time curve for icariin (ICA), icariin II (ICA II), and epimedin C (EPI C) were drawn after oral administration of the crude TFE and its formulations. The results showed that the relative bioavailability (F_rel) of ICA and ICA II in the NS and CD formulations were 228-295 % when the crude TFE was as a reference, whereas the F_rel of ICA, ICA II, and EPI C in SD formulation were 416 %, 234 %, and 112 %, respectively. The findings suggest that SD technology holds significant promise for enhancing the oral bioavailability of various poorly soluble ingredients in herbal extracts, such as TFE, and for augmenting their therapeutic capabilities in clinical practice.