Abstract
Epimedium spp. is commonly used in Traditional Chinese Medicine. Epimedins A, B, and C are three major bioactive flavonoids found in Epimedium spp. that share similar chemical structures. In this study, the intestinal absorption mechanism of these three compounds was investigated using the Caco-2 cell monolayer model in both the apical-to-basolateral (A-B) and the basolateral-to-apical (B-A) direction. The absorption permeability (PAB) of epimedins A, B, and C were extremely low and increased as the concentration of the epimedins increased from 5 to 20 μM, but, at 40 μM, the PAB values were reduced. Meanwhile, the amount of transported compounds increased in a time-dependent manner. The PAB of epimedins A and C were significantly increased and efflux ratios decreased in the presence of verapamil (an inhibitor of P-glycoprotein) and dipyridamole (an inhibitor of breast cancer resistance protein) while, in the presence of MK571 (an inhibitor of multidrug resistance proteins), the absorption of epimedins A and C did not change significantly, indicating that P-gp and BCRP might be involved in the transport of epimedins A and C. The PAB of epimedin B significantly increased while its secretory permeability (PBA) significantly decreased in the presence of dipyridamole, indicating that BCRP might be involved in the transport of epimedin B. No obvious changes in the transport of epimedin B were observed in the presence of verapamil and MK571. In summary, our results clearly demonstrate, for the first time, that poor bioavailability of these three prenylated flavonoids is the result of poor intrinsic permeability and efflux by apical efflux transporters.
Highlights
For over 2,000 years, Epimedium spp. has been widely used in China as an important medicinal herb [1]
In order to determine which concentration of epimedins A, B, and C can be used in transport experiments, the in vitro cytotoxicity of the above compounds was analyzed by cell viability experiment
The results demonstrated that verapamil and dipyridamole significantly increased the absorptive permeability, but decreased the secretory permeability of epimedin C (Figure 4c)
Summary
For over 2,000 years, Epimedium spp. has been widely used in China as an important medicinal herb [1]. The main active constituents of the herb are prenylated flavonoids, among which icariin, baohuoside I, and epimedins A, B, and C are the most important (Figure 1) [6,7,8]. These flavonoids show good pharmacological actions, their bioavailability is poor. The aim of present study was to further investigate the intestinal absorptive characteristics of epimedins A, B, and C by using the same Caco-2 cell model we used earlier. P-gp, MRPs, and BCRP in the transport of epimedins A, B, and C were determined
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