Intestinal Absorption Mechanisms of Prenylated Flavonoids Present in the Heat-Processed Epimedium koreanum Nakai (Yin Yanghuo)

Abstract

Purpose-The purpose is to determine absorption mechanism of five bioactive prenylated flavonoids (baohuoside I, icariin, epimedine A, B, and C) present in heat-processed Epimedium koreanum Nakai (Yin Yanghuo).Methods-Transport of five prenylated flavonoids present in heat-processed herbs were studied in the human intestinal Caco-2 model and the perfused rat intestinal model.Results-In the perfused rat intestinal model, prenylated flavonoids with a monoglucosidic bond (e.g., icariin) was rapidly hydrolyzed into corresponding metabolites (e.g., baohuoside I). In the Caco-2 model, apical to basolateral permeability of a monoglycoside baohuoside I (1.46 ×10 −6 cm/ sec) was more than 2 folds greater than four prenylated flavonoids with 2 or more sugar moieties (<0.6×10 −6 cm/sec). The slow apical to basolateral transport of baohuoside I was the result of efflux. This efflux was carrier-mediated and active since its transport was vectorial, concentration-and temperature-dependent with activation energies greater than 15 kcal/mol. Efflux of baohuoside I was significantly suppressed by inhibitors of BCRP and MRP2, whereas efflux of icariin was significantly inhibited only by p-glycoprotein inhibitor verapamil. Because YHH is often heat-processed for better efficacy, we determined and found the optimal condition for increasing contents of more bioavailable flavonoids (i.e., baohuoside I) to be 160-170°C for 5-7 min.Conclusions-Poor bioavailability of prenylated flavonoids results from their poor intrinsic permeation and transporter-mediated efflux. Heat processing parameters may be optimized to preserve the herb's bioavailable flavonoids, which help retain and improve its efficacy during processing.

Optimization and anticancer activity in vitro and in vivo of baohuoside I incorporated into mixed micelles based on lecithin and Solutol HS 15

“…Moreover, baohuoside I possesses a low absorptive permeability and a high rate of efflux via apical efflux transporters such as multidrug resistance-associated proteins 1 and 2 (MRP 1 and MRP 2) and P-glycoprotein (P-gp). However, the membrane permeability of baohuoside I is slightly better than that of other flavonoids in H. epimedii, and the rate of efflux (P BA / P AB ) of baohuoside I reached 9.84 in a previous study using Caco-2 cells (Chen et al, 2008). These peculiarities restrict the application of baohuoside I in the management of cancer therapy.…”

Icariin regulates systemic iron metabolism by increasing hepatic hepcidin expression through Stat3 and Smad1/5/8 signaling

“…Experiments using mice confirmed the stimulatory effect of icariin on hepatic hepcidin. In addition, according to previous studies on natural Chinese medicinal herbs (50)(51)(52), the compounds similar to icariin would be rapidly eliminated with a short half-life if administered orally to animals. By contrast, these compounds revealed great bioavailability with a long half-life when administered intraperitoneally (53).…”

D-&alpha;-Tocopheryl polyethylene glycol succinate/Solutol HS 15 mixed micelles for the delivery of baohuoside I against non-small-cell lung cancer: optimization and in vitro, in vivo evaluation

“…When tumors reached an acceptable size, DiR-M was injected into the tail vein of the tumor-bearing mice at a dose of 5.0 mg/kg to investigate the in vivo distribution. The mice were anesthetized and imaged at predetermined time points (2,4,8,12, and 24 hours) after intravenous injection using the Maestro in vivo imaging system (NightOWL II LB983; Berthold Technologies, Bad Wildbad, Germany).…”

“…However, the membrane permeability of baohuoside I is slightly better than that of the other flavonoids in Herba epimedii, and the rate of efflux (P BA /P AB ) of baohuoside I reached 9.84 in a previous study using Caco-2 cells. 8 These peculiarities restrict the application of baohuoside I in the management of cancer therapy. Thus, poor aqueous solubility, low membrane permeability, and a severe efflux phenomenon all limit the therapeutic use of baohuoside I in humans.…”