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

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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.

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Authors and Affiliations

  1. Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 1441 Moursund Street, Houston, TX, 77030, USA

    Yan Chen & Ming Hu

  2. Jiangsu Provincial Academy of Chinese Medicine, 100 Hongshan Road, Nanjing, China, 210028

    Yan Chen, Yan Hong Zhao & Xiao Bin Jia

Authors
  1. Yan Chen
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  2. Yan Hong Zhao
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  3. Xiao Bin Jia
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  4. Ming Hu
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Corresponding authors

Correspondence to Xiao Bin Jia or Ming Hu.

Additional information

The work is supported by NIH GM 70737 to MH and National Natural Science Foundation of China (Grant No. 30572372) to YC, YHZ and XBJ. Y.C. was also supported by a training grant from Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu, China.

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Chen, Y., Zhao, Y.H., Jia, X.B. et al. Intestinal Absorption Mechanisms of Prenylated Flavonoids Present in the Heat-Processed Epimedium koreanum Nakai (Yin Yanghuo). Pharm Res 25, 2190–2199 (2008). https://doi.org/10.1007/s11095-008-9602-7

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  • DOI: https://doi.org/10.1007/s11095-008-9602-7

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