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. 2016 Aug 31;21(9):1158.
doi: 10.3390/molecules21091158.

Icariin Metabolism by Human Intestinal Microflora

Hailong Wu  1 , Mihyang Kim  2 , Jaehong Han  3
Affiliations

Icariin Metabolism by Human Intestinal Microflora

Hailong Wu et al. Molecules. .

Abstract

Icariin is a major bioactive compound of Epimedii Herba, a traditional oriental medicine exhibiting anti-cancer, anti-inflammatory and anti-osteoporosis activities. Recently, the estrogenic activities of icariin drew significant attention, but the published scientific data seemed not to be so consistent. To provide fundamental information for the study of the icaritin metabolism, the biotransformation of icariin by the human intestinal bacteria is reported for the first time. Together with human intestinal microflora, the three bacteria Streptococcus sp. MRG-ICA-B, Enterococcus sp. MRG-ICA-E, and Blautia sp. MRG-PMF-1 isolated from human intestine were reacted with icariin under anaerobic conditions. The metabolites including icariside II, icaritin, and desmethylicaritin, but not icariside I, were produced. The MRG-ICA-B and E strains hydrolyzed only the glucose moiety of icariin, and icariside II was the only metabolite. However, the MRG-PMF-1 strain metabolized icariin further to desmethylicaritin via icariside II and icaritin. From the results, along with the icariin metabolism by human microflora, it was evident that most icariin is quickly transformed to icariside II before absorption in the human intestine. We propose the pharmacokinetics of icariin should focus on metabolites such as icariside II, icaritin and desmethylicaritin to explain the discrepancy between the in vitro bioassay and pharmacological effects.

Keywords: Epimedium koreanum; biotransformation; desmethylicaritin; human intestinal bacteria; icariin; icariside II; icaritin.

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Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Molecular structures of the major prenylflavonoids isolated from Epimedii Herba.
Figure 2
Figure 2
HPLC chromatograms of icariin biotransformation products. Each chromatogram was obtained from the different human intestinal microflora. Microflora a, b and c showed icariside II, icaritin and desmethylicaritin formation, respectively, after 48 h.
Figure 3
Figure 3
MS spectra of icariin and its metabolites. Thermo Fisher Scientific LCQ fleet instrument (Thermo Scientific, Waltham, MA, USA) was used for electrospray ionization mass spectrometry (ESI-MS) analysis. ESI condition: spray voltage, 5.4 kV; sheath gas, 15 arbitrary units; auxiliary gas, five arbitrary units; heated capillary temperature, 275 °C; capillary voltage, 27 V; and tube lens, 100 V.
Figure 3
Figure 3
MS spectra of icariin and its metabolites. Thermo Fisher Scientific LCQ fleet instrument (Thermo Scientific, Waltham, MA, USA) was used for electrospray ionization mass spectrometry (ESI-MS) analysis. ESI condition: spray voltage, 5.4 kV; sheath gas, 15 arbitrary units; auxiliary gas, five arbitrary units; heated capillary temperature, 275 °C; capillary voltage, 27 V; and tube lens, 100 V.
Figure 4
Figure 4
HPLC chromatogram changes at 270 nm absorption over icariin metabolism by Blautia sp. MRG-PMF1.
Figure 5
Figure 5
Time-dependent biotransformation of icariin by (a) Streptococcus sp. MRG-ICA-B and (b) Blautia sp. MRG-PMF-1.
Figure 6
Figure 6
Proposed metabolic pathway of icariin in human intestine.
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