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Review
. 2019 Oct 14;24(20):3693.
doi: 10.3390/molecules24203693.

Metabolism, Transport and Drug-Drug Interactions of Silymarin

Ying Xie  1 , Dingqi Zhang  2 , Jin Zhang  3 , Jialu Yuan  4
Affiliations
Review

Metabolism, Transport and Drug-Drug Interactions of Silymarin

Ying Xie et al. Molecules. .

Abstract

Silymarin, the extract of milk thistle, and its major active flavonolignan silybin, are common products widely used in the phytotherapy of liver diseases. They also have promising effects in protecting the pancreas, kidney, myocardium, and the central nervous system. However, inconsistent results are noted in the different clinical studies due to the low bioavailability of silymarin. Extensive studies were conducted to explore the metabolism and transport of silymarin/silybin as well as the impact of its consumption on the pharmacokinetics of other clinical drugs. Here, we aimed to summarize and highlight the current knowledge of the metabolism and transport of silymarin. It was concluded that the major efflux transporters of silybin are multidrug resistance-associated protein (MRP2) and breast cancer resistance protein (BCRP) based on results from the transporter-overexpressing cell lines and MRP2-deficient (TR-) rats. Nevertheless, compounds that inhibit the efflux transporters MRP2 and BCRP can enhance the absorption and activity of silybin. Although silymarin does inhibit certain drug-metabolizing enzymes and drug transporters, such effects are unlikely to manifest in clinical settings. Overall, silymarin is a safe and well-tolerated phytomedicine.

Keywords: drug–drug interaction (DDI); efflux transporters; metabolism; silybin/silymarin.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Chemical structures of silybin diastereomers.
Figure 2
Figure 2
Transporters related to the disposition and elimination of silybin. BCRP: breast cancer resistance protein; MRP2: multidrug resistance-associated protein.
Figure 3
Figure 3
Metabolism of silybin and its major metabolites. UGT: UDP-glucuronosyltransferase; SULTs: sulfotransferases; CYP2C8: Cytochrome P450 2C8.
See this image and copyright information in PMC

References

    1. Bijak M. Silybin. a Major Bioactive Component of Milk Thistle (Silybum marianum L. Gaernt.)—Chemistry, Bioavailability, and Metabolism. Molecules. 2017;22:1942. doi: 10.3390/molecules22111942. - DOI - PMC - PubMed
    1. Rainone F. Milk thistle. Am. Fam. Physician. 2005;72:1285–1288. - PubMed
    1. Lee J.I., Narayan M., Barrett J.S. Analysis and comparison of active constituents in commercial standardized silymarin extracts by liquid chromatography-electrospray ionization mass spectrometry. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2007;845:95–103. doi: 10.1016/j.jchromb.2006.07.063. - DOI - PubMed
    1. Han Y.H., Lou H.X., Ren D.M., Sun L.R., Ma B., Ji M. Stereoselective metabolism of silybin diastereoisomers in the glucuronidation process. J. Pharm. Biomed. Anal. 2004;34:1071–1078. doi: 10.1016/j.jpba.2003.12.002. - DOI - PubMed
    1. Kim N.C., Graf T.N., Sparacino C.M., Wani M.C., Wall M.E. Complete isolation and characterization of silybins and isosilybins from milk thistle (Silybum marianum) Org. Biomol. Chem. 2003;1:1684–1689. doi: 10.1039/b300099k. - DOI - PubMed