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Isoflavones: estrogenic activity, biological effect and bioavailability

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Abstract

Isoflavones are phytoestrogens with potent estrogenic activity; genistein, daidzein and glycitein are the most active isoflavones found in soy beans. Phytoestrogens have similarity in structure with the human female hormone 17-β-estradiol, which can bind to both alpha and beta estrogen receptors, and mimic the action of estrogens on target organs, thereby exerting many health benefits when used in some hormone-dependent diseases. Numerous clinical studies claim benefits of genistein and daidzein in chemoprevention of breast and prostate cancer, cardiovascular disease and osteoporosis as well as in relieving postmenopausal symptoms. The ability of isoflavones to prevent cancer and other chronic diseases largely depends on pharmacokinetic properties of these compounds, in particular absorption and distribution to the target tissue. The chemical form in which isoflavones occur is important because it influences their bioavailability and, therefore, their biological activity. Glucose-conjugated isoflavones are highly polar, water-soluble compounds. They are hardly absorbed by the intestinal epithelium and have weaker biological activities than the corresponding aglycone. Different microbial families of colon can transform glycosylated isoflavones into aglycones. Clinical studies show important differences between the aglycone and conjugated forms of genistein and daidzein. The evaluation of isoflavone metabolism and bioavailability is crucial to understanding their biological effects. Lipid-based formulations such as drug incorporation into oils, emulsions and self-microemulsifying formulations have been introduced to increase bioavailability. Complexation with cyclodextrin also represent a valid method to improve the physicochemical characteristics of these substances in order to be absorbed and distributed to target tissues. We review and discuss pharmacokinetic issues that critically influence the biological activity of isoflavones.

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Abbreviations

ER:

Estrogen receptors

HRT:

Hormone replacement therapy

AUC:

Area under the plasma concentration curve

T max :

Time to maximum concentration

IFG:

Isoflavone glucoside

TVP:

Textured vegetable protein

C max :

Maximum plasma concentration

t 1/2 :

Plasma concentration half-life

AUC0−t :

Area under the plasma concentration curve administration to last observed concentration at time t

SMEDDS:

Self-microemulsifying drug delivery system

IFE:

Isoflavone extract

CD:

Cyclodextrins

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Authors and Affiliations

  1. Pharmacokinetic Unit, Unifarm Research Center, Catania, Italy

    Daniela Cristina Vitale, Cateno Piazza, Barbara Melilli & Filippo Drago

  2. Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, Catania University, Viale A. Doria 6, 95125, Catania, Italy

    Filippo Drago & Salvatore Salomone

Authors
  1. Daniela Cristina Vitale
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  2. Cateno Piazza
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  3. Barbara Melilli
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  4. Filippo Drago
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  5. Salvatore Salomone
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Correspondence to Salvatore Salomone.

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Vitale, D.C., Piazza, C., Melilli, B. et al. Isoflavones: estrogenic activity, biological effect and bioavailability. Eur J Drug Metab Pharmacokinet 38, 15–25 (2013). https://doi.org/10.1007/s13318-012-0112-y

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  • DOI: https://doi.org/10.1007/s13318-012-0112-y

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