Original article| Volume 132, ISSUE 1, P32-38, July 1998

Inhibition of 11β-hydroxysteroid dehydrogenase by bioflavonoids and their interaction with furosemide and gossypol

  • Junhua Guo
    Departments of Pharmacology and Medicine, Cornell University Medical College, New York, New York, USA
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  • Marcus M. Reidenberg
    Reprint requests: Marcus M. Reidenberg, MD, Department of Pharmacology, Cornell University Medical College, 1300 York Avenue, New York, NY 10021.
    Departments of Pharmacology and Medicine, Cornell University Medical College, New York, New York, USA
    Search for articles by this author
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      Inhibition of 11β-hydroxysteroid dehydrogenase (11β-OHSD) can cause a mineralocorticoid effect. This enzyme, in guinea pig renal cortex microsomes in vitro, is inhibited by quercetin, tea polyphenols, furosemide, and gossypol. The dietary polyphenols, quercetin and tea polyphenols, interact with furosemide to enhance its 11β-OHSD inhibitory effect. Tea polyphenols added to the effect of gossypol. We conclude that the diet contains inhibitors of 11β-OHSD that can alter the activity of this enzyme and may modify the degree of endogenous mineralocorticoid activity.


      11β-OHSD (11β-Hydroxysteroid dehydrogenase), CI (combination index), IC50 (median inhibitory concentration), NAD (nicotinamide adenine dinucleotide), NADP (nicotinamide adenine dinucleotide phosphate)
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        • Wilson RC
        • Harbison MD
        • Krozowski ZS
        • et al.
        Several homozygous mutations in the gene for 11β-Hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess.
        J Clin Endocrinol Metab. 1995; 80: 3145-3150
      1. Frey F Funder J Monder C First symposium on 11β-hydroxysteroid dehydrogenase. 2nd ed. Steroids. 59. 1994: 61-172
        • Stewart PM
        • Krozowski ZS
        • Gupta A
        • et al.
        Hypertension in the syndrome of apparent mineralocorticoid excess due to mutation of the 11β-hydroxysteroid dehydrogenase type 2 gene.
        Lancet. 1996; 347: 88-91
        • Sang GW
        • Lorenzo NJ
        • Reidenberg MM
        Inhibitory effects of gossypol on corticosteroid 11β-hydroxysteroid dehydrogenase from guinea pig kidney: A possible mechanism for causing hypokalemia.
        J Steroid Biochem. 1991; 39: 169-176
        • Song D
        • Lorenzo BJ
        • Reidenberg MM
        Inhibition of 11β-Hydroxysteroid dehydrogenase by gossypol and bioflavonoids.
        J Lab Clin Med. 1992; 120: 792-797
        • Zhang Y-D
        • Lorenzo B
        • Reidenberg MM
        Inhibition of 11β-Hydroxysteroid dehydrogenase obtained from guinea pig kidney by furosemide, naringenin and some other compounds.
        J Steroid Biochem. 1994; 49: 81-85
        • Lee YS
        • Lorenzo BJ
        • Koufis T
        • Reidenberg MM
        Grapefruit juice and its flavonoids inhibit 11β-hydroxysteroid dehydrogenase.
        Clin Pharmacol Ther. 1996; 59: 62-71
        • Asbury MJ
        • Gatenby PBB
        • O'Sullivan S
        • Bourke E
        Bumetanide: Potent new “loop” diuretic.
        Br Med J. 1972; 1: 211-213
        • Ramsay LE
        • McInnes GI
        • Hettiarachchi J
        • Shelton J
        • Scott P
        Bumetanide and furosemide: A comparison of dose-response curves in healthy men.
        Br J Clin Pharmacol. 1978; 5: 243-247
        • Brater DC
        • Fox BS
        • Chennavasin P
        Electrolyte excretion patterns, intravenous and oral doses of bumetanide compared to furosemide.
        J Clin Pharmacol. 1981; 21: 599-603
        • Qian SZ
        • Wang Z-G
        Gossypol: A potential antifertility agent for males.
        Ann Rev Pharmacol Toxicol. 1984; 24: 329-360
        • Ho CT
        • Chen Q
        • Shi H
        • Zhang KQ
        • Rosen RT
        Antioxidative effect of polyphenol extract prepared from various Chinese teas.
        Prev Med. 1992; 21: 520-525
        • Chou J
        • Chou TC
        Dose-effect analysis with microcomputer: Quantitation of ED50, LD50, synergism, antagonism, low-dose risk, receptor-ligand binding and enzyme kinetics.
        ([manual and software]) Biosoft, Cambridge, UK1987
        • Chou TC
        • Talalay P
        Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors.
        Adv Enzyme Regul. 1989; 22: 27-55
        • Chou TC
        The median-effect principle and the combination index for quantitation of synergism and antagonism.
        in: Chou TC Rideout D Synergism and antagonism in chemotherapy. Academic Press, San Diego1991: 61-102
        • Berenbaum MC
        Synergy, additivism, and antagonsim in immunosuppression.
        Clin Exp Immunol. 1977; 28: 1-18
        • Borst JGG
        • ten Holt SP
        • de Vries LA
        • Molhuysen JA
        Synergistic action of liquorice and cortisone in Addison's and Simmonds's disease.
        Lancet. 1953; 1: 657-661
        • Stewart PM
        • Wallace AM
        • Valentino R
        • Burt D
        • Shackleton CHL
        • Edwards CRW
        Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age.
        Lancet. 1987; 21: 821-824
        • MacKenzie MA
        • Hoefnagels WHL
        • Jansen RWMM
        • Benraad TJ
        • Kopenborg PWC
        The influence of glycyrrhetinic acid on plasma cortisol and cortisone in healthy young volunteers.
        J Clin Endocrinol Metab. 1990; 70: 1637-1641
        • Buhler H
        • Perschel FH
        • Hierholzer K
        Inhibition of rat renal 11β-Hydroxysteroid dehydrogenase by steroidal compounds and triterpenoids: Structure/function relationship.
        Biochem Biophys Acta. 1991; 1075: 206-212
        • Latif SA
        • Hartman LR
        • Souness GW
        • Morris DJ
        Possible endogenous regulators of steroid inactivating enzymes and glucocorticoid-induced Na+ retention.
        Steroids. 1994; 59: 352-356
        • Perschel FH
        • Buhler H
        • Hierholzer K
        Bile acids and their amidates inhibit 11β-Hydroxysteroid dehydrogenase obtained from rat kidney.
        Pflugers Arch (Eur J Physiol). 1991; 418: 538-543
        • Bernal AL
        • Flint APF
        • Anderson ABM
        • Turnbull AC
        11β-Hydroxysteroid dehydrogenase activity (E. C. 1. 1. 1. 146) in human placenta and decidua.
        J Steroid Biochem. 1980; 13: 1081-1087
        • Morris DJ
        • Semafuko WEB
        • Latif SA
        • Vogel B
        • Grimes CA
        • Sheff MF
        Detection of glycyrrhetinic acid-like factors (GALFs) in human urine.
        Hypertension. 1992; 20: 356-360
      2. Lee LS, Reidenberg MM. A method for measuring naringenin in biological fluids and its disposition from grapefruit juice by man. Pharmacology. In press.

        • Gao YT
        • McLaughlin JK
        • Blot WJ
        • Dai Q
        • Fraumeni Jr, JF
        Reduced risk of esophageal cancer associated with green tea consumption.
        J Natl Cancer Inst. 1994; 86: 855-858
        • Pierpoint WS
        Flavonoids in the human diet.
        in: Cody C Middleton Jr, E Harborne JB Plant flavonoids in the human diet. Alan R Liss, New York1996: 125-190
        • Edwards DJ
        • Bellvue III, FH
        • Woster PM
        Identification of 6′,7′-dihydroxybeigamottin, a cytochrome P450 inhibitor in grapefruit juice.
        Drug Metab Dispos. 1996; 24: 1287-1290
        • Reidenberg MD
        • Gu Z-P
        • Lorenzo B
        • et al.
        Differences in serum potassium concentrations in normal men in different geographic locations.
        Clin Chem. 1993; 39: 72-75
        • Gu Z-P
        • Segal S
        • Reidenberg MM
        Serum potassium: Values in normal men in Shanghai vs those in men from Shanghai living abroad.
        Clin Chem. 1994; 40: 340