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Figure 1.

Physiological role of the two isoenzymes 11β-HSD type 1 and 2.

Predominant reaction direction of the NADP(H)-dependent enzyme 11β-HSD1 by catalyzing the conversion of inactive cortisone to receptor-active cortisol. The reverse reaction is mediated by the unidirectional NAD-dependent 11β-HSD type 2.

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Figure 1 Expand

Figure 2.

Inhibition of cortisone reduction by three different types of tea (Green, Black and White Tea) in human liver microsomes.

Product yields were quantified by integration of cortisol peaks. The product yields of the controls without any type of tea were normalized to 100% enzyme activity and the residual activity expressed as percent of the control. Bars represent the mean ±SD of at least three repeat experiments.

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Figure 3.

Dose-dependent inhibition of cortisone reduction by green tea in human liver microsomes. Results are presented as means ±SD (n = 4).

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Figure 4.

Inhibitory effects of five tea catechins on cortisone reduction in human liver microsomes.

Bars represent the mean ±SD of at least three repeat experiments.

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Figure 5.

Chemical structures of five green tea catechins used in this study.

EGCG, (−)-epigallocatechin-3-gallate; EGC, (−)-epigallocatechin; EC, (−)-epicatechin; GC, (−)-gallocatechin; C, (−)-catechin.

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Figure 6.

Dose-dependent inhibition of cortisone reduction by EGCG in human liver microsomes.

Results are presented as means ±SD (n = 4).

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Figure 7.

Dose-dependent inhibition of cortisol oxidation by EGCG in human liver microsomes.

Results are presented as means ±SD (n = 4).

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Figure 8.

Dixon plot to characterize the inhibition type and to determine the Ki of EGCG on cortisone reduction in human liver microsomes.

The inset shows direct plotting of the same data.

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Figure 9.

Dixon plot to characterize the inhibition type and to determine the Ki of EGCG on cortisone reduction by purified 11β-HSD1.

The inset shows direct plotting of the same data.

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Figure 9 Expand

Table 1.

Inhibition constants of EGCG on cortisone reduction with human liver microsomes and purified human 11β-HSD1.

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Figure 10.

Western Blot analysis of EGCG treated and EGCG untreated purified human liver 11β-HSD1.

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Figure 11.

Binding model of EGCG docked to the active site of human 11β-HSD1.

Shown is a binary complex of 11β-HSD1 (PDB: 2RBE) with EGCG (blue) and NADPH (green). K187 belongs to the catalytic triade (yellow) and forms a predicted hydrogen bond with EGCG (distance: 2.1 Å).

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