Magnolol from Magnolia officinalis inhibits 11β-hydroxysteroid dehydrogenase without increases of corticosterone and thymocyte apoptosis in mice

Magnolol is an 11 beta -hydroxysteroid dehydrogenase (11 beta -HSD) inhibitor contained in Magnolia officinalis which is used in Chinese remedies. We have reported that glycyrrhetinic acid, a strong 11 beta -HSD inhibitor isolated from licorice, induces apoptosis of murine thymocytes via accumulation of corticosterone. In this paper, we report that magnolol inhibited 11 beta -HSD without increases in the blood concentration of corticosterone and in thymocyte apoptosis in mice. Oxidative activities of the enzyme (from corticosterone to Il-dehydrocorticosterone) in liver, kidney and thymus in vitro were examined 24 h after a single administration of magnolol. Magnolol inhibited the enzyme activity in kidney (P < 0.0001) and thymus (P < 0.002), while the activity in liver was not affected. Blood concentrations of corticosterone in the magnolol-treated mice were unexpectedly lower than those in the control animals (P < 0.002). This means that the inhibition of 11<beta>-HSD by magnolol did not increase the systemic level of corticosterone which is relevant to thymocyte apoptosis. Accordingly, our flow cytometric analysis of thymocytes after magnolol treatment showed no change in the number of apoptotic cells. We concluded that unlike glycyrrhetinic acid, magnolol selectively inhibited 11 beta -HSD in kidney and thymus but not in liver, so that the blood concentrations of corticosterone could not exceed the control level.