Effect of Eclipta prostrata on 11Beta-Hydroxysteroid Dehydrogenase in Rat Liver and Kidney.

Chenshu Xu,Bin Ren,Binghua Wei,Xiaohua Fu,Meijuan Luo,Ruiming Li,Lei Tang,Shidai Liu

doi:10.1155/2014/651053

Abstract

Eclipta prostrata (EP) is often prescribed in combination with glucocorticoid to treat glomerular nephritis, nephrotic syndrome, and IgA nephropathy in clinical practice of Traditional Chinese Medicine. Previous studies from our laboratory revealed that coadministration of EP significantly increased the plasma concentration of prednisolone while decreased the level of cotreated prednisone in rats. However, the underlying mechanism remains unclear. 11β-Hydroxysteroid dehydrogenase (11β-HSD) belongs to the family of oxidoreductases that catalyze the interconversion of prednisone to active prednisolone. Therefore, the current study aimed to investigate the effects of EP on the activity and expression of 11β-HSD in rat liver and kidney. The results showed that oral administration of EP significantly increased the activity of 11β-HSD I in the liver and 11β-HSD II in the kidney by employing the microsomal incubation system. Moreover, gene and protein expressions of 11β-HSD I and 11β-HSD II were also increased in rat liver and kidney, respectively. These results suggest that the effects of EP on 11β-HSD may attribute to the mechanism that administration of EP improves the efficacy and reduces adverse drug reactions of glucocorticoid in patients undergoing combinational therapy.

Highlights

Glucocorticoids are a class of steroid hormones that cause immunological and metabolic effects by binding to the glucocorticoid receptor
11β-Hydroxysteroid dehydrogenase (11β-HSD) belongs to the family of oxidoreductases that regulates the access of glucocorticoids to the steroid receptors [2]. 11β-HSD catalyzes the interconversion of physiologic glucocorticoids such as cortisol to its inactive metabolite cortisone, as well as prednisone to active prednisolone
There are two distinct 11β-HSD enzymes. 11β-HSD I is expressed at high levels in the liver, where orally administered prednisone is primarily activated and extensively converted to prednisolone, the active counterpart of prednisone through first-pass metabolism [4, 5]. 11β-HSD II, is a powerful inactivator of glucocorticoid and expressed primarily in the kidney, which is the principle site for generating inactive prednisone [6]

Summary

Introduction

Glucocorticoids are a class of steroid hormones that cause immunological and metabolic effects by binding to the glucocorticoid receptor. Prednisone can be rapidly converted to prednisolone, its active 11β-hydroxyl metabolite, by 11β-hydroxysteroid dehydrogenase I (11β-HSD I) [1]. 11β-Hydroxysteroid dehydrogenase (11β-HSD) belongs to the family of oxidoreductases that regulates the access of glucocorticoids to the steroid receptors [2]. 11β-HSD catalyzes the interconversion of physiologic glucocorticoids such as cortisol to its inactive metabolite cortisone, as well as prednisone to active prednisolone. 11β-HSD I is expressed at high levels in the liver, where orally administered prednisone is primarily activated and extensively converted to prednisolone, the active counterpart of prednisone through first-pass metabolism [4, 5]. 11β-HSD II, is a powerful inactivator of glucocorticoid and expressed primarily in the kidney, which is the principle site for generating inactive prednisone [6]. Regulation of tissue concentration of glucocorticoid by 11βHSD has been shown to involve in several diseases, such

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