Piper sarmentosum Effects on 11β-Hydroxysteroid Dehydrogenase Type 1 Enzyme in Serum and Bone in Rat Model of Glucocorticoid-Induced Osteoporosis.

Siti Mohamad Asri,Elvy Mohd Ramli,Ima Soelaiman,Farihah Suhaimi,Abdul Abdul Rashid,Muhamad Mat Noh

doi:10.3390/molecules21111523

Abstract

Glucocorticoid-induced osteoporosis is one of the common causes of secondary osteoporosis. Piper sarmentosum (Ps) extract possesses antioxidant and anti-inflammatory activities. In this study, we determined the correlation between the effects of Ps leaf water extract with the regulation of 11β-hydroxysteroid dehydrogenase (HSD) type 1 enzyme activity in serum and bone of glucocorticoid-induced osteoporotic rats. Twenty-four Sprague-Dawley rats were grouped into following: G1: sham-operated group administered with intramuscular vehicle olive oil and vehicle normal saline orally; G2: adrenalectomized (adrx) control group given intramuscular dexamethasone (120 μg/kg/day) and vehicle normal saline orally; G3: adrx group given intramuscular dexamethasone (120 μg/kg/day) and water extract of Piper sarmentosum (125 mg/kg/day) orally. After two months, the femur and serum were taken for ELISA analysis. Results showed that Ps leaf water extract significantly reduced the femur corticosterone concentration (p < 0.05). This suggests that Ps leaf water extract was able to prevent bone loss due to long-term glucocorticoid therapy by acting locally on the bone cells by increasing the dehydrogenase action of 11β-HSD type 1. Thus, Ps may have the potential to be used as an alternative medicine against osteoporosis and osteoporotic fracture in patients on long-term glucocorticoid treatment.

Highlights

Long-term glucocorticoid therapy induces osteoporosis and has become the most common cause of secondary osteoporosis
Molecules 2016, 21, 1523 of 11β-hydroxysteroid dehydrogenase (HSD) catalyze the interconversion of hormonally-active cortisol in humans to inactive cortisone in humans (11-dehydrocorticosterone in rodents) [5]. 11β-HSD type 1 is a low-affinity nicotinamide adenine dinucleotide phosphate (NADPH)-dependent bidirectional enzyme that can interconvert inactive cortisone to active cortisol, predominantly as a reductase enzyme
The endogenous glucocorticoids were replaced by dexamethasone to ensure a constant level of glucocorticoid in the rat

Summary

Introduction

Long-term glucocorticoid therapy induces osteoporosis and has become the most common cause of secondary osteoporosis. 11β-hydroxysteroid dehydrogenase (11β-HSD) isoenzymes play an important role in the regulation of corticosteroid hormonal action. Due to their pre-receptor action [4], the two isoenzymes. Molecules 2016, 21, 1523 of 11β-HSD catalyze the interconversion of hormonally-active cortisol in humans (corticosterone in rodents) to inactive cortisone in humans (11-dehydrocorticosterone in rodents) [5]. 11β-HSD type 1 is a low-affinity nicotinamide adenine dinucleotide phosphate (NADPH)-dependent bidirectional enzyme that can interconvert inactive cortisone to active cortisol, predominantly as a reductase enzyme. 11β-HSD type 2 is a high-affinity nicotinamide adenine dinucleotide (NAD)-dependent unidirectional enzyme with dehydrogenase action and inactivates cortisol to cortisone. Reductase activity for physiological glucocorticoids has not been seen for 11β-HSD type 2

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