Piper sarmentosum Prevents Glucocorticoid-Induced osteoporotic Bone Resorption by Increasing 11β-Hydroxysteroid Dehydrogenase Type 1 Activity
M.R. Elvy Suhana, H.S. Farihah, O. Faizah, S. Ahmad Nazrun, M. Norazlina, M. Norliza, S. Ima Nirwana
Aims. Osteoporosis is a proven complication of long-term glucocorticoid therapy. Concern on glucocorticoid induced osteoporosis has increased dramatically in recent years with the widespread use of synthetic glucocorticoids. Glucocorticoid action in bone depends upon the activity of 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). This enzyme plays an important role in regulating corticosteroids by locally interconverting cortisone into active cortisol. This has been demonstrated in primary cultures of human, mouse or rat osteoblasts. Therefore, inhibition of this enzyme may reduce bone resorption markers. Piper sarmentosum (Ps) is a potent inhibitor of 11β-HSD1 in liver and adipose tissue. In this study we determined the effect of Ps on 11β-HSD1 activity in bones of glucocorticoid-induced osteoporotic rats.
Materials and Methods. Three-month old male Sprague-Dawley rats were adrenalectomised to remove the main source of circulating glucocorticoids. The animals were administered with dexamethasone 120 µg/kg body weight/day. Treatment with Ps 125 mg/kg body weight and glycirrhizic acid (GCA) 120 mg/kg body weight were given simultaneously.
Results. The results showed that Ps extract reduced plasma corticosterone concentration (1.05+0.02µg/ml) and induced 11β-HSD1 dehydrogenase activity in bone (87.69+1.41%). Consequently, it also reduced the bone resorption marker, pyridinoline, in dexamethasone-treated adrenalectomised rats (2.07+0.62/L). Despite that, our data showed an inverse relationship between the plasma corticosterone level and the dehydrogenase activity of 11β-HSD1 in the bone.
Conclusions. This suggests that 11β-HSD1 acts as the local regulator of glucocorticoid and its activity in bone was not correlated to systemic corticosterone level. Clin Ter 2011; 162(4):313-318
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