The endogenous

DZNeP mw glucocorticoids were replaced by predetermined doses of dexamethasone to ensure a constant level of glucocorticoid in the body. The animals were also given normal saline ad libitium to maintain normal sodium homeostasis.22 The dose and duration of dexamethasone treatment for the induction of osteoporosis were determined by a pilot study. The doses of the GCA and Piper sarmentosum water extract were also determined based on previous studies.23,24 Dexamethasone is a synthetic glucocorticoid, which is 20-30 and five times more potent than hydrocortisone Inhibitors,research,lifescience,medical and prednisolone, respectively. It is able Inhibitors,research,lifescience,medical to bind to glucocorticoid receptors (GRα). Long-term dexamethasone treatment causes significant reduction in mineral density, calcium content, and length of the femur of adrenalectomized rats.22 That study showed that long-term dexamethasone treatment caused a significant reduction in local 11β-HSD 1 dehydrogenase activity, but increased the expression of 11β-HSD1 in the bone. The study also showed that long-term glucocorticoid treatment led to a defect in dehydrogenase activity in the bone. Defective dehydrogenase activity

might have been associated with an increase in the reductase activity, which led to an increase in the conversion of inactive cortisone to active Inhibitors,research,lifescience,medical cortisol. This would lead to an increase in the local availability of active glucocorticoids in the bone,25,26 which subsequently

would increase the risk of developing glucocorticoid-induced Inhibitors,research,lifescience,medical osteoporosis. The expression of 11β-HSD1 enzyme in the bones of dexamethasone-treated rats was greater than Inhibitors,research,lifescience,medical that in the sham-operated group. This is consistent with the finding of a previous study, which reported that cortisol and dexamethasone increased the expression of 11β-HSD1 mRNA in a primary osteoblast culture.27 Increase in the 11β-HSD1 enzyme expression could be due to an increase in synthesis of the enzyme. ADP ribosylation factor Possibly, a larger proportion of 11β-HSD1 enzyme expressed in the bone demonstrated a higher reductase activity, and this caused an increase in the local availability of active glucocorticoids in the bone in agreement with a previous study.13 Supplementing the dexamethasone-treated adrenalectomized rats with Piper sarmentosum water extract and GCA resulted in a significant increase in dehydrogenase activity. Supplementing dexamethasone-treated rats with Piper sarmentosum extract may have inhibited the reductase activity of the enzyme, and switched its action to dehydrogenase activity. It was reported in a previous ‘in vitro’ study that GCA totally inhibited the dehydrogenase activity of dexamethasone-treated osteoblast cells.