title: Glycyrrhizic acid (GCA) as 11β-hydroxysteroid dehydrogenase inhibitor exerts protective effect against glucocorticoid-induced osteoporosis.
abstract: Rapid onset of bone loss is a frequent complication of systemic glucocorticoid therapy which may lead to fragility fractures. Glucocorticoid action in bone depends upon the activity of 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). Regulations of 11β-HSD1 activity may protect the bone against bone loss due to excess glucocorticoids. Glycyrrhizic acid (GCA) is a potent inhibitor of 11β-HSD. Treatment with GCA led to significant reduction in bone resorption markers. In this study we determined the effect of GCA on 11β-HSD1 activity in bones of glucocorticoid-induced osteoporotic rats. Thirty-six male Sprague-Dawley rats (aged 3 months and weighing 250-300 g) were divided randomly into groups of ten. (1) G1, sham operated group; (2) G2, adrenalectomized rats administered with intramuscular dexamethasone 120 μg/kg/day and oral vehicle normal saline vehicle; and (3) G3, adrenalectomized rats administered with intramuscular dexamethasone 120 μg/kg/day and oral GCA 120 mg/kg/day The results showed that GCA reduced plasma corticosterone concentration. GCA also reduced serum concentration of the bone resorption marker, pyridinoline and induced 11β-HSD1 dehydrogenase activity in the bone. GCA improved bone structure, which contributed to stronger bone. Therefore, GCA has the potential to be used as an agent to protect the bone against glucocorticoid induced osteoporosis.
authors.affiliation: Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia.
authors.forename: Elvy Suhana Mohd
authors.initials: ES
authors.lastname: Ramli
authors.forename: Farihah
authors.initials: F
authors.lastname: Suhaimi
authors.forename: Siti Fadziyah Mohamad
authors.initials: SF
authors.lastname: Asri
authors.forename: Fairus
authors.initials: F
authors.lastname: Ahmad
authors.forename: Ima Nirwana
authors.initials: IN
authors.lastname: Soelaiman
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000315:Adrenalectomy; D000596:Amino Acids / Q000097:blood; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000009:adverse effects; D019587:Dietary Supplements; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005938:Glucocorticoids / Q000009:adverse effects*; D019695:Glycyrrhizic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000596:Amino Acids; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D020011:Protective Agents; D015675:Osteocalcin; C015484:pyridinoline; D019695:Glycyrrhizic Acid; D003907:Dexamethasone; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003345:Corticosterone