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Glycyrrhizic acid (GCA) as 11β-hydroxysteroid dehydrogenase inhibitor exerts protective effect against glucocorticoid-induced osteoporosis

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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.

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Acknowledgments

This work was supported by the Malaysian Ministry of Science Technology and Innovation (MOSTI) and Universiti Kebangsaan Malaysia (UKM) Research Grant. The authors gratefully acknowledge the technical assistance of the staffs of the Anatomy and Pharmacology Department of Universiti Kebangsaan Malaysia; especially Mrs Azizah Othman, Mrs Mazlidiyana and Mr Rafizul.

Conflict of interest

The authors declare that they have no conflict of interest regarding this paper.

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Authors and Affiliations

  1. Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    Elvy Suhana Mohd Ramli, Farihah Suhaimi, Siti Fadziyah Mohamad Asri & Fairus Ahmad

  2. Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    Ima Nirwana Soelaiman

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  1. Elvy Suhana Mohd Ramli
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Correspondence to Ima Nirwana Soelaiman.

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Ramli, E.S.M., Suhaimi, F., Asri, S.F.M. et al. Glycyrrhizic acid (GCA) as 11β-hydroxysteroid dehydrogenase inhibitor exerts protective effect against glucocorticoid-induced osteoporosis. J Bone Miner Metab 31, 262–273 (2013). https://doi.org/10.1007/s00774-012-0413-x

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  • DOI: https://doi.org/10.1007/s00774-012-0413-x

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