Affiliation: | aInstitute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel bLaboratory of Natural Medicinal Compounds, Migal-Galilee Technological Center, Kiryat Shmona 10200, Israel cDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel dDepartment of Orthopaedic Surgery, Sharei-Zedek Medical Center, Jerusalem, Israel eDepartment of Chemistry, Johns Hopkins University, Baltimore, MD, USA |
Abstract: | Data from both in vivo and in vitro experiments demonstrated that glabridin and glabrene are similar to estradiol-17β in their stimulation of the specific activity of creatine kinase, although at higher concentrations, but differ in their extent of action and interaction with other drugs. In pre-menopausal human bone cells, the response to estradiol-17β and glabridin (at higher concentration) was higher than in post-menopausal cells; whereas, glabrene (at higher concentration) was more effective in post-menopausal cells. At both ages, the response to estradiol-17β and glabridin was enhanced by pretreatment with the less-calcemic Vitamin D analog CB 1093 (CB) and the demonstrably non-calcemic analog JK 1624 F2-2 (JKF). The response to glabrene was reduced by this pretreatment. Both glabridin and glabrene stimulated creatine kinase specific activity in diaphyseal bone and epiphyseal cartilage of prepubertal female rats. Daily feeding (3–14 days) of prepubertal female rats with glabridin, estradiol-17β or their combination, also stimulated creatine kinase specific activity. Glabridine, similarly to estradiol-17β, also stimulated creatine kinase specific activity in ovariectomized female rats. Raloxifene, in combination with glabridin or estradiol-17β, demonstrated the phenomenon of mutual annihilation of stimulation of creatine kinase specific activity in both epiphysis and diaphysis. Glabrene activity was not inhibited by raloxifene. Therefore, glabridin shows greater similarity to estradiol-17β and thus greater potential, with or without Vitamin D, to modulate bone disorders in post-menopausal women. |