Glabridin, an isoflavan purified from licorice root, exhibits diverse biological activities, including estrogen-like activity. To investigate the bioactivities of glabridin, which act on bone metabolism, the effects of glabridin on the function of mouse osteoblastic cell line (MC3T3-E1) and the production of local factors in osteoblasts were studied. Glabridin (1-10microM) significantly increased the growth of MC3T3-E1 cells and caused a significant elevation of alkaline phosphatase (ALP) activity, collagen content and osteocalcin secretion in the cells (P<0.05). The effect of glabridin (10microM) in increasing ALP activity and collagen content was completely prevented by the presence of 10(-6)M cycloheximide and 10(-6)M tamoxifen, suggesting that glabridin's effect results from a newly synthesized protein component and might be partly involved in estrogen action. Then, the effects of glabridin on the TNF-alpha-induced apoptosis and production of prostaglandin E2 (PGE2) and nitric oxide (NO) in osteoblasts were examined. Treatment with glabridin (1-10microM) prevented apoptosis induced by TNF-alpha (10(-10)M) in osteoblastic cells. Moreover, glabridin (50microM) decreased the 10(-10)M TNF-alpha-induced production of PGE2 and NO in osteoblasts. Our data indicate that the enhancement of osteoblast function by glabridin may result in the prevention for osteoporosis and inflammatory bone diseases.