benzofurans and prednisolone-acetate

Glucocorticoids (GCs) are widely used to treat a variety of autoimmune diseases, but long-term use can lead to osteoporosis. To elucidate the mechanism of osteoporosis caused by glucocorticoids and to find effective protective drugs/foods, osteoblasts treated by prednisolone acetate were studied and salvianolic acid B (Sal B) was added to osteoblasts. The results showed that Sal B increased the activity of ALP and stimulated the expression of ALP that had been suppressed by prednisolone acetate. To further study the mechanisms of the protective effect of Sal B on osteoblasts treated with prednisolone acetate, the effects of gene expression involved with bone formation and differentiation were studied. The results show that the mRNA and protein expression of Runx2, Osx, OCN, IGF-I, Col-I and HO-I was up-regulated by Sal B. In conclusion, by stimulating the osteoblast activity and the expression of genes related to bone formation and differentiation, Sal B had a protective effect on osteoblasts that had been treated with prednisolone acetate.

Topics: Animals; Benzofurans; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Insulin-Like Growth Factor I; Osteoblasts; Osteogenesis; Prednisolone; Rats; Rats, Sprague-Dawley; Transcription Factors; Up-Regulation

To assess in vitro myocilin (MYOC) expression in trabecular meshwork (TM) cells exposed to BOL-303242-X, a selective glucocorticoid receptor (GR) agonist (SEGRA), in comparison with dexamethasone (DEX), and prednisolone acetate (PA).. After drug treatment of monkey TM cultures, MYOC protein in conditioned media (CM) was measured by Western blot and densitometry. MYOC mRNA levels were analyzed by qRT-PCR. RU-486 was tested for antagonism of MYOC protein expression induced by DEX and BOL-303242-X.. Baseline MYOC protein released into CM and MYOC mRNA were detected. DEX or PA elicited dose-dependent increases in MYOC in CM and also in MYOC mRNA. BOL-303242-X effects typified partial agonism, with significantly reduced MYOC protein and mRNA, compared with DEX. Maximum efficacy for BOL-303242-X was 53% of that for DEX. Mean EC(50) across all strains tested was lower, but not significantly different, for BOL-303242-X versus DEX. Compared with DEX, MYOC mRNA levels were significantly lower in BOL-303242-X-treated TM cells at the highest doses tested. EC(50)s for PA were higher than DEX, for both myocilin protein and mRNA. RU-486 displayed a dose-dependent antagonism to drug-induced increases in myocilin levels.. In vitro quantitative assays of myocilin expression in TM cells can be used for characterizing anti-inflammatory drugs that are GR ligands. The results suggest that, compared with traditional ocular steroids, therapeutic doses of BOL-303242-X elicit a reduced myocilin expression profile in TM cells by virtue of the partial agonist properties of this compound.

Topics: Animals; Benzofurans; Blotting, Western; Cells, Cultured; Cytoskeletal Proteins; Dexamethasone; Dose-Response Relationship, Drug; Eye Proteins; Gene Expression; Glucocorticoids; Glycoproteins; Hormone Antagonists; Macaca mulatta; Mifepristone; Pentanols; Prednisolone; Quinolines; Receptors, Glucocorticoid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Trabecular Meshwork