Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0205700 (ash)
 15,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

OST-6, a herbomineral preparation, was studied for its inhibitory effects on the progress of bone loss induced by ovariectomy (OVX) and concurrent calcium deficiency in rats. Calcium deficient ovariectomized rats were administered with OST-6 at 250 mg/kg b. w. twice a day orally for 16 weeks. Compared with sham operated animals, OVX animals showed an increase in serum ALP, urinary excretion of calcium and phosphorus, which were significantly prevented in OST-6 administered rats. Evaluation of cortical bone morphometric indices by CT-Scanning technique showed an increased medullary width and cross-sectional medullary area (MA), decreased periosteal area (PA), combined cortical thickness (CCT), cortical area/periosteal area (CA/PA) and maximal metaphyseal radial density (MMRD) in OVX animals when compared with sham operated. OST-6 treatment significantly prevented these bone resorption variables. Scanning Electron Microscopy (SEM) study revealed porous and erosive appearance of femur bone at the epiphyseal region and decreased calcium to phosphorus ratio (Ca:P) in the OVX rats when compared with sham operated rats. The treatment with OST-6 prevented the epiphyseal bone resorption and maintained Ca:P ratio. The results of ash analysis indicated a reduced bone mineral content (calcium and phosphorus) and ash weight and percent ash in OVX animals when compared with sham operated animals. All results are statistically significant at P < 0.05. These finding suggest the usefulness of OST-6 in the prevention of bone loss in a natural way through utilization of herbal resources.
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PMID:Prevention of bone loss in calcium deficient ovariectonized rats by OST-6, a herbal preparation. 1264 24

Human cathepsin K, a cysteine proteinase of the papain family, has been recognized as a potential drug target for the treatment of osteoporosis. The predominant expression of cathepsin K in osteoclasts has rendered the enzyme into a major target for the development of novel antiresorptive drugs. Now, we report the pharmacological properties of OST-4077 [furan-2-carboxylic acid (1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide] as a novel selective cathepsin K inhibitor. Human and rat cathepsin K were inhibited in vitro by OST-4077 with the IC50 values of 11 and 427 nM, respectively. OST-4077 suppressed bone resorption induced by rabbit osteoclasts (IC50, 37 nM) but did not affect bone mineralization or cellular alkaline phosphatase activity in MC3T3-E1 cells. Parathyroid hormone-induced bone resorption was inhibited in a dose-dependent manner in thyroparathyroidectomized rats gavaged with a single dose of OST-4077 (ED50, 69 mg/kg). When given orally twice daily for 4 weeks to 3-month-old ovariectomized (OVX) rats, OST-4077 dose-dependently prevented bone loss, as monitored by bone densitometry, ash content, and urinary excretion of deoxypyridinoline. No change in serum osteocalcin in the OVX rats by OST-4077 suggested that bone formation might not be affected by the agent. In summary, OST-4077 selectively inhibited bone resorbing activities of osteoclasts and prevented bone loss induced by estrogen deficiency but did not affect bone formation. OST-4077, an orally active selective human cathepsin K inhibitor, may have the therapeutic potential for the treatment of diseases characterized by excessive bone loss including osteoporosis.
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PMID:An orally active cathepsin K inhibitor, furan-2-carboxylic acid, 1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide (OST-4077), inhibits osteoclast activity in vitro and bone loss in ovariectomized rats. 1669 68