AI Article Synopsis
- Researchers developed galloyl conjugates of flavanones that effectively promote osteoblast differentiation and bone formation.
- Studies indicated that one compound was particularly potent, active at a low concentration of 1 pM, and demonstrated its effectiveness in promoting osteogenic gene expression.
- In rat models, the compound increased key osteogenic genes and significantly enhanced bone regeneration at a dosage of 5 mg/(kg day), indicating strong potential for osteoporosis treatment.
Article Abstract
The molecular hybridization concept led us to design a series of galloyl conjugates of flavanones that have potent osteoblast differentiation ability and promote bone formation . An array of studies, especially gene expression of osteogenic markers, evinced compound as the most potent bone anabolic agent, found to be active at 1 pM, which was then further assessed for its osteogenic potential . From studies on rat calvaria and a fracture defect model, we inferred that compound , at an oral dose of 5 mg/(kg day), increased the expression of osteogenic genes (RUNX2, BMP-2, Col1, and OCN) and the bone formation rate and significantly promoted bone regeneration at the fracture site, as evidenced by the increased bone volume/tissue fraction compared with vehicle-treated rats. Furthermore, structure-activity relationship studies and pharmacokinetic studies suggest as a potential bone anabolic lead for future osteoporosis drug development.
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| http://dx.doi.org/10.1021/acs.jmedchem.1c00112 | DOI Listing |
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