Isoquercitrin Attenuates Osteogenic Injury in MC3T3 Osteoblastic Cells and the Zebrafish Model via the Keap1-Nrf2-ARE Pathway.

Isoquercitrin (IQ) widely exists in natural products, with a variety of pharmacological activities. In this study, the anti-apoptotic and antioxidative activities of IQ were evaluated. IQ showed protective activity against 2, 2'-azobis [2-methylpropionamidine] dihydrochloride (AAPH)-induced cell damage, as well as a marked reduction in reactive oxygen species (ROS). The evidence of IQ regulating Keap1-Nrf2-ARE and the mitochondrial-mediated Caspase 3 pathway were found in the MC3T3 osteoblastic cell line. Furthermore, IQ significantly decreased ROS production, apoptosis, and lipid peroxidation in AAPH-treated 72 h post-fertilization (hpf) zebrafish, as observed via DCFH-DA, acridine orange (AO), and a 1,3-bis(diphenylphosphino) propane (DPPP) probe, respectively. In AAPH-treated 9 day post-fertilization (dpf) zebrafish, IQ strongly promoted osteogenic development, with increased concentrations by calcein staining, compared with the untreated group. In a molecular docking assay, among all signal proteins, Keap1 showed the strongest affinity with IQ at -8.6 kcal/mol, which might be the reason why IQ regulated the Keap1-Nrf2-ARE pathway in vitro and in vivo. These results indicated that IQ promotes bone development and repairs bone injury, which is valuable for the prevention and treatment of bone diseases.

Pubmed ID: 35684398 RIS Download