Isoquercitrin Attenuates Osteogenic Injury in MC3T3 Osteoblastic Cells and the Zebrafish Model via the Keap1-Nrf2-ARE Pathway
Xue Li,
Dongyue Zhou,
Di Yang,
Yunhua Fu,
Xingyu Tao,
Xuan Hu,
Yulin Dai,
Hao Yue
Affiliations
Xue Li
Jilin Ginseng Academy, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun University of Chinese Medicine, Changchun 130117, China
Dongyue Zhou
Jilin Ginseng Academy, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun University of Chinese Medicine, Changchun 130117, China
Di Yang
Jilin Ginseng Academy, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun University of Chinese Medicine, Changchun 130117, China
Yunhua Fu
Jilin Ginseng Academy, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun University of Chinese Medicine, Changchun 130117, China
Xingyu Tao
Jilin Ginseng Academy, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun University of Chinese Medicine, Changchun 130117, China
Xuan Hu
Jilin Ginseng Academy, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun University of Chinese Medicine, Changchun 130117, China
Yulin Dai
Jilin Ginseng Academy, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun University of Chinese Medicine, Changchun 130117, China
Hao Yue
Jilin Ginseng Academy, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun University of Chinese Medicine, Changchun 130117, China
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.
