PMID- 35684398 OWN - NLM STAT- MEDLINE DCOM- 20220613 LR - 20220716 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 27 IP - 11 DP - 2022 May 27 TI - Isoquercitrin Attenuates Osteogenic Injury in MC3T3 Osteoblastic Cells and the Zebrafish Model via the Keap1-Nrf2-ARE Pathway. LID - 10.3390/molecules27113459 [doi] LID - 3459 AB - 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. FAU - Li, Xue AU - Li X AD - 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. FAU - Zhou, Dongyue AU - Zhou D AD - 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. FAU - Yang, Di AU - Yang D AD - 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. FAU - Fu, Yunhua AU - Fu Y AD - 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. FAU - Tao, Xingyu AU - Tao X AD - 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. FAU - Hu, Xuan AU - Hu X AD - 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. FAU - Dai, Yulin AU - Dai Y AD - 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. FAU - Yue, Hao AU - Yue H AD - 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. LA - eng GR - 20210401065YY/Scientific and Technological Development Program of Jilin province of China/ GR - 20210204046YY/Scientific and Technological Development Program of Jilin province of China/ PT - Journal Article DEP - 20220527 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Kelch-Like ECH-Associated Protein 1) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Reactive Oxygen Species) RN - 0YX10VRV6J (isoquercitrin) RN - 9IKM0I5T1E (Quercetin) SB - IM MH - Animals MH - Apoptosis MH - Kelch-Like ECH-Associated Protein 1/metabolism MH - Molecular Docking Simulation MH - *NF-E2-Related Factor 2/metabolism MH - Oxidative Stress MH - Quercetin/analogs & derivatives MH - Reactive Oxygen Species/metabolism MH - Signal Transduction MH - *Zebrafish/metabolism PMC - PMC9182080 OTO - NOTNLM OT - antioxidant OT - isoquercitrin OT - osteogenic development COIS- The authors declare no conflict of interest. EDAT- 2022/06/11 06:00 MHDA- 2022/06/14 06:00 PMCR- 2022/05/27 CRDT- 2022/06/10 01:24 PHST- 2022/04/05 00:00 [received] PHST- 2022/05/21 00:00 [revised] PHST- 2022/05/26 00:00 [accepted] PHST- 2022/06/10 01:24 [entrez] PHST- 2022/06/11 06:00 [pubmed] PHST- 2022/06/14 06:00 [medline] PHST- 2022/05/27 00:00 [pmc-release] AID - molecules27113459 [pii] AID - molecules-27-03459 [pii] AID - 10.3390/molecules27113459 [doi] PST - epublish SO - Molecules. 2022 May 27;27(11):3459. doi: 10.3390/molecules27113459.