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异槲皮苷通过 Keap1-Nrf2-ARE 通路减轻 MC3T3 成骨细胞和斑马鱼模型的成骨损伤。

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

机构信息

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.

出版信息

Molecules. 2022 May 27;27(11):3459. doi: 10.3390/molecules27113459.

DOI:10.3390/molecules27113459
PMID:35684398
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9182080/
Abstract

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.

摘要

异槲皮苷（IQ）广泛存在于天然产物中，具有多种药理活性。本研究评估了 IQ 的抗细胞凋亡和抗氧化活性。IQ 对 2,2'-偶氮双[2-甲基丙脒]二盐酸盐（AAPH）诱导的细胞损伤具有保护作用，并显著减少活性氧（ROS）。在 MC3T3 成骨细胞系中发现了 IQ 调节 Keap1-Nrf2-ARE 和线粒体介导的 Caspase 3 途径的证据。此外，IQ 可显著降低 AAPH 处理后 72 hpf 斑马鱼的 ROS 产生、凋亡和脂质过氧化，通过 DCFH-DA、吖啶橙（AO）和 1,3-双（二苯基膦基）丙烷（DPPP）探针分别观察到。在 AAPH 处理后 9 dpf 斑马鱼中，IQ 通过钙黄绿素染色与未经处理的组相比，浓度显著增加，强烈促进成骨发育。在分子对接实验中，在所有信号蛋白中，Keap1 与 IQ 的亲和力最强，为-8.6 kcal/mol，这可能是 IQ 在体外和体内调节 Keap1-Nrf2-ARE 途径的原因。这些结果表明，IQ 促进骨骼发育和修复骨损伤，这对于预防和治疗骨骼疾病具有重要价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1485/9182080/ab65f62e8001/molecules-27-03459-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1485/9182080/035cd2058899/molecules-27-03459-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1485/9182080/fdc54d9b18b5/molecules-27-03459-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1485/9182080/9a20431186f5/molecules-27-03459-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1485/9182080/5e9461ed69bd/molecules-27-03459-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1485/9182080/ab65f62e8001/molecules-27-03459-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1485/9182080/035cd2058899/molecules-27-03459-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1485/9182080/fdc54d9b18b5/molecules-27-03459-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1485/9182080/9a20431186f5/molecules-27-03459-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1485/9182080/5e9461ed69bd/molecules-27-03459-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1485/9182080/ab65f62e8001/molecules-27-03459-g005.jpg

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