Abstract
Myricetin belongs to the flavonoid family which is derived from plant source. It is well-known for the anti-inflammatory and anti-oxidative properties yet the clinical use of myricetin awaits further discovery. Acute lung injury (ALI) is commonly caused by sepsis which leads to enormous burden with high morbidity and mortality. In this study, a murine sepsis model was constructed by cecal ligation and puncture (CLP). The indicated dose of myricetin (100 mg/kg) was further administrated intragastrically. The survival rate test indicated that myricetin significantly improved the vitality of CLP-operated mice. The pathological changes in morphology, biomarkers of inflammatory response, oxidative stress response, and mitochondrial damage were further detected. Myricetin showed significant inhibitory effects on these changes in CLP-induced mice. Furthermore, expression levels of transcription factor Nrf2 and heme oxygenase-1 (HO-1) along with DNA binding activity of Nrf2 were analyzed by western blot and EMSA, indicating that myricetin positively regulates the Nrf2/HO-1 pathway in CLP-induced sepsis mice. Murine sepsis models with knockdown of Nrf2 and control were further established and suggested that myricetin might exert protective effects on sepsis lung injury in dependent with Nrf2. Our study provides novel mechanisms for the protective effect of myricetin in sepsis-associated acute lung injury.
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XY conceived and designed research. HX and QQ conducted experiments and collected data. HX analyzed data. HX and XY wrote the manuscript. All authors read and approved the manuscript.
Besides, we state that all the data were generated in-house, and we did not use a paper mill.
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All experiments have been approved by the Institutional Ethics Animal Committee of Hebei Medical University with the official approval number (No. 2020-P009). All operations were conducted according to the guideline for the care and use of laboratory animals.
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Xu, H., Qi, Q. & Yan, X. Myricetin ameliorates sepsis-associated acute lung injury in a murine sepsis model. Naunyn-Schmiedeberg's Arch Pharmacol 394, 165–175 (2021). https://doi.org/10.1007/s00210-020-01880-8
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DOI: https://doi.org/10.1007/s00210-020-01880-8