Inhibitory effect of 5-hydroxy-6,7-dimethoxyflavone on H1N1 influenza virus-induced ferroptosis and inflammation in A549 cells and its possible mechanisms
10.12122/j.issn.1673-4254.2024.06.07
- VernacularTitle:5-羟基-6,7-二甲氧基黄酮抑制流感病毒诱导A549细胞炎症反应和铁死亡的作用及机制
- Author:
Zhixian REN
1
;
Beixian ZHOU
;
Linxin WANG
;
Jing LI
;
Rongping ZHANG
;
Xiping PAN
Author Information
1. 云南中医药大学中药学院暨云南省南药可持续利用研究重点实验室,云南 昆明 650500
- Keywords:
Elsholtzia blanda Benth.;
5-hydroxy-6,7-dimethoxyflavone;
ferroptosis;
anti-inflammation;
influenza virus
- From:
Journal of Southern Medical University
2024;44(6):1070-1078
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone(5-HDF),a compound extracted from Elsholtzia blanda Benth.,against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action.Methods 5-HDF was extracted from Elsholtzia blanda Benth.using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses.In an A549 cell model of H1N1 influenza virus infection(MOI=0.1),the cytotoxicity of 5-HDF was assessed using MTT assay,and its effect on TRAIL and IL-8 expressions was examined using flow cytometry;Western blotting was used to detect the expression levels of inflammatory,apoptosis,and ferroptosis-related proteins.In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 μL H1N1 virus at the median lethal dose,the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight,lung index,gross lung anatomy and lung histopathology were observed.Results 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 μg/mL.In H1N1-infected A549 cells,treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65,lowered the expressions of IL-8,enhanced the expression of anti-ferroptosis proteins(SLC7A11 and GPX4),and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL.In H1N1-infected mice,treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies.Conclusion 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis,inflammatory responses,and apoptosis via upregulating SLC7A11 and GPX4,inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK,and decreasing the expression of cleaved caspase3 and cleaved PARP.
