Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation <i>via</i> Inhibiting Autophagy and Programmed Cell Death.

Jin Hai YU; Guo Liang HU; Xiao Quan Guo; Hua Bin Cao; Zhao Fei Xia; Buhe Amin

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Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death.

Author: Jin Hai YU ¹ ; Guo Liang HU ¹ ; Xiao Quan GUO ¹ ; Hua Bin CAO ¹ ; Zhao Fei XIA ² ; Buhe AMIN ³
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1. Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, Jiangxi, China.
2. Internal Medicine Laboratory, Department of Veterinary Clinical Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100091, China.
3. Department of Cancer Surgery, Beijing Shijitan Hospital Affiliated with Capital Medical University, Beijing 100038, China.
Publication Type:Journal Article
Keywords: Autophagy; Inflammation; Lipopolysaccharide; Myocardiocytes permeability; Programmed cell death; Quercetin
MeSH: Chick Embryo; Animals; Quercetin/therapeutic use*; Lipopolysaccharides/toxicity*; Matrix Metalloproteinase 9; Caspase 3; Matrix Metalloproteinase 3; Toll-Like Receptor 4; Claudin-1; Inflammation/metabolism*; Apoptosis; RNA, Messenger; Autophagy; NF-kappa B
From: Biomedical and Environmental Sciences 2024;37(1):54-70
CountryChina
Language:English
Abstract: OBJECTIVE:The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction.
METHODS:Specific pathogen-free chicken embryos ( n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting.
RESULTS:They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1β, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.
CONCLUSION:Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.