Amelioration of endothelial integrity by 3,5,4′-trihydroxy-trans-stilbene against high-fat-diet-induced obesity and -associated vasculopathy and myocardial infarction in rats, targeting TLR4/MyD88/NF-κB/iNOS signaling cascade

Exacerbated expression of TLR4 protein (foremost pattern recognition receptor) during obesity could trigger NF-κB/iNOS signaling through linker protein (MyD88), predisposed to an indispensable inflammatory response. The induction of this detrimental cascade leads to myocardial and vascular abnormali...

Full description

Saved in:

Bibliographic Details
Published in:	Biochemical and biophysical research communications Vol. 705; p. 149756
Main Authors:	Singh, Jitender, Bisht, Priyanka, Srivastav, Srishti, Kumar, Yash, Sharma, Vikash, Kumar, Ashish, Akhtar, Md Sayeed, Khan, Mohd Faiyaz, Aldosari, Saad A., Yadav, Snehlata, Yadav, Nirmala K., Mukherjee, Monalisa, Sharma, Arun K.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 23-04-2024
Subjects:	Animals Diet Endothelial dysfunction HFD-Induced obesity Inflammatory cytokines Ligands Lipopolysaccharides - pharmacology Molecular Docking Simulation Myeloid Differentiation Factor 88 - metabolism Myocardial infarction Myocardial Infarction - drug therapy NF-kappa B - metabolism Rats Rats, Wistar Resveratrol Resveratrol - pharmacology Stilbenes - pharmacology Stilbenes - therapeutic use TLR4/MyD88/NF-κB/iNOS pathway Toll-Like Receptor 4 - metabolism TLR4/MyD88/NF-κB/iNOS pathway Myocardial infarction Endothelial dysfunction Inflammatory cytokines HFD-Induced obesity Resveratrol
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Exacerbated expression of TLR4 protein (foremost pattern recognition receptor) during obesity could trigger NF-κB/iNOS signaling through linker protein (MyD88), predisposed to an indispensable inflammatory response. The induction of this detrimental cascade leads to myocardial and vascular abnormalities. Molecular docking was studied for protein-ligand interaction between these potential targets and resveratrol. The pre-treatment of resveratrol (20 mg/kg/p.o/per day for ten weeks) was given to investigate the therapeutic effect against HFD-induced obesity and associated vascular endothelial dysfunction (VED) and myocardial infarction (MI) in Wistar rats. In addition to accessing the levels of serum biomarkers for VED and MI, oxidative stress, inflammatory cytokines, and histopathology of these tissues were investigated. Lipopolysaccharide (for receptor activation) and protein expression analysis were introduced to explore the mechanistic involvement of TLR4/MyD88/NF-κB/iNOS signaling. Assessment of in-silico analysis showed significant interaction between protein and ligand. The involvement of this proposed signaling (TLR4/MyD88/NF-κB/iNOS) was further endorsed by the impact of lipopolysaccharide and protein expression analysis in obese and treated rats. Moreover, resveratrol pre-treated rats showed significantly lowered cardio and vascular damage measured by the distinct down expression of the TLR4/MyD88/NF-κB/iNOS pathway by resveratrol treatment endorses its ameliorative effect against VED and MI. [Display omitted] •Obesity could trigger the inflammatory cytokines via TLR4/MyD88/NF-κB signaling.•TLR4/MyD88/NF-κB-iNOS pathway overexpression leads to vascular endothelial dysfunction and myocardial infarction.•Resveratrol ameliorates protein expression and vascular injury.•Conversely, resveratrol has no significant effect on obesity.•Reversal of protection by lipopolysaccharide administration signifies the involvement of TLR4/MyD88/NF-κB cascade.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-291X 1090-2104 1090-2104
DOI:	10.1016/j.bbrc.2024.149756