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

Copyright © 2024 Elsevier Inc. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:705

Enthalten in:

Biochemical and biophysical research communications - 705(2024) vom: 23. März, Seite 149756

Sprache:

Englisch

Beteiligte Personen:

Singh, Jitender [VerfasserIn]
Bisht, Priyanka [VerfasserIn]
Srivastav, Srishti [VerfasserIn]
Kumar, Yash [VerfasserIn]
Sharma, Vikash [VerfasserIn]
Kumar, Ashish [VerfasserIn]
Akhtar, Md Sayeed [VerfasserIn]
Khan, Mohd Faiyaz [VerfasserIn]
Aldosari, Saad A [VerfasserIn]
Yadav, Snehlata [VerfasserIn]
Yadav, Nirmala K [VerfasserIn]
Mukherjee, Monalisa [VerfasserIn]
Sharma, Arun K [VerfasserIn]

Links:

Volltext

Themen:

Endothelial dysfunction
HFD-Induced obesity
Inflammatory cytokines
Journal Article
Ligands
Lipopolysaccharides
Myeloid Differentiation Factor 88
Myocardial infarction
NF-kappa B
Q369O8926L
Resveratrol
Stilbenes
TLR4/MyD88/NF-κB/iNOS pathway
Toll-Like Receptor 4

Anmerkungen:

Date Completed 19.03.2024

Date Revised 19.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.bbrc.2024.149756

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369501683