Resveratrol Downmodulates Neutrophil Extracellular Trap (NET) Generation by Neutrophils in Patients with Severe COVID-19

Abstract

The formation of microthrombi in lung autopsies indicates the involvement of NETs in the immunopathogenesis of severe COVID-19. Therefore, supplements inhibiting NET formation, in association with drugs with fewer adverse effects, should be a relevant strategy to attenuate the disease. Resveratrol (RESV) is a natural polyphenol with an important antiviral and antioxidant role. To modulate neutrophils from patients infected with SARS-CoV-2, we evaluated the in vitro effect of RESV on NET formation. Herein, we investigated 190 patients hospitalized with moderate, severe, and critical symptoms at Hospital das Clínicas, Brazil. We observed that neutrophilia in patients with severe COVID-19 infection is composed of neutrophils with activated profile able to release NET spontaneously. Notably, RESV decreased the neutrophil-activated status and the release of free DNA, inhibiting NET formation even under the specific PMA stimulus. At present, there is no evidence of the role of RESV in neutrophils from patients with COVID-19 infection. These findings suggest that adjunctive therapies with RESV may help decrease the inflammation of viral or bacterial infection, improving patient outcomes.

Exploration of the potential common pathogenic mechanisms in COVID-19 and silicosis by using bioinformatics and system biology

“…Angiotensin-converting enzyme-2 (ACE2), mainly expressed in endothelial cells, is a cell surface receptor that allows SARS-CoV-2 to enter cells. Multiple studies have revealed that resveratrol exerts its anti-COVID-19 and curative effects by reducing the expression of the ACE-2 receptor and alleviating oxidative stress (de Souza Andrade et al 2022 ; Domi et al 2022 ; Horne and Vohl 2020 ; van Brummelen and van Brummelen 2022 ). Silica-induced silicosis is characterized by progressive lung fibrosis, and previous studies have reported that resveratrol can inhibit pulmonary fibrosis (Chelladurai et al 2021 ; Wang et al 2018 , 2021 ).…”

Resveratrol prevents the release of neutrophil extracellular traps (NETs) by controlling hydrogen peroxide levels and nuclear elastase migration

“…Consequently, it is of utmost importance to identify safe drugs that can inhibit or reduce the release of NETs. Recent studies have shown that RSV significantly decreases the extrusion of spontaneous NET release in neutrophils obtained from COVID-19 patients and after stimulation of these neutrophils with PMA 52 .…”

Exploration of the link between COVID-19 and gastric cancer from the perspective of bioinformatics and systems biology

“…Resveratrol inhibits the progression of gastric cancer by anti-inflammatory, antioxidant [77], antibacterial [78], inducing cell cycle arrest [79], promoting apoptosis [80], and inhibiting proliferation [81]. Besides，resveratrol downregulates neutrophil extracellular traps (NETs) generation by neutrophils in patients with severe COVID-19 [82]. Similarly, network pharmacology has shown that resveratrol can alleviate COVID-19-related hyperinflammation [83].…”