Resveratrol as an Adjunctive Therapy for Excessive Oxidative Stress in Aging COVID-19 Patients

Abstract

The coronavirus disease 2019 (COVID-19) pandemic continues to burden healthcare systems worldwide. COVID-19 symptoms are highly heterogeneous, and the patient may be asymptomatic or may present with mild to severe or fatal symptoms. Factors, such as age, sex, and comorbidities, are key determinants of illness severity and progression. Aging is accompanied by multiple deficiencies in interferon production by dendritic cells or macrophages in response to viral infections, resulting in dysregulation of inflammatory immune responses and excess oxidative stress. Age-related dysregulation of immune function may cause a more obvious pathophysiological response to SARS-CoV-2 infection in elderly patients and may accelerate the risk of biological aging, even after recovery. For more favorable treatment outcomes, inhibiting viral replication and dampening inflammatory and oxidative responses before induction of an overt cytokine storm is crucial. Resveratrol is a potent antioxidant with antiviral activity. Herein, we describe the reasons for impaired interferon production, owing to aging, and the impact of aging on innate and adaptive immune responses to infection, which leads to inflammation distress and immunosuppression, thereby causing fulminant disease. Additionally, the molecular mechanism by which resveratrol could reverse a state of excessive basal inflammatory and oxidative stress and low antiviral immunity is discussed.

Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic

“…Additionally, in terms of individual genes in the turquoise module, we identified hub-high traffic genes such as UTP14A ( 398 ), RUVBL2 ( 139 ), PRKCD ( 280 , 399 ), KEAP1 ( 400 – 402 ), CEBPA (TF) ( 403 ), RPL26L1 ( 404 ), PTPN6 ( 255 ), PPARA (TF) ( 405 ), TNFRSF1A ( 406 – 408 ), IKBKB ( 275 , 409 ), TFEB (TF) ( 410 , 411 ), PSMD4 ( 412 ), and ARHGAP1 ( 413 ), important components in immunopathogenesis of SARS-CoV-2. For example, the TNF receptor superfamily member 1A ( TNFRSF1A ) hub-high traffic gene may be a biomarker of mortality in severe COVID-19 patients, as increased expression of this gene was significantly correlated with mortalities ( 414 ).…”

Sustained Release of Co-Amorphous Matrine-Type Alkaloids and Resveratrol with Anti-COVID-19 Potential

“…Oxymatrine (OMAR) and sophoridine (SPD, Scheme 1) are matrine-type alkaloids isolated from S. flavescens Ait with promising biological activities [16,17], including antiviral activity [18,19]. Resveratrol (RES) is a plant polyphenol, which has also been used to treat COVID-19 patients with mild symptoms or as adjuvant supplements due to its anti-SARS-CoV-2 and anti-inflammatory activities [20,21]. However, matrine was given to COVID-19 patients via intravenous infusion [9], suggesting its poor pharmacokinetic properties, which may result in poor patient compliance and persistence, as well as unsatisfactory outcomes.…”

“…Oxymatrine (OMAR) and sophoridine (SPD, Scheme 1 ) are matrine-type alkaloids isolated from S. flavescens Ait with promising biological activities [ 16 , 17 ], including antiviral activity [ 18 , 19 ]. Resveratrol (RES) is a plant polyphenol, which has also been used to treat COVID-19 patients with mild symptoms or as adjuvant supplements due to its anti-SARS-CoV-2 and anti-inflammatory activities [ 20 , 21 ].…”

Resveratrol: Potential Application in Sepsis

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can strongly induce the release of cytokines and chemokines resulting in cytopathy and organ dysfunction. Resveratrol inhibits excessive inflammation and oxidative responses in elderly COVID-19 patients by activating Nrf2 in aging vascular smooth muscle cells to reduce the production of mitochondrial reactive oxygen species (ROS) ( Liao et al, 2021 ). Resveratrol may also play a positive role in sepsis-related injuries caused by viruses.…”