The anti-inflammatory and immunomodulatory properties of flavonoids are well-described , , , , , . Thus, flavonoids could potentially be useful in the modulation of COVID-19-related inflammatory processes and immune responses.
Graphical abstract from Science Direct
Due to the excessive immune responses that trigger cytokine release and can result in the overproduction of proinflammatory cytokines, the modulation of systemic immune responses and reversion of hyper-inflammation are suggested to possess a potential role in the management of COVID-19 patients . Generally speaking, flavonoids can modulate the production of inflammatory mediators.
"The well-known capacity of flavonoids to regulate anti-viral, anti-inflammatory, and immunomodulatory responses underscores their potential importance also in the treatment of COVID-19. "
Although the results of studies utilizing flavonoids against COVID-19 published so far are promising, the body of literature on this topic as a whole remains partial and does not provide sufficient evidence for its applicability in COVID-19 patients. Nevertheless, current intensive research suggests the great potential of flavonoids as natural substances promoting the prevention or overcoming the SARS-CoV-2 infection due to the wide range of their biological effects including the modulation of inflammatory processes and immune responses.
Due to the extensive biological effects of flavonoids demonstrated in various pathologies, promising results are hypothesized also in the association of their usefulness in the management of COVID-19.
Based on the findings discussed in this review, the beneficial effects of flavonoids in the modulation of inflammatory and immune processes in COVID-19 can be expected.
Source from Science Direct
Graphical abstract from Science Direct: Inflammatory pathways associated with SARS-CoV-2 that can be potentially targeted by flavonoids
Abstract: The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of flavonoids in the modulation of signaling pathways that are crucial for COVID-19 disease, particularly those related to inflammation and immunity. The immunomodulatory ability of flavonoids, carried out by the regulation of inflammatory mediators, the inhibition of endothelial activation, NLRP3 inflammasome, toll-like receptors (TLRs) or bromodomain containing protein 4 (BRD4), and the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2), might be beneficial in regulating the cytokine storm during SARS-CoV-2 infection. Moreover, the ability of flavonoids to inhibit dipeptidyl peptidase 4 (DPP4), neutralize 3-chymotrypsin-like protease (3CLpro) or to affect gut microbiota to maintain immune response, and the dual action of angiotensin-converting enzyme 2 (ACE-2) may potentially also be applied to the exaggerated inflammatory responses induced by SARS-CoV-2. Based on the previously proven effects of flavonoids in other diseases or on the basis of newly published studies associated with COVID-19 (bioinformatics, molecular docking), it is reasonable to assume positive effects of flavonoids on inflammatory changes associated with COVID-19. This review highlights the current state of knowledge of the utility of flavonoids in the management of COVID-19 and also points to the multiple biological effects of flavonoids on signaling pathways associated with the inflammation processes that are deregulated in the pathology induced by SARS-CoV-2. The identification of agents, including naturally occurring substances such as flavonoids, represents great approach potentially utilizable in the management of COVID-19. Although not clinically investigated yet, the applicability of flavonoids against COVID-19 could be a promising strategy due to a broad spectrum of their biological activities.