Potential Interplay between Nrf2, TRPA1, and TRPV1 in Nutrients for the Control of COVID-19

Abstract

In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or transient receptor potential vanilloid 1 (TRPV1) activation as well as desensitization. TRPA1 and TRPV1 induce inflammation and play a key role in the physiology of almost all organs. They may augment sensory or vagal nerve discharges to evoke pain and several symptoms of COVID-19, including cough, nasal obstruction, vomiting, diarrhea, and, at least partly, sudden and severe loss of smell and taste. TRPA1 can be activated by reactive oxygen species and may therefore be up-regulated in COVID-19. TRPA1 and TRPV1 channels can be activated by pungent compounds including many nuclear factor (erythroid-derived 2) (Nrf2)-interacting foods leading to channel desensitization. Interactions between Nrf2-associated nutrients and TRPA1/TRPV1 may be partly responsible for the severity of some of the COVID-19 symptoms. The regulation by Nrf2 of TRPA1/TRPV1 is still unclear, but suggested from very limited clinical evidence. In COVID-19, it is proposed that rapid desensitization of TRAP1/TRPV1 by some ingredients in foods could reduce symptom severity and provide new therapeutic strategies.

The Combined Effect of Branching and Elongation on the Bioactivity Profile of Phytocannabinoids. Part I: Thermo-TRPs

“…The desensitization of TRPA1 has the potential to translate into beneficial effects for a wide range of inflammatory conditions [25], traditionally focused in the realm of inflammation and pain [20]. However, growing evidence of involvement in the SARS-CoV-2 infection through the modulation of inflammation, pain, and fever, has provided an additional therapeutic area of investigation, with documented proof-of-concept clinical cases of the beneficial effects of sulforafane, a TRPA1 and Nrf2-interacting nutrient, on the course of the infection [7].…”

“…Phytocannabinoids are multi-target agents, capable of modulating a variety of endpoints that includes not only metabotropic receptors (CB 1 , CB 2 ), but also enzymes, nuclear receptors, and ionotropic receptors belonging to the family of thermo-TRPs (TRPV1-V4, TRPM8, TRPA1) [5]. In particular, thermo-TRPs represent relevant pharmacological targets in a wide array of pathological conditions ranging from pain to inflammatory and respiratory diseases [6], including those linked to COVID-19 [7]. Surprisingly, no systematic attempt has been made so far to investigate the effect of branching and elongation on the overall biological profile of phytocannabinoids.…”

Transient Receptor Potential Vanilloid Subtype 1: Potential Role in Infection, Susceptibility, Symptoms and Treatment of COVID-19

“…Many signaling pathways including calmodulin, calcineurin, or the decrease of phosphatidylinositol 4,5-bisphosphate, are involved in TRPV-1 desensitization. Oxidative stress reduces phosphatidylinositol 4,5-bisphosphate, and receptor desensitization could be reached at lower doses of agonists in SARS-Cov-2 infection ( 5 ). Tachyphylaxis, defined as a reduction in the response after frequent applications of agonists, is another type of desensitization of TRPV-1 by CPS ( 126 ).…”

“…Furthermore, the pathophysiology in COVID-19 patients is similar to the effects generated by TRPV-1 stimulation ( 3 ). Finally, treatment with agonists that down-regulate or inactivate TRPV-1 may have a beneficial effect on impaired lung function ( 3 – 5 ), and clearance of infection ( 6 ). In this review, we explore the role of TRPV-1 channel in the infection, susceptibility, pathogenesis, and treatment of SARS-CoV-2 infection.…”

Spices for taming the COVID-19 pandemic: Prospects and perspectives

“…TRPA1, playing a key role in the physiology of almost all organs, induces inflammation, while TRPV1 detects and regulates body temperature (Fernandes et al 2012). Both the TRP ion channels are associated with control of weight, pancreatic function, hormone secretion, thermogenesis, and neuronal function and are sensory receptors for multiple products of oxidative stress (Bousquet et al 2021). They, especially TRPV1-expressing neuronal systems (afferent/efferent neurons) in the lungs, are closely linked with many physiological events that lead to mortality.…”