key: cord-0718014-efia3d0y authors: Diep, Phuoc-Tan title: TRPV1, Nrf2, and COVID-19: Could Oxytocin Have a Beneficial Role to Play? date: 2022-01-03 journal: Int Arch Allergy Immunol DOI: 10.1159/000521246 sha: c646c1f5e89fd8123b6e5e789ed53aaab23dba42 doc_id: 718014 cord_uid: efia3d0y nan Dear Editor, Bousquet et al. [1] have elegantly and very informatively linked TRPV1, Nrf2, nutrients, and COVID-19: "rapid desensitization of TRAP1/TRPV1 by some ingredients in foods could reduce symptom severity and provide new therapeutic strategies." I would like to strengthen their links and proffer a peptide that could be important to their hypothesis: oxytocin. Oxytocin is known for its function in labour and lactation and as the "love" hormone. However, it has numerous other actions and these actions provide additional supportive links and data. It is interesting to note that many of the "Nrf2-, TRPA1-, and TRPV1-interacting nutrients" (see Table 1 Bousquet et al. [1]) can also increase oxytocin or improve its function: Lactobacillus [9] , quercetin [10] , zinc [11] , vitamin C [12] , and vitamin D [13] . In another paper, Bousquet et al. [14] note that Nrf2-interacting nutrients also act on "mTOR, mammalian target of rapamycin; PPARγ, peroxisome proliferator-activated receptor; NFκB, nuclear factor kappa B; ERK, extracellular signalregulated kinases; and eIF2α, elongation initiation factor 2α." Oxytocin also acts on these (in animal and in vitro studies): mTOR [15] , PPARγ [16] , NFκB [17] , ERK [18] , and eIF2α [19] . Therefore, the endogenous neurohormone, oxytocin, is capable of both inhibiting TRPV1 and increasing Nrf2, and modulating numerous other pathways. This adds to the complexity of the link between TRPV1 and Nrf2. This also raises some questions and gaps in knowledge. Does oxytocin act as part of a nutrient-oxytocin-Nrf2 pathway or does it act in parallel? In addition, can oxytocin act synergistically with these nutrients? Not surprisingly, oxytocin has already been proposed as a treatment for COVID-19 due to numerous anti-inflammatory properties [16] , antioxidant properties [20] , anti-diabetic properties [21, 22] , cardioprotective properties [23] , and even possible direct antiviral properties [24] . It is safe and easily administered intranasally [25] . I hope these additional links will advance the understanding of how TRPV1, Nrf2, and nutrients interact, and therefore, strengthen Bousquet's hypothesis and importantly, I hope this will lead to further research in this area and new therapeutic strategies. Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin Bisfenol effect of quercetin on cortisol and oxytocin levels, oxytocin receptor gene expression and morphometry of uterus in rats exposed to bisphenol A Oxytocin-receptor binding: why divalent metals are essential The time-course of oxytocin secretion from cultured bovine granulosa cells, stimulated by ascorbate and catecholamines Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies Oxytocin modulates mTORC1 pathway in the gut Can intravenous oxytocin infusion counteract hyperinflammation in COVID-19 infected patients Oxytocin effects on the inhibition of the NF-κB/miR195 pathway in mice breast cancer Extracellular signal-regulated kinase 1/2 activation by myometrial oxytocin receptor involves Galpha(q)Gbetagamma and epidermal growth factor receptor tyrosine kinase activation Oxytocin suppresses inflammatory responses induced by lipopolysaccharide through inhibition of the eIF-2-ATF4 pathway in mouse microglia Oxytocin inhibits NADPH oxidase and P38 MAPK in cisplatin-induced nephrotoxicity Two birds with one stone: possible dual-role of oxytocin in the treatment of diabetes and osteoporosis. Front Endocrinol Oxytocin may be superior to gliptins as a potential treatment for diabetic COVID-19 patients Cardiovascular protective properties of oxytocin against CO-VID-19 Hypothesis: oxytocin is a direct COVID-19 antiviral. Med Hypotheses Evidence for intranasal oxytocin delivery to the brain: recent advances and future perspectives