Nrf2, a central mechanism in insulin resistance, and severity of COVID-19
Nrf2 is a pleiotropic transcription factor at the centre of a complex regulatory network that protects against oxidative stress and the expression of a wide array of genes involved in immunity and inflammation, including antiviral actions.26 Nrf2 may be involved in diseases associated with insulin-resistance.27,28 Nrf2 activity declines with age, making the elderly more susceptible to oxidative stress-mediated diseases. Nrf2-activating compounds downregulate ACE2 mRNA expression in human liver-derived HepG2 cells,29 and in genes encoding cytokines including IL-6 and many others specifically identified in the ”cytokine storm” observed in fatal cases of COVID-19.
Natural compounds derived from plants, vegetables, fungi and micronutrients (e.g. curcumin, sulforaphane, resveratrol and vitamin D) can activate Nrf2.30 ACE2 can inhibit NF-κB and activate Nrf2.31