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