Proposed mechanisms of action of Kimchi and fermented vegetables in COVID 19
Reactive oxygen species (ROS), such as hydrogen peroxide and superoxide anion, exert beneficial and toxic effects on cellular functions. Nrf2 is a key regulator of the anti-oxidative response.47 Nrf2 activity in response to chemical insults is regulated by a thiol-rich protein named KEAP1 (Kelch-like ECH-associated protein 1). The KEAP1-Nrf2 system is the body’s dominant defense mechanism against ROS.48 Sulforaphane is the most potent activator of Nrf2 3,34. “Ancient foods”, and particularly those containing Lactobacillus, activate Nrf2.49 In different animal models, several strains of Lactobacillus were found to regulate Nrf2.50-52 In vitro studies have shown an effect of Lactobacillus on Nrf2.53-55
A putative mechanism may be proposed (Figure 2). SARS-CoV-2 downregulates ACE2 inducing an increased insulin resistance associated with oxidative stress through the AT1R pathway. Fermented vegetables are often made from cruciferous (Brassica) vegetables that release glucoraphanin converted by the plant or by the gut microbiome into sulforaphane which activates Nrf2 and subsequently reduces insulin intolerance by its potent antioxidant activities. Fermented vegetables contain a high content of Lactobacillus that can activate Nrf2 and impact on the microbiome. Nrf2 may be involved in diseases associated with insulin-resistance 24,56-58and may have a role in COVID-19. 59 Sulforaphane and LABs both have the ability to reduce insulin resistance.
Other putative actions on COVID-19 severity may be postulated. The down-regulation of ACE2 reduces the Ang-1,7 anti-oxidant activity that was found to activate Nrf2. 60,61 Nrf2 protects against hallmarks of severe COVID-19. It has anti-fibrotic effects on various organs including the lungs, 62 protects against lung injury and acute respiratory distress syndrome,63 and endothelial damage, 64 . Finally, Nrf2 can block IL-6 in different models of inflammation65 and might play a role in the COVID-19 cytokine storm.
These different mechanisms may explain the importance of fermented cabbage in preventing the severity of COVID-19. It is clear that other nutrients, vitamin D and many different foods act on NRF2.
It is not yet known whether sulforaphane and/or LABs may act on the infectivity of SARS-CoV-2. Disulfide bonds can be formed under oxidizing conditions and play an important role in the folding and stability of some proteins. The receptor-binding domain of the viral spike proteins and ACE2 have several cysteine residues. Using molecular dynamics simulations, the binding affinity was significantly impaired when all of the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. This computational finding possibly provides a molecular basis for the differential COVID-19 cellular recognition due to the oxidative stress.66