Figure 1. Proinflammatory Angiotensin II, Interleukins, Tumour necrosis factor-α and Triggering receptor expressed on myeloid cells 1 (TREM-1) mediates the activation of Mitogen-activated protein kinase (MAPK), Extracellular signal-regulated kinase (ERK1/2) and Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) intracellular signalling pathways.

The downstream activators of these pathways induces the reactive oxygen species (ROS) generation and transcription factor, NF-κB dependent expression of proinflammatory molecules. HDACs, which deacetylates Signal transducer and activator of transcription 1 (STAT1), and promotes the nuclear translocation and subsequent activity of NF-κB. Target genes of NF-κB, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 increases the NF-κB activity via positive feedback loop. Histone deacetylase (HDAC) inhibitor, butyrate mediates its effects through GPCRs: Free fatty acid receptors 2/3 and GPCR 109A or by directly binding to HDAC active sites. Inhibition of NF-κB activity by butyrate attenuates inflammation and oxidative stress associated with various pathologies including CoVID-19. Butyrate also activates the transcription factor B lymphocyte-induced maturation protein-1 (BLIMP-1) and enhances the production of anti-inflammatory cytokines.