Nuclear factor erythroid 2–related factor 2 signaling pathway and Nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway (Nrf2/HO-1 and NF-κB signaling pathways)

The Nrf2/HO-1 and NF-κB signaling pathways are interconnected molecular cascades central to cellular responses against oxidative stress and inflammation. **Nrf2** is a transcription factor regulating antioxidant defense by inducing genes like **HO-1**; under oxidative stress, it translocates to the nucleus and activates the antioxidant response element (ARE). **HO-1** is an anti-inflammatory enzyme produced in response to Nrf2 activation and suppresses pro-inflammatory signaling by degrading heme and producing cytoprotective molecules. **NF-κB** mediates inflammatory gene expression and is activated by reactive oxygen species (ROS) and cellular injury. These pathways exhibit *bidirectional crosstalk*; Nrf2 activation limits NF-κB-driven inflammation by suppressing ROS and stabilizing IκB-α, while NF-κB can modulate Nrf2 activity directly and indirectly. Disruption in their balance underlies many chronic diseases—from cancer and neurodegeneration to metabolic and autoimmune disorders. Pharmacologically, both pathways are therapeutic targets, with drugs and natural compounds aiming to activate Nrf2/HO-1 or inhibit NF-κB to restore redox and immune homeostasis.

Other names

Nrf2 pathwayKeap1-Nrf2-ARE pathwayNF-κB pathwayNrf2/Keap1 signalingNrf2–HO-1 axis

Activation of Nrf2: induces transcription of ARE-regulated antioxidant and cytoprotective genes, including HO-1; suppresses oxidative stress; inhibits pro-inflammatory signaling through reduction of ROS and direct suppression of NF-κB; Inhibition of NF-κB: suppresses transcription of inflammatory cytokines/mediators (e.g., TNF-α, IL-1β, IL-6, iNOS); Upregulation of HO-1: provides anti-inflammatory and cytoprotective effects via heme breakdown and end-products (CO, bilirubin)