Emerging Roles of CYP450, Nrf2, and NF-κB in Multisystem Chronic Diseases

Mpora Kakwanzi Evelyn

Department of Pharmacognosy Kampala International University Uganda

Email: evelyne.mpora@studwc.kiu.ac.ug

                                                                                ABSTRACT
Cytochrome P450 enzymes (CYP450), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-κB (NF-κB) have long been studied individually in toxicology, oxidative stress, and immune activation. Emerging evidence now positions these molecules as central, interacting regulators of multisystem chronic diseases that span metabolic disorders, cardiovascular dysfunction, autoimmune conditions, neurodegeneration, and cancer. CYP450 enzymes govern the metabolism of endogenous and exogenous compounds, generating metabolites that influence redox balance and immune signaling. Nrf2 orchestrates antioxidant and cytoprotective responses, mitigating damage from reactive oxygen species (ROS) and environmental stressors. NF-κB integrates inflammatory and stress signals to regulate immune responses and cell survival. Cross-talk among these pathways shapes cellular homeostasis: CYP450-derived reactive metabolites and ROS can activate or suppress Nrf2 and NF-κB; Nrf2 influences expression of metabolic enzymes and dampens NF-κB-mediated inflammation; NF-κB modifies
expression of CYP450 genes and interacts with redox sensors. Dysregulation across this network contributes to chronic inflammation, impaired detoxification, oxidative damage, and maladaptive remodeling in multiple organ systems. This review synthesizes current knowledge on the interplay of CYP450, Nrf2, and NF-κB, highlights mechanistic insights into disease pathogenesis, and discusses therapeutic opportunities aimed at modulating these interconnected pathways.

Keywords: CYP450; Nrf2; NF-κB; oxidative stress; chronic inflammation.

CITE AS: Mpora Kakwanzi Evelyn (2026). Emerging Roles of CYP450, Nrf2, and NF κB in Multisystem Chronic Diseases. IDOSR JOURNAL OF APPLIED SCIENCES 11(2):42-47.
https://doi.org/10.59298/IDOSRJAS/2026/1124247