Curcumin in ischemia–reperfusion injury across multiple organs: A review

Abstract

Ischemia–reperfusion injury is a secondary pathophysiological process triggered by the restoration of blood flow to ischemic tissues, characterized by a detrimental cascade of oxidative stress, hyperinflammation, and programmed cell death that frequently compromises the function of multiple vital organs, including the heart, brain, liver, and kidneys. This narrative review systematically synthesizes current evidence on the protective efficacy and molecular mechanisms of curcumin, a natural polyphenolic compound, against ischemia–reperfusion injury across major organ systems. Mechanistically, curcumin orchestrates a multitargeted defense by activating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 antioxidant axis, suppressing the nuclear factor kappa-light-chain-enhancer of activated B cells-driven inflammatory storm, and modulating the phosphoinositide 3-kinase/protein kinase B survival pathway. These actions collectively result in the inhibition of reactive oxygen species generation, mitigation of mitochondria-dependent apoptosis, and preservation of microcirculatory integrity. Although curcumin demonstrates significant protective effects across the heart, liver, kidneys, lungs, brain, spinal cord, and intestines by reducing tissue damage markers and ameliorating pathological morphology, its clinical translation remains hindered by the inherent drawbacks of poor water solubility, low oral bioavailability, and rapid metabolic clearance. Future research should prioritize the integration of curcumin with advanced nanocarrier delivery systems and high-resolution spatial transcriptomics to enhance targeted therapeutic efficacy, thereby paving the way for novel clinical strategies against ischemia–reperfusion injury.