Saffron and its Bioactive Constituents as Mitochondria-Targeted Protectors Against Organ Injury

Mitochondria are central regulators of cellular homeostasis, controlling energy production, redox balance, and programmed cell death. Their dysfunction is a major contributor to oxidative stress, inflammation, and organ injury across a wide spectrum of diseases. Natural products with multi-targeted properties have gained increasing attention as mitochondria-protective agents. Among them, saffron (Crocus sativus L.) and its principal constituents crocin, crocetin, safranal, and the synthetic derivative trans-sodium crocinate (TSC) exhibit potent antioxidant, anti-inflammatory, and cytoprotective activities. Evidence from in vitro and in vivo studies indicates that these compounds reduce reactive oxygen species (ROS) generation, stabilize mitochondrial membrane potential (MMP), and modulate cell death pathways, including the intrinsic mitochondrial pathway and parthanatos. They also enhance mitochondrial biogenesis and dynamics via mechanisms involving Drp1/Fis1, MFN, SIRT3, PGC-1α, and related signaling cascades. Overall, current experimental evidence suggests that saffron and its derivatives may represent promising adjunctive candidates for the prevention and mitigation of organ injury associated with mitochondrial dysfunction. However, further clinical studies are required to validate their therapeutic efficacy and safety in human subjects.