Molecular insights and translational potential of ferulic acid in radiation protection

Ferulic acid, a common dietary phenolic abundant in plant cell walls, has been identified as a potential drug candidate with radiation-protective effects in experimental models. This review summarizes new developments regarding the molecular mechanisms, experimental models and translational potential of ferulic acid-induced radioprotection. Mechanistically, ferulic acid attenuates ionizing radiation-induced damage by scavenging free radicals, inhibiting lipid peroxidation, maintaining mitochondrial fitness, modulating inflammation signaling pathways and upregulating endogenous antioxidant systems partially through nuclear translocation of the Nrf2 pathway. Preclinical studies across in vitro (human and animal cell lines), ex vivo (human blood chromosomal aberration, micronucleus, and γ-H2AX assays), and in vivo rodent models consistently show that ferulic acid reduces DNA damage and chromosomal alterations, supports cell survival pathways, and, in some conditions, enhances DNA repair, translating into improved tissue histology, hematopoietic recovery, and post-irradiation survival. Despite promising efficacy signals, there are still issues with pharmacokinetics, optimal dosing schedules, long-term safety/adverse events, and bioavailability in humans. This review discusses the priority directions for translation: (1) systematic pharmacokinetic and toxicology profiling, (2) discovery of ferulic acid derivatives and delivery systems (e.g. nanoparticles, prodrugs) that facilitate tissue targeting, and (3) rigorous clinical trials in prophylactic and post-exposure settings, with combination strategies involving established radioprotectors. Bridging preclinical mechanistic insights with rigorous clinical evaluation could position ferulic acid as a safe, low-cost, and widely accessible radioprotective adjunct suitable for both medical and occupational applications.