Unraveling the therapeutic potential of luteolin in renal pathology: a comprehensive pathway oriented approach.

Kidney diseases, particularly chronic kidney disease (CKD), represent a significant global health challenge, affecting over 9.5% of the world’s population. Both systemic inflammation and oxidative stress are strongly associated with the development of CKD and contribute to the emergence of numerous complications. Renal injury is driven by interconnected molecular pathways that collectively exacerbate inflammation, oxidative stress, and fibrotic responses. The activation of mitogen-activated protein kinase (MAPK)/nuclear factor kappa-B (NF-κB) signaling cascades, along with NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly, synergistically amplifies the inflammatory response. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) promotes excessive generation of reactive oxygen species (ROS), whereas impairment of sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf-2) signaling weakens antioxidant defenses; together, these mechanisms exacerbate oxidative stress. In addition to oxidative stress, hyperglycemia also exacerbates renal damage by activating the transforming growth factor-beta (TGF-β)/hypoxia-inducible factor-1 alpha (HIF-1α) signaling axis, thereby promoting renal fibrosis. Collectively, these events culminate in progressive renal dysfunction. In addition to conventional therapies involving anti-inflammatory and antioxidant agents, emerging studies highlight the therapeutic potential of plant-derived agents in mitigating these pathological disturbances. Luteolin is a naturally occurring flavonoid abundantly distributed in a variety of dietary and medicinal plants, such as parsley, celery, green pepper, and carrots. It is predominantly found in members of the Lamiaceae, Asteraceae, Apiaceae, Fabaceae, and Poaceae families. Several studies highlight luteolin’s potential in alleviating renal diseases by targeting key mediators, including NF-κB, NLRP3, MAPK, NOX4, ROS, SIRT1, TGF-β, cytokines, and antioxidants, among others. Thus, considering the broad therapeutic potential of luteolin and the complex pathophysiology of renal diseases, the present study aims to elucidate the mechanisms through which luteolin mitigates renal injury.