Kaempferol for the treatment of asthma: A review of pre-clinical evidence on therapeutic potential and mechanism

Abstract

Asthma remains a significant global health burden characterised by high clinical heterogeneity and immunological complexity. Despite currently available therapies, limitations like steroid insensitivity and adverse side effects persist. Furthermore, recent biologics' high costs and accessibility remain a constraint. This emphasised the need for innovative alternative treatments. Kaempferol, a naturally occurring flavanol found in various fruits, vegetables, and medicinal plants, has gained considerable attention for its multifaceted pharmacological properties. This review critically assesses existing preclinical evidence regarding the therapeutic potential and molecular mechanisms of kaempferol in experimental asthma models. Preclinical in vivo and in vitro studies consistently demonstrate that kaempferol targets three critical dimensions of asthma pathogenesis: airway inflammation, hyperresponsiveness, and airway remodelling. Mechanistically, it suppresses the infiltration of inflammatory cells and reduces the secretion of pro-inflammatory cytokines, chemokines, and IgE. These effects are achieved by modulating key signalling pathways, including NF-κB, MAPKs, JAK/STAT, Nrf2, and NOX4-mediated autophagy. Furthermore, kaempferol alleviates smooth muscle hypercontractility and suppresses airway remodelling by mitigating subepithelial fibrosis, mucus hypersecretion, and epithelial-to-mesenchymal transition. Its translational strengths include potential steroid-sparing effects. Despite this, its clinical application is hindered by poor oral bioavailability and a lack of direct human trials. Rigorous clinical validation and advanced targeted delivery systems are required to establish kaempferol as a viable therapeutic agent for asthma management.