Deciphering the role of 12/15-lipoxygenase in asthma: insights into mitochondrial dysfunction and therapeutic implications

Abstract

This review delves into the complex role of 12/15-lipoxygenase (12/15-LOX) in asthma pathogenesis, focusing on its contributions to mitochondrial dysfunction, oxidative stress, epithelial injury, and airway remodeling. We provide new insights into potential therapeutic strategies aimed at improving asthma management. Additionally, we examine the pro-inflammatory functions of interleukin-4 (IL-4) and its regulatory mechanisms that upregulate 12/15-LOX, leading to increased oxidative stress and airway remodeling. Key interventions such as vitamin E, esculetin, and baicalein are highlighted for their potential to inhibit 12/15-LOX activity, reduce oxidative stress, and restore mitochondrial function. Vitamin E suppresses IL-4 transcription, reducing 12/15-LOX expression and its inflammatory metabolites, while esculetin and baicalein directly inhibit 12/15-LOX, mitigating inflammation and oxidative damage. These antioxidants also promote mitochondrial biogenesis, protect mitochondrial DNA, and enhance respiratory efficiency, contributing to improved cellular metabolism and reduced apoptosis. This comprehensive approach emphasizes the therapeutic potential of targeting 12/15-LOX pathways to alleviate asthma symptoms and improve patient outcomes, paving the way for novel treatment strategies that significantly enhance asthma therapy.

Keywords

12/15-Lipoxygenase / mitochondrial dysfunction / asthma / antioxidants / vitamin E / esculetin / baicalein

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