Oxidative Stress Driven Airway Mesenchymal Reprogramming in Asthma: Mechanistic Insights and Evidence from Botanical Drug Formulations

Abstract

Asthma-associated airway mesenchymal reprogramming refers to a dynamic pathological process characterized by persistent pathological alterations in phenotype, function, and intercellular interactions of airway mesenchymal cells under asthmatic conditions, which actively drive airway structural changes, airway narrowing, and impaired lung function. It is considered one of the key pathological mechanisms driving the chronic progression of asthma and contributing to persistent airflow limitation. Oxidative stress, as a central pathogenic factor, drives asthma-associated airway mesenchymal reprogramming through multiple mechanisms, including promoting inflammation, inducing epithelial-to-mesenchymal transition (EMT), exacerbating airway smooth muscle dysfunction, and impairing endogenous antioxidant defense systems. Increasing evidence suggests that this reprogramming may initiate at early stages of asthma, highlighting its potential relevance as an early pathogenic indicator. Although standard therapies such as inhaled corticosteroids and β₂-agonists are effective in controlling acute inflammation, they show limited efficacy in effectively modulating or substantially improving established mesenchymal reprogramming. Traditional Chinese Medicine (TCM), with its long history of use in asthma, offers a complementary therapeutic approach due to its multi-component, multi-target actions, low adverse effect profile, and anti-inflammatory, antioxidant, and modulatory effects on airway mesenchymal reprogramming. This review focuses on the potential of metabolites originating from botanical drugs used in TCM and botanical drug formulations in modulating oxidative stress to intervene in asthma-associated airway mesenchymal reprogramming, providing comprehensive evidence to support mechanistic investigation and translational research in managing this key pathological process.