Herbal Polyphenolic Mixtures as Antioxidant and Cytoprotective Agents in Respiratory Diseases: Molecular Mechanisms and Therapeutic Perspectives.

Abstract

Oxidative stress is a central pathogenic mechanism in acute and chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and pulmonary fibrosis. Excessive production of reactive oxygen and nitrogen species (ROS/RNS), combined with impaired antioxidant defenses, contributes to epithelial and endothelial injury, inflammation, mitochondrial dysfunction, airway remodeling, and progressive loss of lung function. Plant-derived polyphenols and polyphenol-rich herbal mixtures have emerged as promising candidates for respiratory protection due to their multimodal activity. They exert effects through direct antioxidant action, enhancement of glutathione-dependent and enzymatic defenses, activation of the Nrf2/HO-1 pathway, and suppression of NF-κB, MAPK, inflammasome, and profibrotic signaling. Experimental studies have demonstrated protective effects of compounds such as quercetin, resveratrol, rosmarinic acid, epigallocatechin gallate, and phenolic-rich extracts. However, clinical translation remains limited by poor bioavailability, variability of botanical preparations, lack of standardization, and insufficient high-quality human studies. This review summarizes key mechanisms of oxidative lung injury and critically evaluates the therapeutic potential and translational challenges of herbal polyphenolic mixtures in respiratory diseases.