Polydatin in respiratory diseases: multi-target mechanisms and therapeutic potential

Respiratory diseases constitute a heterogeneous group of disorders that primarily involve the lungs. Driven by worsening air pollution, tobacco use, occupational exposures, the COVID-19 pandemic, and population aging, they show persistently high incidence with rising mortality and disability, posing a major global public-health challenge. Current pharmacotherapies-principally antibiotics, glucocorticoids, β₂-adrenoceptor agonists, and antiviral agents-yield only limited benefit and are constrained by adverse reactions such as gastrointestinal disturbances and hepatorenal toxicity, alongside the escalating problem of drug resistance. The development of safer and more effective therapeutics is therefore of considerable clinical and socioeconomic importance. Plant-derived natural products have attracted increasing interest in the management of respiratory diseases. Polydatin (resveratrol-3-O-β-D-glucoside; also known as piceid; PD) is a stilbenoid polyphenol of plant origin that is widely distributed in Polygonum cuspidatum (Japanese knotweed), Polygonum multiflorum, grapes, peanuts, mulberries, blueberries, and rhubarb. Accumulating evidence indicates that PD exerts anti-inflammatory, antioxidant, antimicrobial, immunomodulatory, and metabolic-regulatory activities and shows potential therapeutic value in pulmonary fibrosis, acute lung injury/acute respiratory distress syndrome, pneumonia, lung cancer, and asthma. This review provides a comprehensive synthesis of the multi-target and multi-pathway mechanisms by which PD acts against respiratory diseases, offering a mechanistic rationale and evidence base to support its clinical development.