Tanshinone IIA protects against chronic obstructive pulmonary disease via exosome‑shuttled miR‑486‑5p

Chronic obstructive pulmonary disease (COPD) is one of the major causes of death worldwide today, and its related morbidity has been predicted to show an increase in subsequent years. Recent studies have shown that Danshen, a Chinese herbal medicine, is a potential drug in the treatment of inflammation‑related lung diseases. COPD was induced in this study using cigarette smoke (CS) exposure plus intranasal inhalation of lipopolysaccharide to ascertain whether the main pharmacological component from Danshen, tanshinone IIA (TIIA), and its water soluble form, sodium tanshinone IIA sulfonate (STS), protect against the development of COPD. The weight, lung function, hematoxylin and eosin staining, and Masson Trichrome determinations revealed that TIIA inhalation attenuated lung dysfunction in COPD mice induced by cigarette smoke and lipopolysaccharide exposure. In addition, exosomes derived from TIIA‑treated COPD mice exerted similar protective effects against COPD, suggesting that TIIA may protect against COPD through exosome‑shuttled signals. miR‑486‑5p was found to be a key molecule in mediating the protective effects of exosomes derived from TIIA‑treated COPD mice using miRNA sequencing and cellular screening. Treatment of COPD mice with an agomiR of miR‑486‑5p protected lung function in COPD mice, and treatment of COPD mice with an antagomir of miR‑486‑5p abolished the protective effects of TIIA. Moreover, luciferase activity reporter assay, RT‑qPCR, and western blot analyses showed that miR‑486‑5p exerted protective effects against COPD via targeting phosphoinositide‑3‑kinase regulatory subunit 1 (PIK3R1). These results suggest that STS protects against COPD through upregulation of miR‑486‑5p, and that TIIA or miR‑486‑5p is a potential drug for the treatment of COPD.