Indole alkaloids from leaves of Alstonia scholaris (L.) R. Br. protect against emphysema in mice.

Alstonia scholaris (L.) R. Br. (Apocynaceae) is a medicinal plant in China traditionally used to treat pulmonary diseases, including bronchitis, whooping cough, asthma and chronic obstructive pulmonary disease.To provide experimental data supporting clinical adaptation of total indole alkaloids ( TA) from A. scholaris leaves for treating emphysema.An emphysema model was induced by a single intratracheal instillation of porcine pancreatic elastase followed by administration of TA and four main alkaloid components (scholaricine, 19-epischolaricine, vallesamine, and picrinine) for 30 consecutive days. Cytokine levels, histopathological parameters and protein expression in lung tissues were examined.Administering the TA, picrinine, scholaricine, 19-epischolaricine and vallesamine for 30 days effectively inhibited inflammatory cell accumulation and invasion in the lung tissue and relieved pulmonary tissue injury. Oxygen saturation was enhanced, and interleukin (IL)-1β, monocyte-chemo attractive peptide 1, IL-11, matrix metalloproteinase-12, transforming growth factor-β and vascular endothelial growth factor levels were significantly reduced, likely by suppressing overactivation of alveolar macrophages and pulmonary fibrosis. The elastin content was markedly elevated, and fibronectin was reduced. Bcl-2 expression was significantly increased, and nuclear factor-κB and β-catenin levels were decreased.TA can be potentially used as an effective novel drug for pulmonary emphysema and exerts its effects through not only inhibiting inflammation of the airway wall and airflow resistance but also promoting lung elastic recoil and protease/anti-protease balance.