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


AIM OF THE STUDY
To provide experimental data supporting clinical adaptation of total indole alkaloids ( TA) from A. scholaris leaves for treating emphysema.


MATERIALS AND METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
['Zhao|Yun-Li|YL|', 'Yang|Zi-Feng|ZF|', 'Wu|Bai-Fen|BF|', 'Shang|Jian-Hua|JH|', 'Liu|Ya-Ping|YP|', 'Wang|Xin-Hua|XH|', 'Luo|Xiao-Dong|XD|']
D031051:Alstonia D000818:Animals D000893:Anti-Inflammatory Agents D017209:Apoptosis D016207:Cytokines D004195:Disease Models, Animal D004549:Elastin D005353:Fibronectins D026121:Indole Alkaloids D018836:Inflammation Mediators D008168:Lung D008297:Male D053508:Matrix Metalloproteinase 12 D008813:Mice, Inbred ICR D010100:Oxygen D018515:Plant Leaves D011656:Pulmonary Emphysema D015398:Signal Transduction D016212:Transforming Growth Factor beta D042461:Vascular Endothelial Growth Factor A
Indole alkaloids Pulmonary emphysema Inflammation Alstonia scholaris leaf Apoptosis Protease/antiproteinase balance