Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, PR China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, PR China.
Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming, 650500, PR China.
J Ethnopharmacol. 2021 Mar 1;267:113506. doi: 10.1016/j.jep.2020.113506. Epub 2020 Oct 22.
Alstonia scholaris (L.) R. Br. (Apocynaceae) is a Dai folk medicine for the treatment of lung diseases in China.
The present study investigated the anti-pulmonary fibrosis effects of total alkaloids (TA) and the potential active ingredients and its possible mechanism.
After intratracheal instillation of bleomycin (BLM, 5 mg/kg), mice were divided into ten groups, and orally treated with the corresponding samples once daily for 28 days. The effect of indole alkaloids was determined through analysis of cytokines, as well as histopathological examinations and gene expressions.
Severe lung fibrosis was observed in the BLM-treated mice on day 28. However, the administration of TA significantly ameliorated the pathological changes in the lungs, decreased the content of Krebs von den Lungen-6, lactate dehydrogenase, transforming growth factor-β (TGF-β), hydroxyproline, type I collagen, and malonaldehyde, and enhanced the activity of superoxide dismutase in the serum and lung tissues. In addition, the enhanced TGF-β and matrix metalloproteinase-1 (MMP-1) expressions in BLM-induced mice were obviously weakened by indole alkaloids, as well as the ratio of matrix metalloproteinase-1 to tissue inhibitor of metalloproteinase-1 was decreased. Moreover, picrinine and scholaricine yielded markedly better values in the aforementioned indices than those in other samples, indicating that they may be the active ingredients of alkaloids.
TA exerted protective effects against BLM-induced pulmonary fibrosis by reducing collagen deposition through TGF-β/MMP-1 pathway.
垂珠树（Alstonia scholaris（L.）R. Br.）（夹竹桃科）是中国傣族民间医学用于治疗肺部疾病的药物。
本研究旨在探讨总生物碱（TA）及其潜在活性成分的抗肺纤维化作用及其可能的机制。
博来霉素（BLM，5mg/kg）气管内滴注后，将小鼠分为十组，每天口服相应样品一次，共 28 天。通过分析细胞因子、组织病理学检查和基因表达来确定吲哚生物碱的作用。
第 28 天，BLM 处理的小鼠出现严重的肺纤维化。然而，TA 的给药显著改善了肺部的病理变化，降低了 Krebs von den Lungen-6、乳酸脱氢酶、转化生长因子-β（TGF-β）、羟脯氨酸、I 型胶原和丙二醛的含量，并增强了血清和肺组织中超氧化物歧化酶的活性。此外，吲哚生物碱明显减弱了 BLM 诱导的小鼠 TGF-β和基质金属蛋白酶-1（MMP-1）表达的增强，以及基质金属蛋白酶-1与组织抑制剂金属蛋白酶-1的比值降低。此外，小檗碱和垂珠宁在上述指标中的值明显优于其他样品，表明它们可能是生物碱的活性成分。
TA 通过 TGF-β/MMP-1 通路减少胶原蛋白沉积，对 BLM 诱导的肺纤维化发挥保护作用。
