Anti-inflammatory action of Cecropia pachystachya in the treatment of COPD and in silico study of the target enzymes of chronic respiratory diseases 5-LOX and α-1-antitrypsin

Cecropia pachystachya Tréc. is used by the ethnic population for the treatment of asthma, hypertension, inflammation, bronchodilator effect. This study aimed to identify the chemical compounds present in the ethanolic extract of the leaves of C. pachystachya and to verify its therapeutic action in the treatment of chronic pulmonary disease. The extract was prepared with 99% ethanol and the compounds were identified by HPLC. The phytochemical compounds were submitted to in silico tests of ADMET prediction and molecular docking with the target enzymes of chronic respiratory diseases (5-LOX and α-1-antitrypsin). The in vivo COPD induction test was carried out in wistar rats, exposed to cigarette smoke to induce inflammation and destruction of alveoli, being treated with ethanolic extract of C. pachystachya leaves and with a combination of beclomethasone dipropionate. By HPLC, the compounds chlorogenic acid (01), catechin (02) and coumaric acid (03) were identified. The ADMET properties were determined for each molecule, and all fall within the parameters of the rule of five and can be classified as drugs. Among the molecular docking calculations, the complexes with catechin showed better interaction energy values with the 5-LOX enzyme and α-1-antitrypsin. The ethanolic extract of C. pachystachya leaves was able to reduce lung inflammation and attenuate the destruction of lung alveoli, showing better results when used alone than when associated with beclomethasone dipropionate. It is evident that C. pachystachya has therapeutic action due to the presence of catechin. These results have scientific relevance and justify further studies to identify the mechanisms of action of this therapeutic activity.

厚穗号角树（*Cecropia pachystachya* Tréc.）被当地原住民族群用于治疗哮喘、高血压、炎症，且具备支气管扩张活性。本研究旨在鉴定厚穗号角树叶片乙醇提取物中的化学成分，并验证其在慢性肺部疾病治疗中的应用价值。该提取物以99%乙醇制备，采用高效液相色谱法（High Performance Liquid Chromatography，HPLC）对其中的化合物进行定性鉴定。对提取得到的植物化学成分开展了计算机模拟（in silico）ADMET（吸收、分布、代谢、排泄与毒性）预测及分子对接测试，对接靶点为慢性呼吸系统疾病相关的5-脂氧合酶（5-LOX）和α-1-抗胰蛋白酶（α-1-antitrypsin）。体内慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease，COPD）诱导实验以Wistar大鼠为实验对象，通过香烟烟雾暴露诱导肺部炎症与肺泡破坏，随后将造模大鼠分别给予厚穗号角树叶片乙醇提取物单一治疗，以及丙酸倍氯米松联合提取物的联合干预。经HPLC检测，共鉴定出绿原酸（编号01）、儿茶素（编号02）及香豆酸（编号03）三种化合物。对各化合物的ADMET性质进行测定，结果显示所有分子均符合类药五规则（rule of five）参数，可归类为类药候选化合物。分子对接计算结果表明，儿茶素与5-脂氧合酶、α-1-抗胰蛋白酶的结合能表现更优。厚穗号角树叶片乙醇提取物可有效减轻肺部炎症、缓解肺泡破坏，且单一给药时的治疗效果优于与丙酸倍氯米松联合给药的组别。研究证实，厚穗号角树的治疗活性源于其所含的儿茶素成分。本研究结果具备一定的科学研究价值，可为进一步阐明该治疗活性的具体作用机制提供依据，后续相关研究值得深入开展。