Abstract
Danggui Buxue Decoction (DBD) as a traditional Chinese medicine compound was firstly found in "Nei Wai Shang Bian Huo Lun" for more than 700 years, which mainly composed of Astragalus and Angelica. In clinical practice, DBD is employed therapeutically for a range of respiratory conditions. However, investigations into the therapeutic mechanism of DBD against chronic obstructive pulmonary disease (COPD) remain scarce. Mitigating effect and mechanism of DBD and its bio-active compounds on COPD tracheal injury were studied using Drosophila melanogaster and SD rat models. The protective effects of DBD against cigarette smoke (CS)-induced injury in Drosophila and rats were assessed. In Drosophila, protection was evaluated using metrics including survival rate, locomotion capacity, tracheal length and thickness, and the number of nuclei in tracheal epithelial cells. In rats, lung function, histological changes in the lungs, collagen fibers, and overall inflammation levels were measured. Subsequently, the molecular mechanism of DBD was detected by transcriptome sequencing, bioinformatics, immunofluorescence, ELISA and real-time PCR. Meanwhile, liquid chromatography-mass spectrometry (LC-MS), ADME online prediction, fly larval phenotyping experiments, molecular docking and molecular dynamics simulation were utilized to further identify core active components of DBD for ameliorating COPD tracheal injury. DBD significantly extended the survival rate, increased the motility, and also restored pupal area, larval tracheal length, tracheal wall thickness, and the number of tracheal epithelial cell nuclei in flies. In COPD rats, DBD improved lung function, reduced alveolar septal thickening and inhibited the expression of inflammatory factors. Meanwhile, DBD remarkably down-regulated the gene and protein expressions in JAK1-STAT3 pathway, inhibited the tracheal ROS accumulation, increased protein expressions of glutathione metabolic pathway and GSH content. Additionally, ferulic acid, rhein, curcumin and gallic acid were found to alleviate CS-induced injury in flies, in which curcumin and rhein as the core compounds of DBD can bind stably to STAT3 and GSTT1, respectively. DBD could ameliorate COPD tracheal injury via inhibiting the JAK-STAT pathway and activating the glutathione metabolic pathway. Curcumin, and rhein are the core bioactive compounds in DBD that alleviate COPD tracheal injury.
