Effects And Mechanisms Of Bufei Huoxue Capsules In Treating COPD In Rats

Background Chronic Obstructive Pulmonary Disease is a common,preventable,and treatable disease characterized by continuous and progressive airflow limitation.COPD was the third leading chronic disease after hypertension and diabetes and It was estimated that nearly 100 million people are suffering from COPD in China,presenting.However,there is still lack of effective drugs or measures to prevent its progression.Glucocorticoid and bronchodilator,the first-line drugs for COPD,only improve symptoms of the patient,but have little effect on the pathological changes of the disease.Therefore,it is urgent to find a drug for the pathogenesis of COPD.Bufei Huoxue?BFHX?,a traditional Chinese medicine,have been applied in China for thousands of years,containing three common Chinese herbals-including Astragalus,Radix paeoniae rubra,and Psoralea corylifolia.Astragalus has the effect of tonifying qi,raising Yang,diuresis and detumescence,and radix paeoniae rubra has the effect of promoting blood circulation and removing blood stasis,and Psoralea corylifolia has the effect of warming kidney,helping Yang.Combination of the three herbals can invigorate qi and blood,strengthen lung and kidney,and it is thus commonly used in the treatment of patients with pulmonary heart disease.However,systematic evidence-based medicine for the treatment of COPD is still lacking,and its pharmacological mechanism is not clear.Objectives To evaluate the therapeutic effect of BFHX capsules on COPD and investigate its potential targets and mechanism.Methods The study was divided into three parts:1.Animal experiment:A rat model of COPD was established by cigarette smoking?CS?exposure with LPS instillation;The total exposure time was 110 days and LPS was administered intratracheally on the 1^st,14^th day respectively.BFHX capsules was gavage from 81^stt until the end.At the end of the CS exposure,all animals were subjected to lung function analysis.Then the BALF will be collected for cell counting and stanning.Finally,the left lung tissue was perfused with 10%neutral formalin then made into paraffin sections for tissue staining including H&E,MASSON and PAS.2.Network pharmacology:Firstly,we identified the active components and molecular targets of the three herbals in BFHX capsules from TCMSP platforms and BATMAN-TCM database.And the pharmaceutical molecular-target network was constructed by cytoscape3.2.1 software.Secondly,targets related to COPD were searched by TTD,GeneCards,OMIM and polysearch2 database with the key word“COPD or chronic obstructive pulmonary disease”.Next,all targets were standardized by Uniprot database to obtain standard gene name,the intersection of BFHX and COPD extracted by venny2.1 software.Finally,the gene in the intersection was analyzed by Bioconductor bioinformatic packages for GO biological process and KEGG pathway enrichment analysis.3.The potential therapeutic target of BFHX capsules for COPD was verified by western blotting and tunnel staining.Results 1.Effects of BFHX Capsules on lung function in CS-induced COPD rats.Compared with the normal control group,there was a significant increase in functional residual capacity?FRC?and a significant decrease in FEV20/FVC%in the model control group,which was significantly improved by BFHX capsules.2.Effects of BFHX Capsules on lung Histopathology in CS-induced COPD rats.HE:compared with the normal control group,the structurally disordered and damaged alveolar wall and fused pulmonary bulla were observed in the model group.In addition,a large number of inflammatory cells were observed in the alveolar cavity and septum in the model group.All these pathological changes were significantly alleviated after the treatment with BFHX capsules.PAS:Compared with the normal control group,metaplasia of airway goblet cells was evident in model group,and it was improved after the treatment with BFHX capsules.MASSON:Compared with the normal control group,collagen deposition in the airways was significantly increased in the model group,which was reduced after the treatment with BFHX capsules.3.Effects of BFHX Capsules on total cell count and classification in BALF in CS-induced COPD rats compared with the normal control group,leukocyte and macrophage was significantly increased in model control group,which was decreased after the treatment with BFHX capsules.4.Effects of BFHX Capsules on cytokines in BALF in CS-induced COPD rats Compared with the normal control group,IL-1?,IL-6 and KC in BALF was significantly increased in model group,which was significantly reduced after the treatment with BFHX capsules.5.Network pharmacology analysis of BFHX Capsules for COPD Sixty-one actives and 631 targets were found in BFHX capsules,and 639 targets were related to COPD.Finally,65 targets were obtained in the intersection of BFHX Capsules and COPD.A total of 115 GO term and 127 KEGG pathway were acquired by enrichment analysis,such as cAMP signaling,PI3K-Akt signaling,and HIF-1 signaling.Conclusion BFHX Capsules has a significant therapeutic effect on COPD rats,and its mechanism may be related to inhibiting lung inflammation,improving pathologic changes in lung and airway,and inhibiting apoptosis in lung.