Network pharmacology-integrated molecular docking and experimental validation: Unveiling the protective mechanism of sanhuang guben zhike formula in chronic obstructive pulmonary disease

COPD—more than just tobacco smoke

Hesperetin (HE), a natural flavonoid exhibiting anti-inflammatory and antioxidant properties, holds significant potential in treating chronic obstructive pulmonary disease (COPD). Nonetheless, the precise mechanisms underlying its effects are yet to be fully elucidated. In this study, we aim to explore the role and potential mechanism of HE in treating COPD using network pharmacology, molecular docking and experimental validation. We screened for HE and COPD-related targets from public databases, and then imported potential targets into a STRING database to establish a protein–protein interaction network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes enrichment analysis were performed to obtain key signaling pathways. We then predicted the binding interactions between HE and core targets using molecular docking. The animal model of COPD was established through lipopolysaccharide and cigarette smoke induction in mice to observe lung function, inflammatory factors, pathology, and the expression of related proteins. Network pharmacology findings unveiled that HE and COPD shared 105 common targets. MAPKs and NF-κB signaling pathways were selected for further validation. In animal experiment, HE enhanced lung function and histopathological morphology, while reducing inflammation levels. The results of Western blot tests indicated that HE treatment considerably inhibited the expression of MAPKs and NF-κB. HE effectively reduced lung inflammation and improved lung function in mice. This mechanism may be achieved by inhibition of MAPKs and NF-κB signaling pathways.

Background Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high morbidity and mortality. The conventional therapies remain palliative and have various undesired effects. Shenmai injection (SMI) has shown positive effects on COPD, but its molecular mechanisms are still unclear. This study aims to investigate the bioactive ingredients and underlying mechanisms of SMI in treating COPD based on network pharmacology analysis and molecular docking validation. Methods Active ingredients in SMI were sourced from the TCMSP, SymMap, and BATMAN-TCM databases, with their targets predicted using Swiss target prediction. Potential COPD targets were obtained from the GeneCards, OMIM and GEO databases. Cytoscape software was employed to construct the candidate component-target network for SMI in treating COPD. Furthermore, the functions and signaling pathways of shared targets between SMI and COPD were enriched by GO and KEGG analyses. Finally, molecular docking studies of key active ingredients and hub targets were performed using Autodock vina software. Results A total of 28 active components were identified, corresponding to 606 targets, including 341 common targets shared by the active components and COPD. The top 10 hub targets were screened, namely STAT3, SRC, EGFR, HSP90AA1, AKT1, IL6, TNF, BCL2, JUN and CCND1. GO enrichment analysis yielded 127 entries for biological processes (BP), 32 for cellular components (CC), and 33 for molecular functions (MF). The significantly enriched iterms in BP, CC, and MF enrichment were associated with response to xenobiotic stimulus, plasma membrane, and protein serine/threonine/tyrosine kinase activity, respectively. KEGG enrichment analysis identified 189 significantly enriched pathways, primarily including pathways in cancer, PI3K-Akt signaling pathway and chemical carcinogenesis- receptor activation. These pathways play roles in the effect of SMI on treating COPD. Molecular docking results demonstrated the effective binding of the primary active ingredients (Ophiopogonanone A, Ruscogenin, Stigmasterol) to their respective targets (EGFR, AKT1, HSP90AA1). Conclusion SMI treats COPD through a multi-component, multi-target, and multi-pathway synergistic network, providing a basis for further exploration of SMI's mechanisms in COPD treatment.

Maintenance pharmacotherapy of mild and moderate COPD: What is the Evidence?

Introduction

Do we really need asthma–chronic obstructive pulmonary disease overlap syndrome?

UK COPD treatment: failing to progress

Management of chronic obstructive pulmonary disease: Moving beyond the asthma algorithm

Chronic obstructive pulmonary disease (COPD) is an important differential diagnosis in patients with heart failure (HF). The primary aims were to determine the prevalence of COPD and to test the accuracy of self-reported COPD in patients admitted with HF. Secondary aims were to study a possible relationship between right and left ventricular function and pulmonary function. Prospective substudy. Systematic screening at 11 centres. Consecutive patients (n = 532) admitted with HF requiring medical treatment with diuretics and an episode with symptoms corresponding to New York Heart Association class III-IV within a month prior to admission. Forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) were measured by spirometry and ventricular function by echocardiography. The diagnosis of COPD and HF were made according to established criteria. The prevalence of COPD was 35%. Only 43% of the patients with COPD had self-reported COPD and one-third of patients with self-reported COPD did not have COPD based on spirometry. The prevalence of COPD in patients with preserved left ventricular ejection fraction (i.e. LVEF >or=45%) was significantly higher than in patients with impaired LVEF (41% vs. 31%, P = 0.03). FEV(1) and FVC were negatively correlated with right ventricular end-diastolic diameter and tricuspid annular plane systolic excursion and FVC positively correlated with systolic gradient across the tricuspid valve. Chronic obstructive pulmonary disease is frequent in patients admitted with HF and self-reported COPD only identifies a minority. The prevalence of COPD was high in both patients with systolic and nonsystolic HF.

Klaus Rabe: incoming President of the ERS

Towards better management of COPD

Objective To explore the mechanism of action of Bu-Fei-Yi-Shen formula (BFYSF) in treating chronic obstructive pulmonary disease (COPD) based on network pharmacology analysis and molecular docking validation. Methods First of all, the pharmacologically active ingredients and corresponding targets in BFYSF were mined by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the analysis platform, and literature review. Subsequently, the COPD-related targets (including the pathogenic targets and known therapeutic targets) were identified through the TTD, CTD, DisGeNet, and GeneCards databases. Thereafter, Cytoscape was employed to construct the candidate component-target network of BFYSF in the treatment of COPD. Moreover, the cytoHubba plug-in was utilized to calculate the topological parameters of nodes in the network; then, the core components and core targets of BFYSF in the treatment of COPD were extracted according to the degree value (greater than or equal to the median degree values for all nodes in the network) to construct the core network. Further, the Autodock vina software was adopted for molecular docking study on the core active ingredients and core targets, so as to verify the above-mentioned network pharmacology analysis results. Finally, the Omicshare database was applied in enrichment analysis of the biological functions of core targets and the involved signaling pathways. Results In the core component-target network of BFYSF in treating COPD, there were 30 active ingredients and 37 core targets. Enrichment analysis suggested that these 37 core targets were mainly involved in the regulation of biological functions, such as response to biological and chemical stimuli, multiple cellular life processes, immunity, and metabolism. Besides, multiple pathways, including IL-17, Toll-like receptor (TLR), TNF, and HIF-1, played certain roles in the effect of BFYSF on treating COPD. Conclusion BFYSF can treat COPD through the multicomponent, multitarget, and multipathway synergistic network, which provides basic data for intensively exploring the mechanism of action of BFYSF in treating COPD.

The silent epidemic of COPD in Africa.

On account of the long-term inflammatory microenvironment, diabetic wounds are challenging to heal in which advanced glycation end products are considered important factors hindering the healing of diabetic wounds. Gum Arabic has demonstrated significant potential in the treatment of various diseases owing to its anti-inflammatory and antioxidant properties. Nonetheless, there is still insufficient research on the role of Arabic gum in facilitating diabetic wounds healing and its mechanisms. This study aims to investigate the pharmacological targets and therapeutic mechanisms of Arabic Gum on diabetic wound healing by adopting network pharmacology, molecular docking, and experimental validation. Key active components of Arabic Gum and disease targets were identified through network pharmacology and bioinformatics. GO/KEGG enrichment was performed to identify critical pathways. Cytoscape and AutoDock were used for targets prediction and molecular docking validation. In vitro, Transwell assay and tube formation assay were performed to evaluate the effect of Arabic Gum on human fibroblasts migration and human umbilical vein endothelial cells angiogenesis. Western blotting analyzed Pro-caspase-1, ASC, NLRP3 and NF-κB pathway-related proteins. In vivo, a full-thickness diabetic wound model was established. Histological changes were assessed via H&E and Masson's staining, oxidative stress levels through DHE staining, inflammation levels with IL-1β, CD68 and CD206 staining, angiogenesis and cell proliferation levels were assessed by CD31 and Ki67 staining. The levels of pathway-related proteins were analyzed by NLRP3 and Phospho-NF-κB P65 staining. Network pharmacology analysis identified key targets, encompassing HSP90AA1, STAT3, and PRKCB, involved in the AGEs-NF-κB-NLRP3 signaling axis. Molecular docking demonstrated strong binding affinity between AG components and these targets. In vitro, AG lessened AGEs-induced activation of the NLRP3 inflammasome via modulation of the NF-κB pathway and reinforced cell migration and angiogenesis. In vivo, AG-treated diabetic wounds exhibited accelerated healing, with augmented collagen deposition, lowered oxidative stress and inflammation, and strengthened cell migration and angiogenesis. AG promotes diabetic wound healing by modulating the AGEs-NF-κB-NLRP3 axis, exerting anti-inflammatory, antioxidant, pro-angiogenic, and cell-proliferative effects. This study provides new insights into diabetic wound repair and suggests that AG is a promising therapeutic agent for improving diabetic wound healing.

Cause-specific mortality adjudication in the UPLIFT® COPD trial: Findings and recommendations