RESUMEN
Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder in pulmonology. Chuanbeimu (CBM) is a traditional Chinese medicinal herb for treating COPD and has been widely utilized in clinical practice. However, the mechanism of CBM in the treatment of COPD remains incompletely understood. This study aims to investigate the underlying therapeutic mechanism of CBM for COPD using network pharmacology and experimental approaches. Methods: Active ingredients and their targets were obtained from the Traditional Chinese Medicine Systems Pharmacology database. COPD-associated targets were retrieved from the GeneCards database. The common targets for CBM and COPD were identified through Venn diagram analysis. Protein-protein interaction (PPI) networks and disease-herb-ingredient-target networks were constructed. Subsequently, the results of the network pharmacology were validated by molecular docking and in vitro experiments. Results: Seven active ingredients and 32 potential targets for CBM were identified as closely associated with COPD. The results of the disease-herb-ingredient-target network and PPI network showed that peimisine emerged as the core ingredient, and SRC, ADRB2, MMP2, and NOS3 were the potential targets for CBM in treating COPD. Molecular docking analysis confirmed that peimisine exhibited high binding affinity with SRC, ADRB2, MMP2, and NOS3. In vitro experiments demonstrated that peimisine significantly upregulated the expression of ADRB2 and NOS3 and downregulated the expression of SRC and MMP2. Conclusion: These findings indicate that CBM may modulate the expression of SRC, ADRB2, MMP2, and NOS3, thereby exerting a protective effect against COPD.
Asunto(s)
Medicamentos Herbarios Chinos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Metaloproteinasa 2 de la Matriz , Farmacología en Red , Mapas de Interacción de Proteínas , Medicina Tradicional China , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Chronic obstructive pulmonary disorder (COPD) is a chronic respiratory disease that is a major cause of morbidity and mortality worldwide. Previous studies have shown that miR1865p expression is significantly increased in COPD and is involved in multiple physiological and pathological processes. However, the role of miRNA1865p in the inflammatory response of COPD remains unclear. In this study, an in vitro model of COPD was established using lipopolysaccharide (LPS)induced human bronchial epithelial cells (BEAS2B). CCK8 assays, flow cytometry, and a Muse cell analyzer were used to determine cell viability, cell cycle distribution, and apoptosis, respectively. The production of TNFα and IL6 were measured by ELISA. Reversetranscriptionquantitative PCR and western blotting were used to analyze mRNA and protein expression levels. The targeting relation between miR1865p and HIF1α was discovered using dualluciferase reporter assays. The results showed that transfection of miR1865p inhibitor inhibited cell proliferation and promoted cell apoptosis in the LPSinduced BEAS2B cells. Inhibition of miR1865p markedly increased the levels of TNFα and IL6. miR1865p directly targeted and negatively regulated HIF1α expression. In addition, inhibition of miR1865p increased the expression of the NFκB pathway protein pp65. In conclusion, it was found that inhibiting miR1865p may improve inflammation of COPD through HIF1α in LPSinduced BEAS2B cells, possibly by regulating NFκB signaling. These findings provide a novel potential avenue for the clinical management of COPD. Future research is required to determine the mechanism of the interaction between miR1865p and HIF1α in COPD.
Asunto(s)
MicroARNs , Enfermedad Pulmonar Obstructiva Crónica , Humanos , FN-kappa B/metabolismo , Línea Celular , Factor de Necrosis Tumoral alfa/genética , Lipopolisacáridos , Interleucina-6/genética , MicroARNs/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/patologíaRESUMEN
Chronic obstructive pulmonary disease (COPD) is a complex disease, and its pathogenesis is influenced by genetic factors. This study aimed to evaluate the role of IL5RA genetic variation in the risk of COPD. In this study, 498 patients with COPD and 498 normal controls were recruited. Subsequently, five SNPs (rs3804795, rs2290610, rs13097407, rs334782, and rs3856850) in the IL5RA gene were genotyped. Logistic analysis examined the association of five single nucleotide polymorphisms (SNPs) in IL5RA with the risk of COPD under various genetic models. Furthermore, the association between IL5RA and susceptibility to COPD was comprehensively analyzed with stratification based on age, sex, smoking, and alcohol consumption. Our study showed that IL5RA rs13097407 reduced susceptibility to COPD (OR = 0.43, p < 0.001, p (FDR)< 0.001). On the other hand, rs3856850 was associated with an increased risk of COPD (OR = 1.71, p = 0.002, p (FDR) = 0.002). Interestingly, the effect of IL5RA SNPs on susceptibility to COPD was found to be influenced by factors such as sex and smoking. IL5RA gene variants were significantly associated with susceptibility to COPD.