Morin ameliorates chronic obstructive pulmonary disease by inhibiting the expression of MMP9

Acta Universitatis Medicinalis Anhui     font:big middle small

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Authors:Leng Anming, Yang Jing, Zhang Kui

Keywords:chronic obstructive pulmonary disease;morin;network pharmacology;MMP9;inflammatory reaction

DOI:10.19405/j.cnki.issn1000-1492.2023.12.001

〔Abstract〕 Objective To investigate the effects of morin on chronic obstructive pulmonary disease(COPD) animal and cell model through the regulation of matrix metalloproteinase-9(MMP9). Methods SwissTargetPrediction database was used to predict the genetargets of morin, GeneCards, OMIMand DisGenet databases were used to predict the risk genes of COPD, the intersection of COPD-related gene targets and morin gene targets was obtained by using Venny online website; Protein-protein interaction(PPI) analysis was performed using the String database, and topological analysis was performed by Cytoscape 3.8.2 software. Molecular docking was used to validate the interaction between the drug components and gene targets; COPD rat models were constructed to verify the therapeutic effects of morin om COPD rat models. The COPD cell model was established to interfere with the expression of MMP9 in the cells. COPD cell models were established and the expression ofMMP9in cells was intervened; flow cytometry was used to detect cell apoptosis rate; ELISA was used to measure the concentration of inflammatory factors. Results The Swiss Target Prediction database predicted 96 gene targets of morin. GeneCards, OMIM, and DisGenet databases predicted 7 122 gene targets of COPD, intersection analysis identified 67 common gene targets between morin and COPD. Topological analysis revealed that the top 5 gene targets with strongest interactions among the intersected targets wereSRC,MMP9,MMP2,PTGS2, andFURIN; Molecular docking results showed the best binding activity betweenMMP9and morin; animal experiments showed that morin improved respiratory function parameters and lung tissue pathological damage, and inhibited MMP9 expression in COPD rats(P<0.05); Cell experiments showed that morin increased cell viability in COPD cell models and inhibited MMP9 expression(P<0.05). In addition, morin inhibited cell apoptosis and expression of inflammatory factors in the COPD cell model, but this effect was reversed by overexpression of MMP9(P<0.05). Conclusion Morin can improve apoptosis and and expression of inflammatory cytokines in COPD cell model, reduce lung tissue pathological changes by inhibiting MMP9 expression.