黄精在糖尿病并发症中"异病同治"机制的网络药理学研究OA

Objective To investigate the molecular mechanisms of Huangjing(Polygonati Rhizoma)in exerting the"treating different diseases with the same approach"effect on diabetic complications based on network pharmacology and molecular docking methods.Methods The active ingredients and related targets of Huangjing(Polygonati Rhizoma)were obtained from the TCMSP database and standardized using the UniProt database.Targets related to diabetic cardiomyopathy,diabetic nephropathy,metabolic dysfunction-associated fatty liver disease,diabetic peripheral neuropathy,and diabetic retinopathy were collected from the OMIM and GeneCards databases,and their intersection was identified to obtain common targets of diabetic complications.Subsequently,the intersection between the active ingredient targets of Huangjing(Polygonati Rhizoma)and diabetic complication targets was derived to obtain the targets of Huangjing(Polygonati Rhizoma)for treating diabetic complications.These targets were then imported into the STRING database for protein-protein interaction(PPI)analysis to screen for key targets.Meanwhile,the targets were also imported into the Metascape database for GO and KEGG enrichment analyses to identify key pathways.Finally,molecular docking was performed using the CB-Dock2 platform to validate the binding affinity between the active ingredients of Huangjing(Polygonati Rhizoma)and the key targets.Results A total of seven active ingredients of Huangjing(Polygonati Rhizoma)for treating diabetic complications were identified,including diosgenin,sitosterol,baicalein,liquiritigenin,(2R)-7-hydroxy-2-(4-hydroxyphenyl)chroman-4-one,(+)-syringaresinol-O-β-D-glucoside,and β-sitosterol.The databases provided 84 targets of active ingredients in Huangjing(Polygonati Rhizoma)and 403 common targets of diabetic complications,with 23 overlapping targets considered potential therapeutic targets.PPI network identified six key targets:MMP9,TP53,CASP3,AKT1,PPARG,and PTGS2.GO enrichment analysis indicated that biological processes were mainly involved in the regulation of apoptosis,oxidative stress response,and small molecule metabolism;molecular functions were mainly associated with ubiquitin ligase binding and antioxidant activity;and cellular components were mainly related to mitochondrial structures and neuronal cytoplasm.KEGG pathway analysis revealed that the targets were primarily enriched in endocrine resistance,apoptosis,and IL-17 signaling pathways.Molecular docking results demonstrated that the seven active ingredients had good binding affinity with the aforementioned targets.Conclusion This study screened out seven active ingredients of Huangjing(Polygonati Rhizoma)for the treatment of diabetic complications,and predicted MMP9,TP53,CASP3,AKT1,PPARG,and PTGS2 as the key targets of Huangjing(Polygonati Rhizoma)in the mechanism of"treating different diseases with the same approach"in diabetic complications.The underlying mechanisms may involve multiple pathways,including endocrine resistance,apoptosis,and IL-17 signaling pathways.