Exploration of the Potential and Mechanisms of Diabetic Cognitive Disorder Modulation by Daehwangmokdanpi-tang through a Network Pharmacological Approach

Yebin Lim, Bitna Kweon, Dong-Uk Kim, Do-Eun Lee, Jungtae Leem, Dong-Gu Kim, Hyung Won Kang, Gi-Sang Bae
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Abstract

Objectives: This study utilized a network pharmacology approach to investigate the potential therapeutic effects and underlying mechanisms of Daehwangmokdanpi-tang (DHMDPT) in diabetic cognitive disorder (DCD).Methods: The compounds of DHMDPT and their target genes were obtained from the OASIS and PubChem databases. These putative target genes were compared with known targets of DCD to identify potential correlations. Using Cytoscape 3.10.2, a network was constructed to highlight key target genes. To further elucidate the underlying mechanisms, functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, CB-DOCK was used to assess binding affinities and confirm the interactions.Results: The results showed that a total of 27 compounds and 439 related genes were identified from DHMDPT. Among these, 373 genes interacted with the DCD gene set, indicating a close relationship between the effects of DHMDPT and DCD. Through GO enrichment analysis and KEGG pathways, ‘Regulation of Apoptotic Process’, ‘Cytokine-Mediated signaling pathway’, and ‘AGE-RAGE signaling pathway in diabetic complications’ were identified as the functional pathways of the 18 key target genes of DHMDPT on DCD. Additionally, molecular docking was performed to assess the binding affinities of the six most highly associated key target genes of DCD with active compounds.Conclusions: Using a network pharmacology approach, which included molecular docking, DHMDPT was found to be highly relevant to DCD. This study could serve as a foundation for further research on the cognitive enhancement effects of DHMDPT in DCD.
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通过网络药理学方法探索大王木丹皮汤调节糖尿病认知障碍的潜力和机制
研究目的本研究采用网络药理学方法研究大王木丹皮汤(DHMDPT)对糖尿病认知障碍(DCD)的潜在治疗作用及其内在机制:方法:从 OASIS 和 PubChem 数据库中获取 DHMDPT 的化合物及其靶基因。方法:从 OASIS 和 PubChem 数据库中获取了 DHMDPT 的化合物及其靶基因,并将这些推测的靶基因与 DCD 的已知靶基因进行比较,以确定潜在的相关性。使用 Cytoscape 3.10.2 构建了一个网络,以突出关键靶基因。为了进一步阐明潜在的机制,利用基因本体(GO)和京都基因组百科全书(KEGG)通路进行了功能富集分析。最后,使用 CB-DOCK 评估结合亲和力并确认相互作用:结果表明,DHMDPT 共鉴定出 27 种化合物和 439 个相关基因。结果表明,DHMDPT共鉴定出27种化合物和439个相关基因,其中373个基因与DCD基因集发生相互作用,表明DHMDPT的作用与DCD有密切关系。通过GO富集分析和KEGG通路分析,"凋亡过程调控"、"细胞因子介导的信号通路 "和 "糖尿病并发症中的AGE-RAGE信号通路 "被确定为DHMDPT对DCD影响的18个关键靶基因的功能通路。此外,还进行了分子对接,以评估与DCD关联度最高的6个关键靶基因与活性化合物的结合亲和力:结论:利用包括分子对接在内的网络药理学方法,发现 DHMDPT 与 DCD 高度相关。这项研究可为进一步研究 DHMDPT 对 DCD 的认知增强作用奠定基础。
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