Scholarlink

<p>Type 2 diabetes (T2D) manifests on account of insulin resistance and dysfunction of pancreatic islet cells. A key strategy in the treatment of T2D is protecting β-cells from undergoing apoptosis as well as dedifferentiation. This study aims at elucidating the pathophysiology of pancreatic islet cells and exploring potential of three selected phenolics in its treatment. Transcriptomics analysis was carried out using three data sets from pancreatic islets. Proteomics analysis was performed using one dataset obtained from pancreatic islets and five datasets from plasma of T2D patients. Based on the gene expression data, associated transcription factors (TFs), kinases and relevant pathways were analyzed. Mitogen-Activated Protein Kinase (MAPK) signaling pathway was upregulated across all nine datasets studied implying its importance in the pathogenesis of T2D. On the other hand, two TFs KLF4 and TCFL1 associated with Wnt/β-catenin-signaling pathway were dysregulated across the transcriptomics datasets studied. Protein-protein interaction (PPI) networking and hub gene analysis of the principal data set from pancreatic islets showed seven out of ten upregulated hub genes were associated with advanced glycation end product (AGE)-receptor of AGE (AGE-RAGE) pathways, while six out of ten downregulated hub genes were related to oxidative phosphorylation (OXPHOS) suggesting that oxidative stress and mitochondrial dysfunction are the key reasons for islet cell failure. Network pharmacology of EUPANO (Eugenol, Protocatechuic Acid, and Nobiletin) showed these compounds act synergistically on key pancreatic islet targets linked to T2D. Using hub genes that were identified based on transcriptomic data and multi-platform in silico validation (3DSTarPred, AmIActive, and ChEMBL), we substantiated interactions between EUPANO and proteins such as GSK3B, MTOR, IL1B and JUN. This multi-target approach highlights the potential of EUPANO to modulate insulin signaling and inflammatory pathways, thereby offering protection against pancreatic islet dysfunction and T2D progression.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Network pharmacology approach to the study of therapeutic role of selected phenolics on diabetic pancreatic islet cells based on multi-omics analysis

  • 期刊论文

  • 发表日期：

    2025年10月15日

查看全文
  • Sai Anand,
  • Kannakazhi Kantari,
  • Piyush Kumar,
  • Sai Sanwid Pradhan,
  • Ashok Agraharam

摘要

Type 2 diabetes (T2D) manifests on account of insulin resistance and dysfunction of pancreatic islet cells. A key strategy in the treatment of T2D is protecting β-cells from undergoing apoptosis as well as dedifferentiation. This study aims at elucidating the pathophysiology of pancreatic islet cells and exploring potential of three selected phenolics in its treatment. Transcriptomics analysis was carried out using three data sets from pancreatic islets. Proteomics analysis was performed using one dataset obtained from pancreatic islets and five datasets from plasma of T2D patients. Based on the gene expression data, associated transcription factors (TFs), kinases and relevant pathways were analyzed. Mitogen-Activated Protein Kinase (MAPK) signaling pathway was upregulated across all nine datasets studied implying its importance in the pathogenesis of T2D. On the other hand, two TFs KLF4 and TCFL1 associated with Wnt/β-catenin-signaling pathway were dysregulated across the transcriptomics datasets studied. Protein-protein interaction (PPI) networking and hub gene analysis of the principal data set from pancreatic islets showed seven out of ten upregulated hub genes were associated with advanced glycation end product (AGE)-receptor of AGE (AGE-RAGE) pathways, while six out of ten downregulated hub genes were related to oxidative phosphorylation (OXPHOS) suggesting that oxidative stress and mitochondrial dysfunction are the key reasons for islet cell failure. Network pharmacology of EUPANO (Eugenol, Protocatechuic Acid, and Nobiletin) showed these compounds act synergistically on key pancreatic islet targets linked to T2D. Using hub genes that were identified based on transcriptomic data and multi-platform in silico validation (3DSTarPred, AmIActive, and ChEMBL), we substantiated interactions between EUPANO and proteins such as GSK3B, MTOR, IL1B and JUN. This multi-target approach highlights the potential of EUPANO to modulate insulin signaling and inflammatory pathways, thereby offering protection against pancreatic islet dysfunction and T2D progression.