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Pathway-based protein-protein association network to explore mechanism of α-glucosidase inhibitors from Scutellaria baicalensis Georgi against type 2 diabetes.
IET Systems Biology ( IF 2.3 ) Pub Date : 2021-04-26 , DOI: 10.1049/syb2.12019
Le Wang 1 , Wenbo Diwu 1 , Nana Tan 1 , Huan Wang 2 , Jingbo Hu 3 , Bailu Xu 1 , Xiaoling Wang 1
Affiliation  

Natural products have been widely used in the treatment of type 2 diabetes (T2D). However, their mechanisms are often obscured due to multi-components and multi-targets. The authors constructed a pathway-based protein-protein association (PPA) network for target proteins of 13 α-glucosidase inhibitors (AGIs) identified from Scutellaria baicalensis Georgi (SBG), designed to explore the underlying mechanisms. This network contained 118 nodes and 1167 connections. An uneven degree distribution and small-world property were observed, characterised by high clustering coefficient and short average path length. The PPA network had an inherent hierarchy as C(k)∼k-0.71 . It also exhibited potential weak disassortative mixing pattern, coupled with a decreased function Knn (k) and negative value of assortativity coefficient. These properties indicated that a few nodes were crucial to the network. PGH2, GNAS, MAPK1, MAPK3, PRKCA, and MAOA were then identified as key targets with the highest degree values and centrality indices. Additionally, a core subnetwork showed that chrysin, 5,8,2'-trihydroxy-7-methoxyflavone, and wogonin were the main active constituents of these AGIs, and that the serotonergic synapse pathway was the critical pathway for SBG against T2D. The application of a pathway-based protein-protein association network provides a novel strategy to explore the mechanisms of natural products on complex diseases.

中文翻译:

基于通路的蛋白质-蛋白质关联网络,探索黄cut中α-葡萄糖苷酶抑制剂对2型糖尿病的作用机制。

天然产物已被广泛用于治疗2型糖尿病(T2D)。但是,由于多组件和多目标,它们的机制经常被遮盖。作者构建了一种基于路径的蛋白质-蛋白质协会(PPA)网络,用于从黄cut(SBG)中鉴定出的13种α-葡萄糖苷酶抑制剂(AGI)的目标蛋白质,旨在探索其潜在机制。该网络包含118个节点和1167个连接。观测到不均匀度分布和小世界属性,其特征是聚类系数高且平均路径长度短。PPA网络的固有层次为C(k)〜k-0.71。它也表现出潜在的弱分散性混合模式,并伴随着函数Knn(k)的减小和分配系数的负值。这些属性表明,一些节点对于网络至关重要。然后,将PGH2,GNAS,MAPK1,MAPK3,PRKCA和MAOA确定为具有最高度值和中心指数的关键目标。此外,一个核心子网显示,菊花蛋白,5,8,2'-三羟基-7-甲氧基黄酮和沃戈宁是这些AGI的主要活性成分,而血清素能突触途径是SBG抵抗T2D的关键途径。基于途径的蛋白质-蛋白质关联网络的应用为探索天然产物对复杂疾病的机制提供了一种新颖的策略。-三羟基-7-甲氧基黄酮和wogonin是这些AGI的主要活性成分,而血清素能突触途径是SBG抗T2D的关键途径。基于途径的蛋白质-蛋白质关联网络的应用为探索天然产物对复杂疾病的机制提供了一种新颖的策略。-三羟基-7-甲氧基黄酮和wogonin是这些AGI的主要活性成分,而血清素能突触途径是SBG抗T2D的关键途径。基于途径的蛋白质-蛋白质关联网络的应用为探索天然产物对复杂疾病的机制提供了一种新颖的策略。
更新日期:2021-04-26
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