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：

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基于通路的蛋白质-蛋白质关联网络探索黄芩α-葡萄糖苷酶抑制剂抗2型糖尿病的机制。

天然产物已广泛用于治疗2型糖尿病（T2D）。然而，由于多成分和多目标，它们的机制常常被掩盖。作者针对从黄芩 (SBG) 中鉴定出的 13 种 α-葡萄糖苷酶抑制剂 (AGI) 的靶蛋白构建了一个基于通路的蛋白质-蛋白质关联 (PPA) 网络，旨在探索其潜在机制。该网络包含 118 个节点和 1167 个连接。观察到度分布不均匀和小世界特性，其特点是聚类系数高和平均路径长度短。PPA 网络具有固有的层次结构 C(k)∼k-0.71 。它还表现出潜在的弱不配体混合模式，伴随着函数 Knn (k) 的降低和配体系数的负值。这些属性表明一些节点对于网络至关重要。PGH2、GNAS、MAPK1、MAPK3、PRKCA 和 MAOA 被确定为具有最高程度值和中心性指数的关键目标。此外，核心子网络显示白杨素、5,8,2'-三羟基-7-甲氧基黄酮和汉黄芩素是这些 AGI 的主要活性成分，并且血清素突触途径是 SBG 对抗 T2D 的关键途径。基于通路的蛋白质-蛋白质关联网络的应用为探索天然产物对复杂疾病的作用机制提供了新的策略。