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.
© 2021 The Authors. IET Systems Biology published by John Wiley & Sons Ltd on behalf of The Institution of Engineering and Technology.