Aim
The aim of this study was to investigate the underlying targets and mechanisms of action GXN in the treatment of diabetic atherosclerosis, employing a combination of network pharmacology, molecular docking, and in vitro experimental verification.
Conclusions
Our findings suggest that GXN can potentially safeguard endothelial cells from the adverse effects of high-glucose and high-fat by modulating the interactions between endoplasmic reticulum stress and autophagy. Therefore, GXN is a promising candidate for the prevention and treatment of diabetic atherosclerosis.
Methods
We predicted the core components and targets of GXN in the treatment of diabetic atherosclerosis through various databases, and made analysis and molecular docking. In vitro, we induced injury in human umbilical vein endothelial cells using glucose/palmitate and observed the effects of GXN on cellular damage high-glucose and high-fat conditions, subsequently elucidating its molecular mechanisms.
Results
A total of 14 active components and 157 targets of GXN were identified. Using the PPI network, we selected 9 core active components and 20 targets of GXN. GO functional analysis revealed that these targets were primarily associated with apoptosis signaling pathways in response to endoplasmic reticulum stress and reactive oxygen species responses. Molecular docking confirmed the strong binding affinities of the primary active components of GXN with ERN1, MAPK1 and BECN1. In vitro experiments demonstrated the ability of GXN to restore endothelial cell activity, enhance cell migration and inhibit sICAM secretion, and upregulate the expression of endoplasmic reticulum stress-related proteins (IRE1, XBP1) and autophagy-related proteins (Beclin1, LC3A, and LC3B), while simultaneously inhibiting endothelial cell apoptosis under high-glucose and high-fat conditions. Conclusions: Our findings suggest that GXN can potentially safeguard endothelial cells from the adverse effects of high-glucose and high-fat by modulating the interactions between endoplasmic reticulum stress and autophagy. Therefore, GXN is a promising candidate for the prevention and treatment of diabetic atherosclerosis.