Sennoside A Ameliorates Diabetic Atherosclerosis by Inhibiting OSCP1/ERK1/2 Pathway to Regulate Endothelial...

Area of Science:

• Biochemistry
• Pharmacology
• Cardiovascular Research

Background:

• Atherosclerosis (AS) is a major complication in type 2 diabetes mellitus (T2DM).
• Identifying effective treatments for AS in T2DM patients is crucial.

Purpose of the Study:

• To investigate the therapeutic effects of sennoside A (SA) on AS in T2DM mice.
• To elucidate the underlying molecular mechanisms of SA's action.

Main Methods:

• Animal model: T2DM mice induced by high-fat diet and streptozotocin, treated with SA or metformin.
• In vitro model: Endothelial cells exposed to high glucose and oxidized low-density lipoprotein (ox-LDL).
• Analyses included biochemical assays, histological staining, RT-qPCR, and Western blot to assess AS progression, endothelial dysfunction, and molecular pathway activation.

Main Results:

• SA treatment improved glycemic control, lipid profiles, and insulin sensitivity in T2DM mice, reducing AS plaque area.
• SA inhibited high glucose/ox-LDL-induced endothelial cell dysfunction, proliferation, migration, and invasion.
• SA downregulated the OSCP1/ERK1/2 signaling pathway, decreasing protein levels of OSCP1, MMP9, VEGFA, and p-ERK1/2.

Conclusions:

• SA demonstrates significant anti-atherosclerotic effects in T2DM mice.
• SA's mechanism involves downregulating the OSCP1/ERK1/2 pathway, thereby reversing endothelial-to-mesenchymal transition and stabilizing plaques.