Platycodin D Improves Early Atherosclerosis in Type 2 Diabetes Mellitus by Regulating Endothelial Inflammation and Apoptosis.

Abstract

Atherosclerosis (AS) is a risk factor for cardiovascular complications, induced by Type 2 diabetes mellitus (T2DM), which greatly increases the mortality of patients. Previous studies explored the potential molecular mechanism of Platycodin D (PD) in its capacity as a treatment of AS through network pharmacology, and obtained the potential targets of PD treatment of AS. Therefore, this paper conducted a more in-depth study on the anti-Type 2 diabetes mellitus-Atherosclerosis (T2DM-AS) activity of PD. By establishing a T2DM-AS mice model induced by high-fat diet (HFD) combined with streptozotocin (STZ), and human umbilical vein endothelial cell (HUVEC) injury models induced by lipopolysaccharide (LPS), both the NLRP3 inflammatory body and endoplasmic reticulum stress (ERS) were studied. This study focused on ERS activation to explore the regulatory effect and mechanism of PD on the inflammation and apoptosis of aorta and endothelial cells. It was found that PD (2.5[Formula: see text]mg/kg) could improve early AS inflammation and lipid translocation deposition in T2DM mice. PD could also alleviate the LPS-induced apoptosis of HUVECs at concentrations of 0.5, 1, and 2[Formula: see text][Formula: see text]M by regulating the PI3K/AKT pathway, and ameliorate inflammation by inhibiting the activation of the NLRP3 inflammasome and the NF-[Formula: see text]B pathway. Both in vivo and in vitro experiments showed that PD could regulate the activation of NLRP3 inflammasome, inhibit endothelial cell inflammation and cell apoptosis caused by ERS, and improve AS inflammation and lipid deposition in the early stage of T2DM by restoring damaged cell function. This study provided a theoretical reference for its clinical treatment and the development and application of health care products.