Chimonanthus salicifolius attenuated vascular remodeling by alleviating endoplasmic reticulum stress in spontaneously hypertensive rats

Abstract

Chimonanthus salicifolius (CS), the leaves of Chimonanthus salicifolius S. Y. Hu., is an effective tea to prevent and treat hypertension in China. This study aimed to explore the effect and mechanism of CS in the protection against vascular remodeling in hypertension. Spontaneously hypertensive rats (SHRs) were orally administered with aqueous extracts of CS for 6 months. The blood pressure and morphological changes of the aorta were measured. Their mechanisms were studied by combining chemical identification, network pharmacology analysis and validation in vivo. Hypertensive rats showed an impaired vascular structure and dyslipidemia as illustrated by the increase of the vascular media thickness and collagen deposition in the aorta. CS treatment exhibited significant beneficial effects on blood pressure control and aortal morphology. A total of 21 compounds from CS were identified, which were linked to 106 corresponding targeted genes for vascular remodeling. The network pharmacology predicted that CS prevented vascular remodeling through the endoplasmic reticulum stress pathway. The in vivo experiments further showed that CS treatment upregulated Glucose-Regulated Protein 78 and downregulated CCAAT-enhancer-binding protein homologous protein at both mRNA and protein levels, paralleling reduced apoptotic cells in the arterial wall. Additionally, CS diminished the low-density lipoprotein cholesterol levels, total cholesterol contents and triglyceride/high-density lipoprotein cholesterol ratios in the sera of SHRs, which might also contribute to its protection of vessels. Collectively, CS protects against vascular modeling by suppressing endoplasmic reticulum stress-related apoptosis in hypertension, and it could be a potential agent for the prevention and treatment of vascular modeling.