Ganoderma lucidum triterpenoids and polysaccharides attenuate atherosclerotic plaque in high-fat diet rabbits.

BACKGROUND AND AIMS: Atherosclerosis is characterized by lipid deposition, oxidative stress, and inflammation in the arterial intima. Ganoderma lucidum triterpenoids (GLTs) and polysaccharides (GLPs) are traditional Chinese medicines with potential cardiovascular benefits. We aimed to comprehensively evaluate the effect of GLTs and GLPs on atherosclerosis and the associated underlying mechanisms in vivo and in vitro. METHODS AND RESULTS: Japanese big-ear white rabbits were randomly divided into three groups of blank, model, and treatment, and the treatment group was fed with GLSO and GLSP (0.3 g/kg body-weight/day) for 4 months. Serum levels of triglyceride (TG), total (TC), and low density lipoprotein cholesterol (LDL-C) in GL treatment group were significantly lower than those in the model group. The area of aortic plaques was significantly reduced in the treatment group. Further, GL administration in oxidized low-density lipoprotein (ox-LDL) stimulated human umbilical vein endothelial cells (HUVECs) reduced the generation of reactive oxygen species (ROS) and malondialdehyde (MDA) by inhibiting the upregulation of the nuclear transcription factor (NF)-κB p65 and the relative receptor LOX-1. In THP-1 cells treated with phorbol myristate acetate, GL inhibited the inflammatory polarization of macrophages (as evidenced by reduced TNF-α levels) via regulation of Notch1 and DLL4 pathways. Ox-LDL-stimulated THP-1 cells treated with GL showed an increase in the apoptosis of foam cells. CONCLUSIONS: GLTs and GLPs attenuated the progression of atherosclerosis by alleviating endothelial dysfunction and inflammatory polarization of macrophages, thus promoting apoptosis of foam cells.