Ganoderma lucidum spore ethanol extract attenuates atherosclerosis by regulating lipid metabolism via upregulation of liver X receptor alpha.

Context Ganoderma lucidum(Leyss.ex Fr.) Karst (Ganodermataceae) is a fungus that has been used in traditional Chinese medicine. Objective This is the first investigation of the lipid-lowering and anti-atherosclerotic effects ofGanoderma lucidumspore ethanol extract (EEG) in hyperlipidemic rabbits. Materials and methods Fifty-four Japanese rabbits were randomly divided into six groups (n = 9): control, model, atorvastatin and three EEG groups (6, 24 and 96 mg/kg/day, p.o.). Control group was administered a normal diet and other groups were administered a high-fat diet to induce hyperlipidaemia and atherosclerosis for 14 weeks. During this time, lipid profiles were recorded; lipid testing and histopathological examination of aorta and liver were conducted. LXR alpha and its downstream genes expression in the liver and small intestine were examined. The effect of EEG on macrophage cholesterol efflux and ABCA1/G1 expression was observed under silenced LXR alpha expression. Results EEG reduced serum cholesterol (20.33 +/- 3.62 mmol/L vs 34.56 +/- 8.27 mmol/L for the model group) and LDL-C, reduced the area of arterial plaques (24.8 +/- 10% vs 53.9 +/- 15.2% for the model group) and Intima/Medium thickness ratio, increased faecal bile acid content, upregulated LXR alpha, CYP7A1, ABCA1/G1, ABCG5/G8 expression in the liver, small intestine and macrophages. After silencing LXR alpha in macrophages, the ability of EEG to promote cholesterol efflux was inhibited. Discussion and conclusion EEG exert lipid-lowering and anti-atherosclerotic effects via upregulating expression of LXR alpha and downstream genes associated with reverse cholesterol transport and metabolism. However, whether PPAR alpha/gamma are involved in the up-regulation of LXR expression by EEG remains to be elucidated.