Phenylethanoid glycosides extract from Cistanche deserticola ameliorates atherosclerosis in apolipoprotein E-deficient mice and regulates intestinal PPAR gamma-LXR alpha-ABCA1 pathway

Objectives This study was aimed to evaluate the protective effects of phenylethanoid glycosides extract from Cistanche deserticola against atherosclerosis and its molecular mechanism. Methods Total phenylethanoid glycosides were extracted and purified from C. deserticola, and the C. deserticola extract (CDE) was used to treat a mice model of atherosclerosis. Key findings CDE containing 81.00% total phenylethanoid glycosides, with the contents of echinacoside and acteoside being 31.36% and 7.23%, respectively. A 13-week of CDE supplementation (1000 mg/kg body weight/day) significantly reduced atherosclerotic lesions in the aortic sinus and entire aorta in ApoE(-/-) mice fed with a high-fat diet. In addition, varying doses of CDE (250, 500 and 1000 mg/kg body weight/day) lowered plasma total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels. Transcriptomic analysis of the small intestine revealed the changes enriched in cholesterol metabolic pathway and the activation of Abca1 gene. Further validation using real-time quantitative PCR and western blot confirmed that CDE significantly increased the mRNA levels and protein expressions of ABCA1, LXR alpha and PPAR gamma. Conclusions Our results demonstrate the beneficial effects of C. deserticola on atherosclerotic plaques and lipid homeostasis, and it is, at least partially, by activating PPAR gamma-LXR alpha-ABCA1 pathway in small intestine.