Ginsenosides regulation of lysophosphatidylcholine profiles underlies the mechanism of Shengmai Yin in attenuating atherosclerosis
Yun Wang, Jiawei Wu, Jia‐Ying Zhu, Chujie Ding, Wanfeng Xu, Haiping Hao, Jun Zhang, Guangji Wang, Lijuan Cao
Abstract
The traditional Chinese medicine (TCM) preparation, Shengmai Yin (SMY), is widely applied in cardiovascular disease treatments. However, the pharmacological mechanism of its therapeutic effects has not been fully clarified. This study aimed to clearly define the efficacy and underlying mechanism of SMY and its active components in protecting against atherosclerosis. The pharmacological effects of SMY and its components were evaluated upon a mouse hypercholesteremia model induced by a high cholesterol diet (HCD) for 12 weeks and Apoe−/− mice, a mouse atherosclerosis model. Pathological indicators including serum cholesterol levels, cytokines and histological changes in aortic root plaques were assessed. Untargeted metabolomic, untargeted lipidomic and targeted lipidomic changing profiles were investigated to clarify pharmacological mechanisms. SMY and red ginseng crude extracts (GE) significantly decreased the serum cholesterol levels in hypercholesteremia mice and reduced the aortic root plaque areas and exerted antiatherogenic efficacy in Apoe−/− mice. Moreover, total red ginseng saponin extracts (TGS) showed the most apparent improvement on maintaining lipid homeostasis, representing the effects of red ginseng in SMY on atherosclerosis treatment. Mechanically, TGS inhibited serum secreted phospholipase A2 (sPLA2) activity and lowered the serum levels of lysophosphatidylcholine (lysoPC), which is a risk factor for atherosclerosis. Our findings revealed that ginsenosides from SMY exerted therapeutic effects on atherosclerosis by maintaining lipid homeostasis including cholesterol and lysoPCs.