The potential molecular mechanism underlying gypenoside amelioration of atherosclerosis in ApoE−/− mice: A multi-omics investigation
Xing Ju,
Yufeng Liu,
Ying Wang,
Guoyuan Sui,
Yixin Ma,
Huimin Cao,
Yuan Cao,
Jin Wu,
Ying Du,
Xue Leng,
Lianqun Jia,
Guanlin Yang
Affiliations
Xing Ju
TCM Innovation Engineering Technology Center, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China; Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China
Yufeng Liu
Center for Medical Research on Innovation and Translation, Guangzhou First People' S Hospital, Guangzhou, 510180, China
Ying Wang
TCM Innovation Engineering Technology Center, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China; Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China
Guoyuan Sui
School of Integrated Traditional Chinese and Western Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China
Yixin Ma
TCM Innovation Engineering Technology Center, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China; Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China
Huimin Cao
TCM Innovation Engineering Technology Center, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China; Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China
Yuan Cao
TCM Innovation Engineering Technology Center, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China; Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China
Jin Wu
TCM Innovation Engineering Technology Center, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China; Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China
Ying Du
TCM Innovation Engineering Technology Center, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China; Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China
Xue Leng
School of Integrated Traditional Chinese and Western Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China
Lianqun Jia
Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China; Corresponding author.
Guanlin Yang
Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China; Corresponding author.
Gypenosides (Gyp) are bioactive components of Gynostemma pentaphyllum that have a variety of pharmacological properties. Extracts of G. pentaphyllum have been found to be effective in the reduction of blood sugar and lipids and prevention of atherosclerosis. Here, the functions of Gyp and the mechanisms underlying their effects on atherosclerosis were investigated. Mice were allocated to three groups, namely, the control (C57BL/6), atherosclerosis model (ApoE−/− mice with high-fat diet), and Gyp-treated groups. Differentially expressed mRNAs, miRNAs, circRNA, and differential metabolites among the groups were analyzed. The results showed that “Fatty acid metabolism”, “Fatty acid elongation”, “Cytokine-cytokine receptor interaction”, and “PI3K-Akt signaling pathway”, amongst others, were involved in treatment process. Differentially expressed genes, including Fabp1, Apoe, FADS1, ADH1, SYNPO2, and Lmod1were also identified. Mmu-miR-30a and mmu-miR-30e showed reduced expression in atherosclerosis models but were increased following Gyp treatment, suggesting involvement in the effects of Gyp. In addition, chr5:150604177-150608440 were found to interact with mmu-miR-30a and mmu-miR-30e to regulate their abundance. In terms of metabolomics, Gyp may regulate biological processes involving PGD2 and PGJ2, potentially alleviating atherosclerosis. In conclusion, Gyp appeared to have complex effects on atherosclerosis, most of which were positive. These results support the use of Gyp in the treatment of atherosclerosis.
