Gypenoside XLIX Ameliorate High-Fat Diet-Induced Atherosclerosis via Regulating Intestinal Microbiota, Alleviating Inflammatory Response and Restraining Oxidative Stress in ApoE−/− Mice

Abstract

A high-fat choline diet (HFCD)-induced atherosclerosis model in ApoE−/− mice was established to explore the anti-atherosclerotic effects of gypenoside XLIX (GPE). It was found that HFCD-induced atherosclerotic index such as dyslipidemia, atherosclerotic plaque, inflammation, and gut microbiota dysfunction could be reduced by GPE treatment. GPE treatment could decrease Verrucomicrobia, Proteobacteria, and Actinobacteria abundance, and increase Firmicutes and Bacteroidetes population. Moreover, the Firmicutes/Bacteroidetes ratio increased significantly after treatment with GPE. After treatment with GPE, the relative abundance of trimethylamine-producing intestinal bacteria Clostridioides and Desulfovibrionaceae decreased while butyrate-producing bacteria such as Eubacterium, Roseburia, Bifidobacterium, Lactobacillus, and Prevotella increased significantly. The GPE group demonstrated higher SCFAs concentrations in the fecal sample, such as Acetic Acid, Propionic Acid, and Butyric Acid. Further pathway analysis showed that 29 metabolic pathways were appreciably disturbed during GPE treatment, including citrate cycle (TCA cycle); galactose and glycero-lipid-metabolism biosynthesis of unsaturated fatty acids, fatty acid biosynthesis. This study suggests that the anti-atherosclerotic effect of GPE is related to the substantial changes in intestinal microbiota and anti-inflammatory activity.

Effects of Berries, Phytochemicals, and Probiotics on Atherosclerosis through Gut Microbiota Modification: A Meta-Analysis of Animal Studies

“…Considering sex, 9 studies used males, 10 used females, only 2 included males and females and 5 did not report the sex of the mice. Considering the type of intervention, 17 studies tested berries, polyphenols or berberine [ 22 , 23 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ] and 9 used probiotics [ 11 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ]. The intervention duration varied from 4 to 16 weeks of treatment, and all the studies used HFD to induce plaque.…”

“…With respect to the microbiome, only 10 studies reported F/B ratios. For atherosclerosis quantification, all of the included studies, except for one [ 37 ], reported aortic plaque size, which was reported for the aortic root (7 studies) [ 32 , 33 , 36 , 40 , 47 , 48 , 49 ], the arch (4 studies) [ 34 , 35 , 42 , 46 ], the aortic sinus (11 studies) [ 11 , 28 , 29 , 30 , 31 , 38 , 40 , 41 , 43 , 44 , 45 ] and in the whole aorta (7 studies) [ 22 , 23 , 27 , 28 , 35 , 39 , 46 ]. The study by Yang et al [ 37 ] reported a reduction in plaque in the aortic sinus by the intervention, but no quantification was provided.…”

Advances in the Bioactivities of Phytochemical Saponins in the Prevention and Treatment of Atherosclerosis

“…Gynostemma pentaphyllum (Thunb.) Makino is an ancient Chinese herbal medicine and tea [ 87 ], and is known for its effects in reducing blood pressure, hypolipidemia, hypoglycemia and anti-aging [ 17 ]. Gypenoside has been identified as the most important functional component of Gynostemma pentaphyllum .…”

“…There are more than 160 types of gypenoside that have been classified into 12 classes, such as gypenoside III, IV, VII, XII, I, Gyp-A-AH and XLIX, etc. [ 17 , 87 ]. Gypenosides possess a number of bioactivities including anti-atherogenesis, anti-inflammation, anti-cancer, neuroprotection, hepatoprotection and adjusting lipidemia [ 88 , 89 ].…”

“…Furthermore, gypenoside XLIX could inhibit the TNF-α-induced expression and activity of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs [ 103 ]. More recently, gypenoside XLIX was found to ameliorate HFD-induced AS through regulating intestinal microbiota, alleviating inflammatory response and restraining oxidative stress in ApoE −/− mice [ 87 ]. Gypenoside XVII prevented AS by attenuating endothelial apoptosis and oxidative stress via the regulation of the ERalpha-mediated PI3K/Akt pathway in ApoE −/− mice [ 104 ].…”