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Metabolomics of the Protective Effect of Ampelopsis grossedentata and Its Major Active Compound Dihydromyricetin on the Liver of High-Fat Diet Hamster.

ABSTRACT: The flavonoid dihydromyricetin (DMY) is the main component of Ampelopsis grossedentata (Hand-Mazz) W. T. Wang (AG), a daily beverage and folk medicine used in Southern China to treat jaundice hepatitis, cold fever, and sore throat. Recently, DMY and AG were shown to have a beneficial effect on lipid metabolism disorder. However, the mechanisms of how DMY and AG protect the liver during lipid metabolism disorder remain unclear. In this study, we first analyzed the chemical compounds of AG by HPLC-DAD-ESI-IT-TOF-MS n . Of the 31 compounds detected, 29 were identified based on previous results. Then, the effects of DMY and AG on high-fat diet hamster livers were studied and the metabolite levels and metabolic pathway activity of the liver were explored by 1H NMR metabolomics. Compared to the high-fat diet group, supplementation of AG and DMY attenuated the high-fat-induced increase in body weight, liver lipid deposition, serum triglycerides and total cholesterol levels, and normalized endogenous metabolite concentrations. PCA and PLS-DA score plots demonstrated that while the metabolic profiles of hamsters fed a high-fat diet supplemented with DMY or AG were both far from those of hamsters fed a normal diet or a high-fat diet alone, they were similar to each other. Our data suggest that the underlying mechanism of the protective effect of DMY and AG might be related to an attenuation of the deleterious effect of high-fat diet-induced hyperlipidemia on multiple metabolic pathways including amino acid metabolism, ketone body metabolism, energy metabolism, tricarboxylic acid cycle, and enhanced fatty acid oxidation.

SUBMITTER: Fan L

PROVIDER: S-EPMC7007936 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Oxidative stress is recognized as a significant contributor to the development and progression of inflammation and disruptions in the balance of gut microflora, commonly referred to as intestinal dysbiosis. It is crucial that safe and effective antioxidant and anti-inflammatory agents are identified to address these conditions. Ampelopsis grossedentata, a natural plant abundant in flavonoids and primarily found in southern China, has demonstrated potent antioxidant properties. However, the extent to which flavonoids in A. grossedentata impact intestinal inflammation and alter the composition of the gut microbiome remains to be fully understood. The purpose of this study was to explore the potential benefits of using A. grossedentata as an antioxidant and anti-inflammatory agent in the context of intestinal inflammation, both in vitro and in vivo. We first conducted an initial comparison of the effects of dihydromyricetin (DMY), an alcohol extract of A. grossedentata (AEA, 82% total flavonoids), and a water extract of A. grossedentata (WEA, 57% total flavonoids) on the cell viability and intestinal barrier integrity of porcine epithelial cells IPEC-J2. Although the total flavonoid content is much lower in WEA than in AEA, the results show that they have similar effects. Subsequently, the antioxidant properties of WEA were compared with those of commonly utilized antioxidants in vitro. Lastly, the antioxidant and anti-inflammatory properties of WEA, as well as its impacts on gut microbiota, were evaluated in animal models, including mice and Drosophila. In summary, the results of our study indicate that WEA, due to its antioxidant properties, exhibits a protective effect on the intestinal barrier function in porcine epithelial cell line IPEC-J2. Additionally, WEA demonstrates a positive correlation with DPPH, ABTS radical scavenging rate, FRAP, and reducing power under in vitro settings. Furthermore, WEA was shown to effectively alleviate oxidative stress in animal models by reducing the levels of pro-inflammatory cytokines and increasing the antioxidant enzyme activity in the liver, as well as by activating the Nrf2 signaling pathway in the duodenum. Additionally, WEA was able to regulate gut microbiota, promoting the growth of beneficial bacteria and inhibiting harmful microbes, as well as extending the lifespan of Drosophila. Overall, these findings suggest that WEA may serve as a valuable dietary supplement for addressing oxidative stress and inflammation through its anti-inflammatory and prebiotic effects, which are conferred via the Nrf2/Keap1 pathway.

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Metabolomics of the Protective Effect of Ampelopsis grossedentata and Its Major Active Compound Dihydromyricetin on the Liver of High-Fat Diet Hamster.

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