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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.<\/jats:p>","DOI":"10.3390\/antiox12030547","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T03:59:16Z","timestamp":1677038356000},"page":"547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The Water Extract of Ampelopsis grossedentata Alleviates Oxidative Stress and Intestinal Inflammation"],"prefix":"10.3390","volume":"12","author":[{"given":"Zhaojie","family":"Wang","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7840-0210","authenticated-orcid":false,"given":"Qian","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"Hunan Qiankun Biological Technology Co., Ltd., Zhangjiajie 427000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenmao","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan Qiankun Biological Technology Co., Ltd., Zhangjiajie 427000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China"},{"name":"Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7094","DOI":"10.1038\/s41467-021-27428-9","article-title":"Oxidative stress-induced FABP5 S-glutathionylation protects against acute lung injury by suppressing inflammation in macrophages","volume":"12","author":"Guo","year":"2021","journal-title":"Nat. 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