{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:59:24Z","timestamp":1787504364835,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T00:00:00Z","timestamp":1576108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>As one of the main marine carotenoids, fucoxanthin has strong antioxidant activity. FoxO3\u03b1, a member of the forkhead box O family of transcription factors, plays an important role in DN by regulating oxidative stress. The activity of FoxO3\u03b1 is related to its phosphorylation and acetylation status, regulated by Akt and Sirt1, a lysine deacetylase. Our study aimed to investigate whether fucoxanthin could alleviate oxidative stress and fibrosis via FoxO3\u03b1 in DN and whether Akt and Sirt1 were involved. We found that in GMCs cultured in HG, fucoxanthin treatment significantly reduced the expression of FN and collagen IV, as well as reactive oxygen species generation, suggesting that fucoxanthin is beneficial to alleviate both fibrosis and oxidative stress in DN. In addition, we found that fucoxanthin decreased the phosphorylation and acetylation level of FoxO3\u03b1, reversed the protein level of FoxO3\u03b1 inhibited by HG, and then promoted the nuclear transport of FoxO3\u03b1. Besides, fucoxanthin promoted the expression of manganese superoxide dismutase, a downstream target of FoxO3\u03b1. Furthermore, we found that fucoxanthin reversed the activation of Akt and inhibition of Sirt1. However, the enhancement of fucoxanthin in FoxO3\u03b1 expression and nuclear transport was significantly decreased by pretreatment with Akt activator SC79 or Sirt1 inhibitor EX527. In summary, our study explored fucoxanthin alleviated oxidative stress and fibrosis induced by HG through Akt\/Sirt1\/FoxO3\u03b1 signaling in GMCs, suggesting fucoxanthin is a potential therapeutic strategy for DN.<\/jats:p>","DOI":"10.3390\/md17120702","type":"journal-article","created":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T11:06:41Z","timestamp":1576148801000},"page":"702","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Fucoxanthin Alleviates Oxidative Stress through Akt\/Sirt1\/FoxO3\u03b1 Signaling to Inhibit HG-Induced Renal Fibrosis in GMCs"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1288-5809","authenticated-orcid":false,"given":"Guanyu","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou 570228, China"},{"name":"School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Jin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou 570228, China"},{"name":"School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxiao","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou 570228, China"},{"name":"School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoliang","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxuan","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1464-1883","authenticated-orcid":false,"given":"Xi","family":"Xie","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou 570228, China"},{"name":"School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrneph.2014.116","article-title":"Diabetic nephropathy\u2014Emerging epigenetic mechanisms","volume":"10","author":"Kato","year":"2014","journal-title":"Nat. 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