Young apple polyphenol extract prevents diabetic cognitive dysfunction by promoting TET2-mediated active DNA demethylation in the brain of diabetic mice
IntroductionDiabetic cognitive dysfunction (DCD) refers to the impairment of cognitive function resulting from diabetes. The increasing prevalence of diabetes and the aging population have rendered DCD a significant threat to brain health. Young apple polyphenol extract (YAPE) has demonstrated poten...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2025.1580775/full |
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| author | Jiacheng Fang Jiacheng Fang Xiaochen Zhang Zhongshi Qi Zhongshi Qi Liying Zhou Yuntiao Chen Qingxin Li Run Liu Hongzhuan Yu |
| author_facet | Jiacheng Fang Jiacheng Fang Xiaochen Zhang Zhongshi Qi Zhongshi Qi Liying Zhou Yuntiao Chen Qingxin Li Run Liu Hongzhuan Yu |
| author_sort | Jiacheng Fang |
| collection | DOAJ |
| description | IntroductionDiabetic cognitive dysfunction (DCD) refers to the impairment of cognitive function resulting from diabetes. The increasing prevalence of diabetes and the aging population have rendered DCD a significant threat to brain health. Young apple polyphenol extract (YAPE) has demonstrated potential in preventing DCD, although its underlying mechanism remains incompletely understood. Therefore, this study aims to investigate the preventive efficacy and underlying mechanisms of YAPE on DCD.MethodsStreptozotocin-induced diabetic mice were randomly divided into four groups (n = 15): the diabetes model group (DM), the metformin group (MET), the low-dose young apple polyphenol group (LYAP), and the high-dose young apple polyphenol group (HYAP). Meanwhile, 15 additional mice were assigned as the control group (CON).ResultsFollowing a 14-weeks intervention, disrupted cognitive function and neuronal apoptosis were observed in DM group, both of which were effectively restored by YAPE supplementation through improving ten-eleven translocation protein 2 (TET2)-mediated active DNA demethylation. Moreover, YAPE supplementation enhanced TET2 protein stability by activating phosphorylated AMP-activated protein kinase (AMPK) and improved TET enzyme activity by upregulating α-ketoglutarate/(succinic acid + fumaric acid) ratio, subsequently enhancing TET2 function.DiscussionConsequently, YAPE effectively delays progression from diabetes to DCD by facilitating TET2-mediated active DNA demethylation. |
| format | Article |
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| institution | OA Journals |
| issn | 2296-861X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Nutrition |
| spelling | doaj-art-3ec99c3ecb584e2db0e9668f03e4215e2025-08-20T01:48:03ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2025-05-011210.3389/fnut.2025.15807751580775Young apple polyphenol extract prevents diabetic cognitive dysfunction by promoting TET2-mediated active DNA demethylation in the brain of diabetic miceJiacheng Fang0Jiacheng Fang1Xiaochen Zhang2Zhongshi Qi3Zhongshi Qi4Liying Zhou5Yuntiao Chen6Qingxin Li7Run Liu8Hongzhuan Yu9Weifang Hospital of Traditional Medicine, Affiliated Traditional Chinese Medicine of Shandong Second Medical University, Weifang, Shandong, ChinaSchool of Public Health, Qingdao University, Qingdao, Shandong, ChinaDepartment of International Management, Business School, The University of Adelaide, Adelaide, SA, AustraliaSchool of Public Health, Qingdao University, Qingdao, Shandong, ChinaCenter for Disease Control and Prevention of Tangshan City, Tangshan, Hebei, ChinaSchool of Public Health, Qingdao University, Qingdao, Shandong, ChinaSchool of Public Health, Qingdao University, Qingdao, Shandong, ChinaSchool of Public Health, Qingdao University, Qingdao, Shandong, ChinaSchool of Public Health, Qingdao University, Qingdao, Shandong, ChinaWeifang Hospital of Traditional Medicine, Affiliated Traditional Chinese Medicine of Shandong Second Medical University, Weifang, Shandong, ChinaIntroductionDiabetic cognitive dysfunction (DCD) refers to the impairment of cognitive function resulting from diabetes. The increasing prevalence of diabetes and the aging population have rendered DCD a significant threat to brain health. Young apple polyphenol extract (YAPE) has demonstrated potential in preventing DCD, although its underlying mechanism remains incompletely understood. Therefore, this study aims to investigate the preventive efficacy and underlying mechanisms of YAPE on DCD.MethodsStreptozotocin-induced diabetic mice were randomly divided into four groups (n = 15): the diabetes model group (DM), the metformin group (MET), the low-dose young apple polyphenol group (LYAP), and the high-dose young apple polyphenol group (HYAP). Meanwhile, 15 additional mice were assigned as the control group (CON).ResultsFollowing a 14-weeks intervention, disrupted cognitive function and neuronal apoptosis were observed in DM group, both of which were effectively restored by YAPE supplementation through improving ten-eleven translocation protein 2 (TET2)-mediated active DNA demethylation. Moreover, YAPE supplementation enhanced TET2 protein stability by activating phosphorylated AMP-activated protein kinase (AMPK) and improved TET enzyme activity by upregulating α-ketoglutarate/(succinic acid + fumaric acid) ratio, subsequently enhancing TET2 function.DiscussionConsequently, YAPE effectively delays progression from diabetes to DCD by facilitating TET2-mediated active DNA demethylation.https://www.frontiersin.org/articles/10.3389/fnut.2025.1580775/fulldiabetic cognitive dysfunctionactive DNA demethylationten-eleven translocation protein 2young apple polyphenol extractmitochondrion |
| spellingShingle | Jiacheng Fang Jiacheng Fang Xiaochen Zhang Zhongshi Qi Zhongshi Qi Liying Zhou Yuntiao Chen Qingxin Li Run Liu Hongzhuan Yu Young apple polyphenol extract prevents diabetic cognitive dysfunction by promoting TET2-mediated active DNA demethylation in the brain of diabetic mice Frontiers in Nutrition diabetic cognitive dysfunction active DNA demethylation ten-eleven translocation protein 2 young apple polyphenol extract mitochondrion |
| title | Young apple polyphenol extract prevents diabetic cognitive dysfunction by promoting TET2-mediated active DNA demethylation in the brain of diabetic mice |
| title_full | Young apple polyphenol extract prevents diabetic cognitive dysfunction by promoting TET2-mediated active DNA demethylation in the brain of diabetic mice |
| title_fullStr | Young apple polyphenol extract prevents diabetic cognitive dysfunction by promoting TET2-mediated active DNA demethylation in the brain of diabetic mice |
| title_full_unstemmed | Young apple polyphenol extract prevents diabetic cognitive dysfunction by promoting TET2-mediated active DNA demethylation in the brain of diabetic mice |
| title_short | Young apple polyphenol extract prevents diabetic cognitive dysfunction by promoting TET2-mediated active DNA demethylation in the brain of diabetic mice |
| title_sort | young apple polyphenol extract prevents diabetic cognitive dysfunction by promoting tet2 mediated active dna demethylation in the brain of diabetic mice |
| topic | diabetic cognitive dysfunction active DNA demethylation ten-eleven translocation protein 2 young apple polyphenol extract mitochondrion |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2025.1580775/full |
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