The protective roles of eugenol on type 1 diabetes mellitus through NRF2-mediated oxidative stress pathway
Type 1 diabetes mellitus (T1DM), known as insulin-dependent diabetes mellitus, is characterized by persistent hyperglycemia resulting from damage to the pancreatic β cells and an absolute deficiency of insulin, leading to multi-organ involvement and a poor prognosis. The progression of T1DM is signi...
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eLife Sciences Publications Ltd
2025-01-01
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author | Yalan Jiang Pingping He Ke Sheng Yongmiao Peng Huilan Wu Songwei Qian Weiping Ji Xiaoling Guo Xiaoou Shan |
author_facet | Yalan Jiang Pingping He Ke Sheng Yongmiao Peng Huilan Wu Songwei Qian Weiping Ji Xiaoling Guo Xiaoou Shan |
author_sort | Yalan Jiang |
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description | Type 1 diabetes mellitus (T1DM), known as insulin-dependent diabetes mellitus, is characterized by persistent hyperglycemia resulting from damage to the pancreatic β cells and an absolute deficiency of insulin, leading to multi-organ involvement and a poor prognosis. The progression of T1DM is significantly influenced by oxidative stress and apoptosis. The natural compound eugenol (EUG) possesses anti-inflammatory, anti-oxidant, and anti-apoptotic properties. However, the potential effects of EUG on T1DM had not been investigated. In this study, we established the streptozotocin (STZ)-induced T1DM mouse model in vivo and STZ-induced pancreatic β cell MIN6 cell model in vitro to investigate the protective effects of EUG on T1DM, and tried to elucidate its potential mechanism. Our findings demonstrated that the intervention of EUG could effectively induce the activation of nuclear factor E2-related factor 2 (NRF2), leading to an up-regulation in the expressions of downstream proteins NQO1 and HMOX1, which are regulated by NRF2. Moreover, this intervention exhibited a significant amelioration in pancreatic β cell damage associated with T1DM, accompanied by an elevation in insulin secretion and a reduction in the expression levels of apoptosis and oxidative stress-related markers. Furthermore, ML385, an NRF2 inhibitor, reversed these effects of EUG. The present study suggested that EUG exerted protective effects on pancreatic β cells in T1DM by attenuating apoptosis and oxidative stress through the activation of the NRF2 signaling pathway. Consequently, EUG holds great promise as a potential therapeutic candidate for T1DM. |
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spelling | doaj-art-63a97fc3aee84df0bab104893a97cf402025-01-23T09:59:21ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.96600The protective roles of eugenol on type 1 diabetes mellitus through NRF2-mediated oxidative stress pathwayYalan Jiang0Pingping He1Ke Sheng2Yongmiao Peng3Huilan Wu4Songwei Qian5Weiping Ji6Xiaoling Guo7https://orcid.org/0000-0003-3153-6249Xiaoou Shan8https://orcid.org/0009-0009-0487-9474Department of Pediatrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaBasic Medical Research Center, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaBasic Medical Research Center, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaBasic Medical Research Center, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Genaral Surgery, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, China; Department of General Surgery, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Genaral Surgery, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, China; Department of General Surgery, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China; Basic Medical Research Center, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Children Genitourinary Diseases of Wenzhou, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pediatrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Children Genitourinary Diseases of Wenzhou, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaType 1 diabetes mellitus (T1DM), known as insulin-dependent diabetes mellitus, is characterized by persistent hyperglycemia resulting from damage to the pancreatic β cells and an absolute deficiency of insulin, leading to multi-organ involvement and a poor prognosis. The progression of T1DM is significantly influenced by oxidative stress and apoptosis. The natural compound eugenol (EUG) possesses anti-inflammatory, anti-oxidant, and anti-apoptotic properties. However, the potential effects of EUG on T1DM had not been investigated. In this study, we established the streptozotocin (STZ)-induced T1DM mouse model in vivo and STZ-induced pancreatic β cell MIN6 cell model in vitro to investigate the protective effects of EUG on T1DM, and tried to elucidate its potential mechanism. Our findings demonstrated that the intervention of EUG could effectively induce the activation of nuclear factor E2-related factor 2 (NRF2), leading to an up-regulation in the expressions of downstream proteins NQO1 and HMOX1, which are regulated by NRF2. Moreover, this intervention exhibited a significant amelioration in pancreatic β cell damage associated with T1DM, accompanied by an elevation in insulin secretion and a reduction in the expression levels of apoptosis and oxidative stress-related markers. Furthermore, ML385, an NRF2 inhibitor, reversed these effects of EUG. The present study suggested that EUG exerted protective effects on pancreatic β cells in T1DM by attenuating apoptosis and oxidative stress through the activation of the NRF2 signaling pathway. Consequently, EUG holds great promise as a potential therapeutic candidate for T1DM.https://elifesciences.org/articles/96600pancreatic β celltype 1 diabetes mellituseugenolNRF2 signaling pathwayapoptosisoxidative stress |
spellingShingle | Yalan Jiang Pingping He Ke Sheng Yongmiao Peng Huilan Wu Songwei Qian Weiping Ji Xiaoling Guo Xiaoou Shan The protective roles of eugenol on type 1 diabetes mellitus through NRF2-mediated oxidative stress pathway eLife pancreatic β cell type 1 diabetes mellitus eugenol NRF2 signaling pathway apoptosis oxidative stress |
title | The protective roles of eugenol on type 1 diabetes mellitus through NRF2-mediated oxidative stress pathway |
title_full | The protective roles of eugenol on type 1 diabetes mellitus through NRF2-mediated oxidative stress pathway |
title_fullStr | The protective roles of eugenol on type 1 diabetes mellitus through NRF2-mediated oxidative stress pathway |
title_full_unstemmed | The protective roles of eugenol on type 1 diabetes mellitus through NRF2-mediated oxidative stress pathway |
title_short | The protective roles of eugenol on type 1 diabetes mellitus through NRF2-mediated oxidative stress pathway |
title_sort | protective roles of eugenol on type 1 diabetes mellitus through nrf2 mediated oxidative stress pathway |
topic | pancreatic β cell type 1 diabetes mellitus eugenol NRF2 signaling pathway apoptosis oxidative stress |
url | https://elifesciences.org/articles/96600 |
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