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Hypoglycemic Effect of Nobiletin via Regulation of Islet β-Cell Mitophagy and Gut Microbiota Homeostasis in Streptozocin-Challenged Mice
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-05-06 , DOI: 10.1021/acs.jafc.2c00148 Sijie Yuan 1, 2 , Zichong Ye 2 , Ye Li 1 , Jiaxuan Zou 3 , Mengting Wu 2 , Ke Wang 4 , Wenzhen Liao 2 , Jie Shen 1
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-05-06 , DOI: 10.1021/acs.jafc.2c00148 Sijie Yuan 1, 2 , Zichong Ye 2 , Ye Li 1 , Jiaxuan Zou 3 , Mengting Wu 2 , Ke Wang 4 , Wenzhen Liao 2 , Jie Shen 1
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Nobiletin is a natural nutrient (or polymethoxyflavonoid) in orange peels exerting a preventive effect against metabolic diseases. However, there are very few reports on the hypoglycemic effect of nobiletin. In the present study, the hypoglycemic effect of nobiletin was investigated using NIT-1 cells and streptozocin (STZ)-challenged mouse models. Our results indicated that nobiletin could significantly suppress the high blood glucose in STZ-challenged mice. In addition, nobiletin could effectively activate the mitophagy and inhibit the inflammatory pathways in NIT-1 cells. The mitochondria membrane potential dysbiosis induced by glucotoxicity in NIT-1 cells was restored after treatment by nobiletin. Further investigation revealed that the hypoglycemic effect of nobiletin was mainly through regulation of gut microbiota dysbiosis, activation of mitophagy flux, inhibition of inflammasome expression, and restoration of islet morphological destruction in the pancreas of STZ-challenged mice. Our study revealed that nobiletin could be used as a functional food or drug candidate for the treatment of diabetes.
中文翻译：
Nobiletin 通过调节链脲佐菌素攻击小鼠的胰岛 β 细胞线粒体自噬和肠道微生物群稳态的降血糖作用
Nobiletin 是橙皮中的天然营养素（或多甲氧基黄酮），对代谢疾病具有预防作用。然而，关于诺比列汀降血糖作用的报道很少。在本研究中，使用 NIT-1 细胞和链脲佐菌素 (STZ) 攻击的小鼠模型研究了 nobiletin 的降血糖作用。我们的结果表明，nobiletin 可以显着抑制 STZ 攻击小鼠的高血糖。此外，nobiletin可有效激活线粒体自噬，抑制NIT-1细胞的炎症通路。NIT-1 细胞中由糖毒性引起的线粒体膜电位失调在 nobiletin 处理后得到恢复。进一步研究表明，川崎降糖作用主要是通过调节肠道菌群失调，STZ 攻击小鼠胰腺中线粒体自噬通量的激活、炎性体表达的抑制和胰岛形态破坏的恢复。我们的研究表明，nobiletin 可用作治疗糖尿病的功能性食品或药物候选物。
更新日期：2022-05-06
中文翻译：
Nobiletin 通过调节链脲佐菌素攻击小鼠的胰岛 β 细胞线粒体自噬和肠道微生物群稳态的降血糖作用
Nobiletin 是橙皮中的天然营养素（或多甲氧基黄酮），对代谢疾病具有预防作用。然而，关于诺比列汀降血糖作用的报道很少。在本研究中，使用 NIT-1 细胞和链脲佐菌素 (STZ) 攻击的小鼠模型研究了 nobiletin 的降血糖作用。我们的结果表明，nobiletin 可以显着抑制 STZ 攻击小鼠的高血糖。此外，nobiletin可有效激活线粒体自噬，抑制NIT-1细胞的炎症通路。NIT-1 细胞中由糖毒性引起的线粒体膜电位失调在 nobiletin 处理后得到恢复。进一步研究表明，川崎降糖作用主要是通过调节肠道菌群失调，STZ 攻击小鼠胰腺中线粒体自噬通量的激活、炎性体表达的抑制和胰岛形态破坏的恢复。我们的研究表明，nobiletin 可用作治疗糖尿病的功能性食品或药物候选物。
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