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白杨素通过调节高脂饮食/链脲佐菌素诱导的糖尿病肾病小鼠中AMPK介导的脂质代谢来改善糖尿病肾病。

Chrysin improves diabetic nephropathy by regulating the AMPK-mediated lipid metabolism in HFD/STZ-induced DN mice.

作者信息

Zhou Yingjun, Tao Heng, Xu Nuo, Zhou Shichun, Peng Yuke, Zhu Jianxiang, Liu Shaowei, Chang Yaning

机构信息

The State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, Shanghai, People's Republic of China.

Agricultural and Rural Bureau, Haiyang, Shandong, People's Republic of China.

出版信息

J Food Biochem. 2022 Dec;46(12):e14379. doi: 10.1111/jfbc.14379. Epub 2022 Aug 17.

DOI:10.1111/jfbc.14379
PMID:35976957
Abstract

Diabetic nephropathy (DN) is a highly prevalent and severe diabetic complication. It is urgent to explore high efficiency and minor side effects therapy for DN. Chrysin is a natural flavonoid with various biological activities found in honey and propolis, and has considerable potential to improve DN. The study was designed to explore the effects and the specific underlying mechanism of chrysin for DN in high-fat-diet (HFD) and streptozotocin (STZ) induced DN mice. Firstly, the study revealed that chrysin effectively improved obesity, insulin resistance (IR), renal function, and pathological injury in DN mice. Secondly, the study found that chrysin improved the key indices and markers of lipid accumulation, oxidative stress, and inflammation which are closely related to the development or progression of DN. Moreover, chrysin markedly modulated lipid metabolism by regulating Adenosine 5' monophosphate-activated protein kinase (AMPK) and essential downstream proteins. Furthermore, AMPK inhibitor (Dorsomorphin) intervention partially suppressed the positive effects of chrysin on all testing indicators, indicating that activated AMPK is crucial for chrysin action on DN. The present study demonstrated that chrysin may improve DN by regulating lipid metabolism, and activated AMPK plays a critical role in the regulation of chrysin. PRACTICAL APPLICATIONS: The study verified the positive effects of chrysin on obesity, insulin resistance, kidney injury, renal function, lipid accumulation, inflammation, and oxidative stress, which are closely related to the development or progression of diabetic nephropathy (DN). Moreover, we explored that chrysin improves DN by regulating AMPK-mediated lipid metabolism. Furthermore, the AMPK inhibitor was used to confirm that activated AMPK plays a critical role in the effects of chrysin. These results could offer a full explanation and a potential option for adjuvant therapy of DN diabetes with chrysin.

摘要

糖尿病肾病(DN)是一种高度普遍且严重的糖尿病并发症。探索高效且副作用小的DN治疗方法迫在眉睫。白杨素是一种存在于蜂蜜和蜂胶中的具有多种生物活性的天然黄酮类化合物,在改善DN方面具有相当大的潜力。本研究旨在探讨白杨素对高脂饮食(HFD)和链脲佐菌素(STZ)诱导的DN小鼠的影响及其具体潜在机制。首先,研究表明白杨素能有效改善DN小鼠的肥胖、胰岛素抵抗(IR)、肾功能和病理损伤。其次,研究发现白杨素改善了与DN发生或发展密切相关的脂质蓄积、氧化应激和炎症的关键指标及标志物。此外,白杨素通过调节腺苷酸活化蛋白激酶(AMPK)及其重要的下游蛋白显著调节脂质代谢。此外,AMPK抑制剂( dorsomorphin)干预部分抑制了白杨素对所有检测指标的积极作用,表明激活的AMPK对白杨素改善DN的作用至关重要。本研究表明,白杨素可能通过调节脂质代谢来改善DN,而激活的AMPK在白杨素的调节中起关键作用。实际应用:该研究证实了白杨素对肥胖、胰岛素抵抗、肾损伤、肾功能、脂质蓄积、炎症和氧化应激具有积极作用,这些均与糖尿病肾病(DN)的发生或发展密切相关。此外,我们探究了白杨素通过调节AMPK介导的脂质代谢来改善DN。此外,使用AMPK抑制剂证实激活的AMPK在白杨素的作用中起关键作用。这些结果可为白杨素辅助治疗DN糖尿病提供全面解释和潜在选择。

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