芦丁通过AMPK/SREBP1通路改善糖尿病性非酒精性脂肪性肝病的脂质代谢功能障碍。
Rutin ameliorated lipid metabolism dysfunction of diabetic NAFLD via AMPK/SREBP1 pathway.
作者信息
Liu Yadi, Sun Zhongyan, Dong Ruixue, Liu Peiyu, Zhang Xi, Li Yiran, Lai Xiaoshan, Cheong Hio-Fai, Wu Yuwei, Wang Yilin, Zhou Hua, Gui Dingkun, Xu Youhua
机构信息
Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao, PR China.
Faculty of Pharmacy, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao, PR China.
出版信息
Phytomedicine. 2024 Apr;126:155437. doi: 10.1016/j.phymed.2024.155437. Epub 2024 Feb 9.
BACKGROUND
In diabetic liver injury, nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. Rutin is a bioflavonoid produced by the hydrolysis of glucosidases to quercetin. Its biological activities include lowering blood glucose, regulating insulin secretion, regulating dyslipidemia, and exerting anti-inflammatory effects have been demonstrated. However, its effect on diabetic NAFLD is rarely reported.
PURPOSE
Our study aimed to investigate the protective effects of Rutin on diabetic NAFLD and potential pharmacological mechanism.
METHODS
We used db/db mice as the animal model to investigate diabetic NAFLD. Oleic acid-treated (OA) HeLa cells were examined whether Rutin had the ability to ameliorate lipid accumulation. HepG2 cells treated with 30 mM/l d-glucose and palmitic acid (PA) were used as diabetic NAFLD in vitro models. Total cholesterol (TC) and Triglycerides (TG) levels were determined. Oil red O staining and BODIPY 493/503 were used to detect lipid deposition within cells. The indicators of inflammation and oxidative stress were detected. The mechanism of Rutin in diabetic liver injury with NAFLD was analyzed using RNA-sequence and 16S rRNA, and the expression of fat-synthesizing proteins in the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway was investigated. Compound C inhibitors were used to further verify the relationship between AMPK and Rutin in diabetic NAFLD.
RESULTS
Rutin ameliorated lipid accumulation in OA-treated HeLa. In in vitro and in vivo models of diabetic NAFLD, Rutin alleviated lipid accumulation, inflammation, and oxidative stress. 16S analysis showed that Rutin could reduce gut microbiota dysregulation, such as the ratio of Firmicutes to Bacteroidetes. RNA-seq showed that the significantly differentially genes were mainly related to liver lipid metabolism. And the ameliorating effect of Rutin on diabetic NAFLD was through AMPK/SREBP1 pathway and the related lipid synthesis proteins was involved in this process.
CONCLUSION
Rutin ameliorated diabetic NAFLD by activating the AMPK pathway and Rutin might be a potential new drug ingredient for diabetic NAFLD.
背景
在糖尿病肝损伤中，非酒精性脂肪性肝病（NAFLD）是最常见的慢性肝病。芦丁是一种由糖苷酶水解生成槲皮素的生物类黄酮。其生物活性包括降低血糖、调节胰岛素分泌、调节血脂异常以及发挥抗炎作用。然而，其对糖尿病性NAFLD的影响鲜有报道。
目的
本研究旨在探讨芦丁对糖尿病性NAFLD的保护作用及潜在的药理机制。
方法
我们使用db/db小鼠作为动物模型来研究糖尿病性NAFLD。检测油酸处理（OA）的HeLa细胞中芦丁是否具有改善脂质积累的能力。用30 mM/l d-葡萄糖和棕榈酸（PA）处理的HepG2细胞作为体外糖尿病性NAFLD模型。测定总胆固醇（TC）和甘油三酯（TG）水平。采用油红O染色和BODIPY 493/503检测细胞内脂质沉积。检测炎症和氧化应激指标。利用RNA测序和16S rRNA分析芦丁在糖尿病合并NAFLD肝损伤中的作用机制，并研究5'腺苷单磷酸激活蛋白激酶（AMPK）途径中脂肪合成蛋白的表达。使用化合物C抑制剂进一步验证AMPK与芦丁在糖尿病性NAFLD中的关系。
结果
芦丁改善了OA处理的HeLa细胞中的脂质积累。在糖尿病性NAFLD的体外和体内模型中，芦丁减轻了脂质积累、炎症和氧化应激。16S分析表明，芦丁可以减少肠道微生物群失调，如厚壁菌门与拟杆菌门的比例。RNA测序显示，显著差异基因主要与肝脏脂质代谢有关。芦丁对糖尿病性NAFLD的改善作用是通过AMPK/SREBP1途径，相关的脂质合成蛋白参与了这一过程。
结论
芦丁通过激活AMPK途径改善糖尿病性NAFLD，芦丁可能是治疗糖尿病性NAFLD的一种潜在新药成分。
Zotero 插件