Mechanism of Flavonoids from Mulberry Leaves on Insulin Resistance and Inflammatory Response in Diabetic Mice

XU Guangyuan; ZHANG Xiaoming; JIA Chunling

doi:10.13422/j.cnki.syfjx.20231422

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Mechanism of Flavonoids from Mulberry Leaves on Insulin Resistance and Inflammatory Response in Diabetic Mice

更新时间：2023-07-18

- Mechanism of Flavonoids from Mulberry Leaves on Insulin Resistance and Inflammatory Response in Diabetic Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 16, Pages: 52-57(2023)
- 作者机构：
  
  首都医科大学附属复兴医院，北京 100045
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20231422
  CLC： R2-0;R22;R242;R2-031;R285.5
- Published：20 August 2023，
  
  Published Online：14 June 2023，
  
  Received：02 April 2023，
- 稿件说明：
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许光远,张晓明,贾春玲.桑叶黄酮对糖尿病小鼠胰岛素抵抗及炎症反应的作用机制[J].中国实验方剂学杂志,2023,29(16):52-57.

XU Guangyuan,ZHANG Xiaoming,JIA Chunling.Mechanism of Flavonoids from Mulberry Leaves on Insulin Resistance and Inflammatory Response in Diabetic Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(16):52-57.
许光远,张晓明,贾春玲.桑叶黄酮对糖尿病小鼠胰岛素抵抗及炎症反应的作用机制[J].中国实验方剂学杂志,2023,29(16):52-57. DOI： 10.13422/j.cnki.syfjx.20231422.

XU Guangyuan,ZHANG Xiaoming,JIA Chunling.Mechanism of Flavonoids from Mulberry Leaves on Insulin Resistance and Inflammatory Response in Diabetic Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(16):52-57. DOI： 10.13422/j.cnki.syfjx.20231422.

摘要

目的

观察桑叶黄酮降糖、改善胰岛素抵抗、抗炎作用并探讨其作用机制。

方法

6~7周龄雄性db/db小鼠随机分为模型组、桑叶黄酮高、低剂量组（1.00、0.50 g·kg

-1

·d

-1

），另设同周龄C57BL小鼠为正常组。干预6周后，检测小鼠空腹血糖（FBG）、血清胰岛素水平（Fins）、白细胞介素-6（IL-6）、肿瘤坏死因子-

（TNF-

）、游离脂肪酸（FFA）、血肌酐（SCr）、血尿素氮（BUN）、天门冬氨酸氨基转移酶（AST）、计算胰岛素抵抗指数（HOMA-IR）；检测肝脏超氧化物歧化酶（SOD）、谷胱甘肽过氧物酶（GSH-Px）、过氧化氢酶（Catalase）；苏木素-伊红（HE）染色检测小鼠肝脏形态结构变化；蛋白免疫印迹法（Western blot）检测肝脏环氧合酶-2（COX-2）、一氧化氮合酶（iNOS）、核转录因子-

B（NF-

B）蛋白表达。

结果

与模型组比较，桑叶黄酮高、低剂量组FBG、Fins、HOMA-IR、IL-6、TNF-

、FFA水平明显降低（

0.05，

0.01）；肝脏SOD、GSH-Px、Catalase水平明显升高（

0.05，

0.01）；与模型组比较，桑叶黄酮高、低剂量组HE染色显示肝细胞排列整齐，炎细胞浸润及细胞脂肪样变明显改善；与模型组比较，桑叶黄酮高、低剂量组肝脏COX-2、iNOS、NF-

B蛋白表达明显降低（

0.05，

0.01）。

结论

桑叶黄酮具有降糖、改善胰岛素抵抗作用，其作用可能是通过调控糖尿病小鼠肝脏NF-

B分子影响COX-2、iNOS及炎症因子释放，改善炎症状态实现的。

Abstract

Objective

To observe the glucose-lowering， insulin resistance-improving， and anti-inflammatory effects of flavonoids from mulberry leaves （FML） and explore their underlying mechanism.

Method

Male db/db mice aged 6-7 weeks were randomly divided into a model group， a high-dose FML group （1.00 g·kg·d

-1

）， and a low-dose FML group （0.50 g·kg

-1

·d

-1

）. C57BL mice of the same age were assigned to the normal group. After six weeks of intervention， fasting blood glucose （FBG）， serum fasting insulin levels （Fins）， interleukin-6 （IL-6）， tumor necrosis factor-

（TNF-

）， free fatty acid （FFA）， blood creatinine （SCr）， blood urea nitrogen （BUN）， and aspartate aminotransferase （AST） levels were measured， and the homeostasis model assessment of insulin resistance （HOMA-IR） was calculated. Superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and catalase activities in the liver were measured. Morphological changes in the liver were assessed by hematoxylin-eosin （HE） staining. The protein expression of cyclooxygenase-2 （COX-2）， inducible nitric oxide synthase （iNOS）， and nuclear factor-

B （NF-

B） in the liver was detected by Western blot.

Result

Compared with the model group， the high-dose and low-dose FML groups showed significant reductions in FBG， Fins， HOMA-IR， IL-6， TNF-

， and FFA levels （

0.05，

0.01）， and increased levels of SOD， GSH-Px， and catalase in the liver （

0.05，

0.01）. HE staining of the liver in the FML groups showed improved arrangement of hepatocytes， reduced inflammatory cell infiltration， and alleviated cellular steatosis compared with the model group. The protein expression of COX-2， iNOS， and NF-

B in the liver significantly decreased in the FML groups as compared with that in the model group （

0.05，

0.01）.

Conclusion

FML have glucose-lowering and insulin resistance-improving effect， which may be attributed to their regulation of the NF-

B pathway in the liver of diabetic mice， leading to the suppression of the release of COX-2， iNOS， and inflammatory cytokines， thereby improving the inflammatory state.

关键词

桑叶黄酮2型糖尿病胰岛素抵抗炎症环氧合酶-2（COX-2）一氧化氮合酶（iNOS）核转录因子-κB（NF-κB）

Keywords

flavonoids from mulberry leavestype 2 diabetesinsulin resistanceinflammationcyclooxygenase-2（COX-2）inducible nitric oxide synthase（iNOS）nuclear factor-κB （NF-κB）

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