4.7 Article

Mulberry leaves ameliorate diabetes via regulating metabolic profiling and AGEs/RAGE and p38 MAPK/NF-κB pathway

期刊

JOURNAL OF ETHNOPHARMACOLOGY
卷 283, 期 -, 页码 -

出版社

ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2021.114713

关键词

Morus alba L; Diabetes mellitus; 1-deoxynojirimycin; Isoquercitrin; Glucose metabolism; Lipid metabolism; Insulin resistance

资金

  1. National Natural Science Foundation of China [81373889, 81473408, 81673533]
  2. National Administration of traditional Chinese Medicine Scientific Research Project of traditional Chinese Medicine Industry [201407002]
  3. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization [ZDXM-1-10]
  4. Construction Project for Jiangsu Key Lab-oratory for High Technology of TCM Formulae Research [BM2010576]
  5. Priority Academic Program Development of Jiangsu Higher Education Institutions [ysxk-2014]

向作者/读者索取更多资源

Alkaloids, flavonoids, and polysaccharides from mulberry leaves have been shown to significantly lower blood glucose and lipid levels by regulating glucose, amino acid, and lipid metabolism, while compounds like 1-DNJ and QG exhibit strong antidiabetic effects through various mechanisms in different cell types.
Ethnopharmacological relevance: Mulberry leaves have been used as traditional hypoglycemic medicine-food plant for thousand years in China. According to traditional Chinese medicine theory, type 2 diabetes mellitus (T2DM) belongs to the category of XiaoKe. Presently, the research of mulberry leaf hypoglycemic and lipid-lowering direction is mature, but the curative effects of alkaloids, flavonoids, polysaccharides, and other bioactive ingredients and the related mechanism is still unclear. Aim of the study: This paper aims to study the efficacy and mechanism of alkaloids, flavonoids, polysaccharides, and other bioactive components in mulberry leaves in the treatment of T2DM individually. Materials and methods: The determination of levels of fasting blood glucose (FBG), triglyceride (TG) and total cholesterol (T-Cho), and pyruvate kinase (PK), hexokinase (HK), and alanine aminotransferase (ALT/GPT) of in plasma of diabetic mice. Urine metabolomics was analyzed by UPLC-QTOF/MS to evaluate differential metabolites from multiple metabolic pathways. The glucose uptake of HepG2 cells and 3T3-L1 cells. Expression of Caspase-3 and caspase-9, inflammatory injury and p38MAPK/NF-Kappa B signaling pathway in GLUTag cells. Results: Our study revealed alkaloids, flavonoids, and polysaccharides in mulberry leaf could increase the levels of PK, HK, and ALT/GPT, and decrease the levels of TG and T-Cho significantly, and regulate glucose, amino acid, and lipid metabolism. Furthermore, 1-deoxynojirimycin (DNJ) and isoquercitrin (QG) both could increase glucose uptake and promote differentiation of HepG2 cells, increase PPAR gamma, C/EBP alpha and SREBP-l expression in 3T3-L1 cells, and inhibit AGEs-induced injury and apoptosis in GLUTag cells, reduce the expression of proteins related to AGEs/RAGE and p38MAPK/NF-Kappa B pathway. Notably, isoquercitrin exhibited more pronounced antidiabetic efficacy. Conclusions: The alkaloids, flavonoids, and polysaccharides from mulberry leaf exhibited hypoglycemic activity through the regulation of glucose, amino acid, and lipid metabolism. 1-DNJ and QG increased glucose uptake and promoted differentiation of HepG2 cells, increased PPAR gamma, C/EBP alpha and SREBP-l expression in 3T3-L1 cells, and inhibited AGEs-induced injury and apoptosis in GLUTag cells via the AGEs/RAGE and p38 MAPK/NF-Kappa B pathway.

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