New insights into the biological activities of Chrysanthemum morifolium: Natural flavonoids alleviate diabetes by targeting α-glucosidase and the PTP-1B signaling pathway

被引:45
作者
Chen, Mingzhu [1 ]
Wang, Kaili [1 ]
Zhang, Yinan [1 ]
Zhang, Mengdi [1 ]
Ma, Yujiao [1 ]
Sun, Haifeng [1 ]
Jin, Zongxin [1 ]
Zheng, Hang [1 ]
Jiang, He [1 ]
Yu, Peng [1 ]
Zhang, Yongmin [1 ,2 ]
Sun, Hua [1 ]
机构
[1] Tianjin Univ Sci & Technol, China Int Sci & Technol Cooperat Base Food Nutr S, Minist Educ, Key Lab Ind Fermentat Microbiol, Tianjin 300457, Peoples R China
[2] Sorbonne Univ, Inst Parisien Chim Mol, UMR CNRS 8232, 4 Pl Jussieu, F-75005 Paris, France
基金
中国国家自然科学基金;
关键词
Chrysanthemum morifolium; Flavonoid; Diabetes; alpha-Glucosidase; PTP-1B signaling; IN-VITRO; SELECTIVITY;
D O I
10.1016/j.ejmech.2019.05.083
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
As dual regulators, the PTP-1B signaling pathway and alpha-glucosidase slow glucose release and increase the degree of insulin sensitivity, representing a promising therapeutic target for type 2 diabetes. In this study, we systematically examined the in vivo and in vitro anti-diabetic activities of natural flavonoids 1-6 from Chrysanthemum morifolium. Flavonoids 1-6 increased glucose consumption-promoting activity and the phosphorylation of GSK-3 beta and Akt, and decreased PTP-1B protein level along with slightly inhibitory activity of the PTP-1B enzyme. Moreover, flavonoids 1-2 treatment induced insulin secretion in INS-1 cells. Besides, in vivo study revealed that flavonoids 2 and 5 demonstrated potent anti hyperglycemic and anti-hyperlipidemic activity, and improved maltose and glucose tolerance. Although flavonoid 2 exhibited lower inhibitory activity against alpha-glucosidase in vitro, it could deglycosylated in vivo to diosmetin to function as an alpha-glucosidase inhibitor. Taken together, these results led to the identification of the natural flavonoids 1-6 from C. morifolium as dual regulators of alpha-glucosidase and the PTP-1B signaling pathway, suggesting their potential application as new oral anti-diabetic drugs or functional food ingredients. (C) 2019 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:108 / 115
页数:8
相关论文
共 21 条
[1]   Antitubercular activity of triterpenoids from Asteraceae flowers [J].
Akihisa, T ;
Franzblau, SG ;
Ukiya, M ;
Okuda, H ;
Zhang, FQ ;
Yasukawa, K ;
Suzuki, T ;
Kimura, Y .
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2005, 28 (01) :158-160
[2]   A flavanone and two phenolic acids from Chrysanthemum morifolium with phytotoxic and insect growth regulating activity [J].
Beninger, CW ;
Abou-Zaid, MM ;
Kistner, ALE ;
Hallett, RH ;
Iqbal, MJ ;
Grodzinski, B ;
Hall, JC .
JOURNAL OF CHEMICAL ECOLOGY, 2004, 30 (03) :589-606
[3]   Absorption and excretion of luteolin and apigenin in rats after oral administration of Chrysanthemum morifolium extract [J].
Chen, Ting ;
Li, Li-Ping ;
Lu, Xin-Yan ;
Jiang, Hui-Di ;
Zeng, Su .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2007, 55 (02) :273-277
[4]   Deglycosylation of Liquiritin Strongly Enhances its Inhibitory Potential Towards UDP-Glucuronosyltransferase (UGT) Isoforms [J].
Guo, Bin ;
Fan, Xu-Ran ;
Fang, Zhong-Ze ;
Cao, Yun-Feng ;
Hu, Cui-Min ;
Yang, Julin ;
Zhang, Yan-Yan ;
He, Rong-Rong ;
Zhu, Xu ;
Yu, Zhen-Wen ;
Sun, Xiao-Yu ;
Hong, Mo ;
Yang, Lu .
PHYTOTHERAPY RESEARCH, 2013, 27 (08) :1232-1236
[5]  
Guo Qiao-Sheng, 2008, Zhongguo Zhong Yao Za Zhi, V33, P756
[6]   Effects of total flavones from Dendranthema morifolium on vasocontraction and proliferation of vascular smooth muscle cells [J].
Jin, Hong-Feng ;
Liu, Xiao-Wei ;
Tang, Yi-Ming ;
Tang, Li-Jiang ;
Wang, Ya-Li ;
Du, Chang-Qing .
MOLECULAR MEDICINE REPORTS, 2016, 13 (01) :989-993
[7]   2,7"-Phloroglucinol-6,6′-bieckol protects INS-1 cells against high glucose-induced apoptosis [J].
Lee, Hyun-Ah ;
Lee, Ji-Hyeok ;
Han, Ji-Sook .
BIOMEDICINE & PHARMACOTHERAPY, 2018, 103 :1473-1481
[8]   Dieckol isolated from Ecklonia cava inhibits α-glucosidase and α-amylase in vitro and alleviates postprandial hyperglycemia in streptozotocin-induced diabetic mice [J].
Lee, Seung-Hong ;
Park, Mi-Hwa ;
Heo, Soo-Jin ;
Kang, Sung-Myung ;
Ko, Seok-Chun ;
Han, Ji-Sook ;
Jeon, You-Jin .
FOOD AND CHEMICAL TOXICOLOGY, 2010, 48 (10) :2633-2637
[9]   Chrysanthemum morifolium Ramat. reduces the oxidized LDL-induced expression of intercellular adhesion molecule-1 and E-selectin in human umbilical vein endothelial cells [J].
Lii, Chong-Kuei ;
Lei, Yen-Ping ;
Yao, Hsien-Tsung ;
Hsieh, Yun-Sheng ;
Tsai, Chia-Wen ;
Liu, Kai-Li ;
Chen, Haw-Wen .
JOURNAL OF ETHNOPHARMACOLOGY, 2010, 128 (01) :213-220
[10]   Identification of the phenolic components of chrysanthemum flower (Chrysanthemum morifolium Ramat) [J].
Lin, Long-Ze ;
Harnly, James M. .
FOOD CHEMISTRY, 2010, 120 (01) :319-326