Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 178, Issue -, Pages 108-115Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2019.05.083
Keywords
Chrysanthemum morifolium; Flavonoid; Diabetes; alpha-Glucosidase; PTP-1B signaling
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Funding
- National Natural Science Foundation of China [21502138]
- Natural Science Foundation of Tianjin [18JCYBJC94800]
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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.
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