Antidiabetic-Like Effects of Naringenin-7-O-glucoside from Edible Chrysanthemum 'Kotobuki' and Naringenin by Activation of the PI3K/Akt Pathway and PPARγ

Chem Biodivers. 2019 Jan;16(1):e1800434. doi: 10.1002/cbdv.201800434. Epub 2018 Dec 10.

Abstract

Obesity is directly associated with cancer, cardiovascular injury, hypertension, and type 2 diabetes. To date, Yamamoto identified that hot water extracts of edible Chrysanthemum (EC) induced cell size reduction, up-regulation of adiponectin expression, and glucose absorption inhibition in 3T3-L1 cells during adipocyte differentiation. Furthermore, EC showed antidiabetic effects such as improvement in insulin resistance and the down-regulation of the blood glucose level and liver lipid content in type 2 diabetes model mice. In this study, we attempted to identify the antidiabetic components in EC. The methanol fraction from EC that showed relatively strong biological activity was purified by chromatography to obtain acacetin-7-O-glucoside, apigenin-7-O-glucoside, kaempferol-7-O-glucoside, and naringenin-7-O-glucoside. Among the isolated compounds and their aglycones, naringenin (NA) and naringenin-7-O-glucoside (NAG) up-regulated the intracellular accumulation of lipid and adiponectin-secretion and down-regulated the diameter of 3T3-L1 cells during adipocyte differentiation. Because the PPARγ antagonist BADGE and PI3K/Akt inhibitors wortmannin and LY29004 inhibited the intracellular lipid accumulation by NA and NAG associated with adipogenesis, it was considered that NA and NAG showed the above-mentioned activities via the activation of PPARγ as well as phosphorylation of the PI3K/Akt pathway.

Keywords: Akt; Chrysanthemum morifolium; adipogenesis; biological activity; lipogenesis; lipolysis; peroxisome proliferator activated receptor γ.

MeSH terms

  • 3T3-L1 Cells
  • Adipogenesis / drug effects
  • Animals
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Chrysanthemum / chemistry*
  • Enzyme Activation
  • Flavanones / isolation & purification
  • Flavanones / pharmacology*
  • Glucosides / isolation & purification
  • Glucosides / pharmacology*
  • Hypoglycemic Agents / isolation & purification
  • Hypoglycemic Agents / pharmacology*
  • Lipid Metabolism / drug effects
  • Mice
  • PPAR gamma / agonists*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Plant Extracts / pharmacology*
  • Plants, Edible / chemistry*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects

Substances

  • Flavanones
  • Glucosides
  • Hypoglycemic Agents
  • PPAR gamma
  • Phosphoinositide-3 Kinase Inhibitors
  • Plant Extracts
  • naringenin-7-O-glucoside
  • Proto-Oncogene Proteins c-akt
  • naringenin