Oroxin A from Oroxylum indicum prevents the progression from prediabetes to diabetes in streptozotocin and high-fat diet induced mice

Phytomedicine. 2018 Jan 1:38:24-34. doi: 10.1016/j.phymed.2017.10.003. Epub 2017 Oct 12.

Abstract

Background: Oroxylum indicum (L.) Kurz (Bignoniaceae) has been widely used for the treatment of respiratory infections and gastrointestinal disorders. Our previous study showed that an ethanol-water O. indicum seed extract (OISE), when combined with acarbose, reduced the risk of diabetes by 75% and effectively prevented the associated complications. Oroxin A, a major component of OISE, can activate PPARγ and inhibit α-glucosidase and it represents a promising candidate for diabetes intervention.

Purpose: The aim of this study is to investigate the effect of oroxin A from O. indicum on the progression of prediabetes to diabetes and the underlying mechanisms in streptozotocin and high-fat-diet induced prediabetic mice.

Methods: Oroxin A was purified from OISE and its PPARγ transcriptional activation was determined in vitro and in vivo. The prediabetic mice were established by high-fat diet and streptozotocin, which was followed by treatment with oroxin A. The effect of oroxin A was determined by analysis of the lipid profiles, oxidative stress, hepatic function and histology. The mechanism of oroxin A was also investigated.

Results: Oroxin A is a compound with low toxicity that has reduced the relative risk of progression from prediabetes to diabetes by 66.7% without inducing weight gain or hepatotoxicity. Oroxin A also improved the complications of prediabetes, such as lipid metabolism dysfunction and liver injury. Results of mechanism studies suggested that oroxin A is a partial PPARγ agonist that can activate PPARγ transcriptional activation in vitro and in vivo. Oroxin A also exhibited an inhibitory activity against α-glucosidase and an antioxidant capacity.

Conclusion: Oroxin A prevents the progression from prediabetes to diabetes through a multi-pathway intervention mechanism.

Keywords: Mechanism; Oroxin A; PPARγ; Prediabetes; Type 2 diabetes.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Bignoniaceae / chemistry
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / prevention & control*
  • Diet, High-Fat / adverse effects*
  • Flavones / pharmacology*
  • Glucosides / pharmacology*
  • Glycoside Hydrolase Inhibitors / pharmacology
  • Humans
  • Lipid Metabolism / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • PPAR gamma / metabolism
  • Prediabetic State / complications
  • Prediabetic State / drug therapy*
  • Prediabetic State / metabolism
  • Seeds / chemistry
  • Streptozocin / toxicity
  • alpha-Glucosidases

Substances

  • Antioxidants
  • Flavones
  • Glucosides
  • Glycoside Hydrolase Inhibitors
  • PPAR gamma
  • oroxin A
  • Streptozocin
  • alpha-Glucosidases