Journal
PHYTOMEDICINE
Volume 38, Issue -, Pages 24-34Publisher
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.phymed.2017.10.003
Keywords
Oroxin A; Prediabetes; Type 2 diabetes; PPAR gamma; Mechanism
Categories
Funding
- National Natural Science Foundation of China [81172966]
- Important National Science & Technology Specific Projects of Novel Drug Discovery of the PR China [2010ZX09401-403, 2012ZX09301002-003]
- Fundamental Research Funds for the Central Universities [DUT12ZD209]
- Open Fund of Key Laboratory of Biotechnology and Bioresources Utilization (Dalian Minzu University), China
- State Ethnic Affairs Commission, China
- Ministry of Education, China
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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 PPAR. and inhibit a-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 PPAR. 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 PPAR. agonist that can activate PPAR. transcriptional activation in vitro and in vivo. Oroxin A also exhibited an inhibitory activity against a-glucosidase and an antioxidant capacity. Conclusion: Oroxin A prevents the progression from prediabetes to diabetes through a multi-pathway intervention mechanism.
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