Anti-diabetic action of Punica granatum flower extract:: Activation of PPAR-γ and identification of an active component

被引:202
作者
Huang, THW
Peng, G
Kota, BP
Li, GQ
Yamahara, J
Roufogalis, BD
Li, YH
机构
[1] Univ Sydney, Fac Pharm, Herbal Med Res & Educ Ctr, Sydney, NSW 2006, Australia
[2] Pharm Food Inst, Kyoto, Japan
关键词
Punica granatum; gallic acid; diabetes; hyperglycemia; PPAR-gamma; Zucker diabetic fatty rats;
D O I
10.1016/j.taap.2004.12.009
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Peroxisome proliferator-activated receptor (PPAR)-gamma activators are widely used in the treatment of type 2 diabetes because they improve the sensitivity of insulin receptors. Punica granatum flower (PGF) has been used as an anti-diabetic medicine in Unani medicinal literature. The mechanism of actions is, however, unknown. In the current study, we demonstrated that 6-week oral administration of methanol extract from PGF (500 mg/kg, daily) inhibited glucose loading-induced increase of plasma glucose levels in Zucker diabetic fatty rats (ZDF), a genetic animal model for type 2 diabetes, whereas it did not inhibit the increase in Zucker lean rats (ZL). The treatment did not lower the plasma glucose levels in fasted ZDF and ZL rats. Furthermore, RT-PCR results demonstrated that the PGF extract treatment in ZDF rats enhanced cardiac PPAR-gamma mRNA expression and restored the down-regulated cardiac glucose transporter (GLUT)-4 (the insulin-dependent isoform of GLUTs) mRNA. These results suggest that the anti-diabetic activity of PGF extract may result from improved sensitivity of the insulin receptor. From the in vitro studies, we demonstrated that the PGF extract enhanced PPAR-gamma mRNA and protein expression and increased PPAR-gamma-dependent mRNA expression and activity of lipoprotein lipase in human THP-1-differentiated macrophage cells. Phytochemical investigation demonstrated that gallic acid in PGF extract is mostly responsible for this activity. Thus, our findings indicate that PPAR-gamma is a molecular target for PGF extract and its prominent component gallic acid, and provide a better understanding of the potential mechanism of the anti-diabetic action of PGF. (c) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:160 / 169
页数:10
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