Anti-diabetic action of Punica granatum flower extract: activation of PPAR-gamma and identification of an active component.
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.
Huang
Tom H W
TH
Herbal Medicines Research and Education Centre, The University of Sydney, NSW 2006 Australia.
Peng
Gang
G
Kota
Bhavani P
BP
Li
George Q
GQ
Yamahara
Johji
J
Roufogalis
Basil D
BD
Li
Yuhao
Y
D000818:Animals; D035264:Flowers / Q000737:chemistry*; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D029561:Lythraceae / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D009124:Muscle Proteins / Q000032:analysis; D047495:PPAR gamma / Q000187:drug effects* / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker
D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D047495:PPAR gamma; D010936:Plant Extracts; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat