Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids.
Excess triglyceride (TG) accumulation and increased fatty acid (FA) oxidation in the diabetic heart contribute to cardiac dysfunction. Punica granatum flower (PGF) is a traditional antidiabetic medicine. Here, we investigated the effects and mechanisms of action of PGF extract on abnormal cardiac lipid metabolism both in vivo and in vitro. Long-term oral administration of PGF extract (500 mg kg(-1)) reduced cardiac TG content, accompanied by a decrease in plasma levels of TG and total cholesterol in Zucker diabetic fatty (ZDF) rats, indicating improvement by PGF extract of abnormal cardiac TG accumulation and hyperlipidemia in this diabetic model. Treatment of ZDF rats with PGF extract lowered plasma FA levels. Furthermore, the treatment suppressed cardiac overexpression of mRNAs encoding for FA transport protein, peroxisome proliferator-activated receptor (PPAR)-alpha, carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase alpha2, and restored downregulated cardiac acetyl-CoA carboxylase mRNA expression in ZDF rats, whereas it showed little effect in Zucker lean rats. The results suggest that PGF extract inhibits increased cardiac FA uptake and oxidation in the diabetic condition. PGF extract and its component oleanolic acid enhanced PPAR-alpha luciferase reporter gene activity in human embryonic kidney 293 cells, and this effect was completely suppressed by a selective PPAR-alpha antagonist MK-886, consistent with the presence of PPAR-alpha activator activity in the extract and this component. Our findings suggest that PGF extract improves abnormal cardiac lipid metabolism in ZDF rats by activating PPAR-alpha and thereby lowering circulating lipid and inhibiting its cardiac uptake.
Huang
Tom Hsun-Wei
TH
Herbal Medicines Research and Education Centre, Faculty of Pharmacy, The University of Sydney, NSW, 2006, Australia.
Peng
Gang
G
Kota
Bhavani Prasad
BP
Li
George Qian
GQ
Yamahara
Johji
J
Roufogalis
Basil D
BD
Li
Yuhao
Y
D055372:AMP-Activated Protein Kinases; D042962:Acyl-CoA Oxidase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000032:analysis / Q000097:blood*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D050612:Fatty Acid Transport Proteins; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D035264:Flowers / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D029561:Lythraceae / Q000737:chemistry*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D047493:PPAR alpha / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D014280:Triglycerides / Q000032:analysis / Q000097:blood*
D050612:Fatty Acid Transport Proteins; D005230:Fatty Acids, Nonesterified; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes; D047493:PPAR alpha; D010936:Plant Extracts; D012333:RNA, Messenger; D014280:Triglycerides; D002784:Cholesterol; D042962:Acyl-CoA Oxidase; D002334:Carnitine O-Palmitoyltransferase; C526181:PRKAA2 protein, human; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases