Gravinol ameliorates high-fructose-induced metabolic syndrome through regulation of lipid metabolism and proinflammatory state in rats.
Using a rat model with fructose-induced metabolic syndrome, the effect of gravinol was investigated. Male Wistar rats were fed a 65% fructose diet and administered 10 or 20 mg of gravinol/kg of body weight/day for 2 weeks. High-level fructose feeding led to hyperglycemia, hyperlipidemia, hypertri-glyceridemia, and hypertension. On the other hand, the administration of gravinol significantly lowered serum glucose and total cholesterol levels. The tail arterial blood pressure was significantly elevated with the high-fructose diet. However, rats given gravinol showed a lower blood pressure as compared with fructose-fed control rats. In addition, the triglyceride (TG) levels in serum and lipoprotein fraction were dose-dependently reduced in rats fed gravinol. The decreases of hepatic TG and total cholesterol by gravinol were responsible for the down-regulation of hepatic sterol regulatory element binding protein (SREBP)-1. However, gravinol did not affect the protein levels of hepatic peroxisome proliferator-activated receptor-alpha and SREBP-2. Moreover, gravinol administration in the fructose-fed rats markedly reduced the glycosylated protein and thiobarbituric acid-reactive substance levels in the serum and hepatic mitochondria, and it inhibited the increase of the cyclooxygenase-2 protein level as a result of the down-regulation of nuclear factor kappa B (NF-kappaB). Furthermore, the decrease of anti-apoptotic bcl-2 protein levels and the increase of pro-apoptotic bax protein levels by the high-fructose diet were reversed by gravinol. These findings suggest that fructose-induced metabolic syndrome is attenuated by gravinol administration, which is associated with the reduction of serum lipids and protection against the proinflammatory state induced by oxidative stress.
Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. yokozawa@inm.u-toyama.ac.jp
Takako
T
Yokozawa
Hyun Ju
HJ
Kim
Eun Ju
EJ
Cho
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D005632:Fructose / Q000378:metabolism*; D056604:Grape Seed Extract; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D047493:PPAR alpha / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D047493:PPAR alpha; D010936:Plant Extracts; D044945:Proanthocyanidins; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D005632:Fructose