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.
Yokozawa
Takako
T
Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. yokozawa@inm.u-toyama.ac.jp
Kim
Hyun Ju
HJ
Cho
Eun Ju
EJ
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