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.