Ibrolipim (NO-1886) attenuates high glucose-induced endothelial dysfunction in cultured human umbilical vein endothelial cells via PI3K/Akt pathway.

Ibrolipim?5 and 50 μmol/L significantly increased cholesterol efflux from THP-1 macrophage-derived foam cells to apoA-I or HDL. Moreover, it upregulated the expression of ABCA1 and ABCG1. In addition, LXRα was also upregulated by the?ibrolipim?treatment. In addition, LXRα small interfering RNA completely abolished the promotion effect that was induced by?ibrolipim[1].

Ibrolipim (NO-1886; 100 mg/kg; oral administration; daily; for 8 weeks; female Sprague-Dawley rats) treatment decreases accumulation of visceral fat and suppresses the increase in body weight resulting from the ovariectomy. Ibrolipim decreases the respiratory quotient and increases expression of the fatty acid translocase messenger RNA (mRNA) in the liver, soleus muscle, and mesenteric fat. Ibrolipim also increases the expression of fatty acid-binding protein mRNA in the liver and soleus muscle and the expression of the uncoupling protein 3 (UCP3) mRNA in the heart, soleus muscle, and mesenteric fat, but not in the brown adipose tissue[2]

Human THP-1 cells pre-incubated with ox-LDL served as foam cell models. Specific mRNA was quantified using real-time RT-PCR and protein expression using Western blotting. Cellular cholesterol handling was studied using cholesterol efflux experiments and high performance liquid chromatography assays[1]

Animal Model: Female Sprague-Dawley rats (10-week-old; 200-260 g) with experimental ovariectomy treatment. Dosage: 100 mg/kg ? ? ??. Administration: Oral administration; daily; for 8 weeks[2]