Atrovenetin

Rho GTPases orchestrate signaling pathways leading to cell migration. Their function depends on GTP loading and isoprenylation by geranylgeranyl pyrophosphate (GGpp). In this study, we show that in human T cells, geranylgeranylation-and not GTP loading-is necessary for RhoA-mediated downstream events. As a result of GGpp depletion with the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin, RhoA was sequestered from the membrane to the cytosol and, notwithstanding increased GTP loading, the constitutive activation of its substrate Rho-associated coiled-coil protein kinase-1 was blocked. In line with this, T cells expressing increased GTP-RhoA failed to form an intact cytoskeleton and to migrate toward a chemokine gradient. In vivo treatment with atorvastatin in the rodent model of multiple sclerosis markedly decreased the capacity of activated T cells to traffic within the brain, as demonstrated by multiphoton analysis. Thus, tethering of RhoA to the membrane by GGpp is determinant for T cell migration and provides a mechanism for preventing T cell infiltration into inflamed compartments by 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors.

The present study was undertaken to explore the antihyperlipidemic effect of ethanolic extract of seeds of Apium graveolens L. and its chloroform and aqueous basic fraction in olive oil induced hyperlipidemic rats. The antihyperlipidemic activity of Apium graveolens was compared with a standard drug Atrovastatin (50mg/kg). The study involved phytochemical screening and chromatographic studies of extract and fractions. The ethanolic extract and its fractions were administered orally at doses of 200 and 400 mg/kg body weight in rats. Olive oil (5ml/kg oral dose) was administered 30 min after treatment. Blood was collected by ocular puncture 2 and 4 h after olive oil treatment and centrifuged at 3000 rpm for 15-20 min. Serum samples were further subjected to biochemical analysis. The study dose dependently inhibited the total cholesterol (TC) triglycerides (TG), low density lipoproteins (LDL) level, and significantly increased high density lipoprotein (HDL) level. Phytochemical screening revealed the presence of terpenoid, tannin, alkaloid, glycoside, flavanoid and sterols. UV λmax was found to be 206 nm with a melting point of 137-138°C for the isolated component. The antihyperlipidemic effect was evaluated in olive oil loaded rats. Acute treatment caused stimulatory effect on HDL level and inhibition in TC and TG elevation induced by olive oil.

We identified 155 patients who were admitted with an acute coronary syndrome and a low-density lipoprotein cholesterol level