Mi Yeon Chung

Inhibitory activity of diacylglycerol acyltransferase by tanshinones from the root of Salvia miltiorrhiza.

The inhibitory activity of tanshinones fromSalvia miltiorrhiza was tested on rat liver diacylglycerol acyltransferase (DGAT). Cryptotanshinone (1) and 15, 16-dihydrotanshinone I (3) exhibited potent DGAT inhibitory activities dose-dependently with IC50 values of 10.5 μg/ml and 11.1 μg/ml. However, tanshinone HA (2) and tanshinone I (4) showed very weak inhibition (IC50 value: > 250 μg/ml). A dihydrofuran moiety was seemed to be responsible for the stronger inhibitory activity

Manassantin a and b isolated fromSaururus chinensis inhibit TNF-α-induced Cell adhesion molecule expression of human umbilical vein endothelial cells

Leukocyte adhesion to the vascular endothelium is a critical initiating step in inflammation and atherosclerosis. We have herein studied the effect of manassantin A (1) and B (2), dineolignans, on interaction of THP-1 monocytic cells and human umbilical vein endothelial cells (HUVEC) and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in HUVEC. When HUVEC were pretreated with1 and2 followed by stimulation with TNF-α, adhesion of THP-1 cells to HUVEC decreased in dose-dependent manner with IC50 values of 5 ng/mL and 7 ng/mL, respectively, without cytotoxicity. Also,1 and2 inhibited TNF-α-induced up-regulation of ICAM-1, VCAM-1 and E-selectin. The present findings suggest that1 and2 prevent monocyte adhesion to HUVEC through the inhibition of ICAM-1, VCAM-1 and E-selectin expression stimulated by TNF-α, and may imply their usefulness for the prevention of atherosclerosis relevant to endothelial activation.

Diacylglycerol acyltransferase-inhibitory compounds from Erythrina senegalensis

Inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT) is proposed to be a drug target for the treatment of obesity and type 2 diabetes. Bioassay-guided fractionation of the CH2Cl2-soluble extract of the stem bark of Erythrina senegalensis, using an in vitro DGAT enzyme assay, resulted in the isolation of eight known prenylflavonoids, 8-prenylleutone (1), auriculatin (2), erysenegalensein O (3), erysenegalensein D (4), erysenegalensein N (5), derrone (6), alpinumisoflavone (7), and 6,8-diprenylgenistein (8). Compounds 1, 2–4, 6, and 8 inhibited DGAT activity, with IC50 values ranging from 1.1 ± 0.3 to 15.1 ± 1.1 μg/mL. On the basis of the data obtained, we propose isoflavonoids with isoprenyl groups as a novel class of DGAT inhibitors.

Pheophorbide a-methyl ester, acyl-coa: cholesterol acyltransferase inhibitor fromDiospyros kaki

In the course of our search for Acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors from natural sources, a new type of ACAT inhibitor was isolated from a methanol extract ofDiospyros kaki. On the basis of spectral and structural evidence, the compound was identified as pheophorbide A-methyl ester. Pheophorbide A-methyl ester inhibited ACAT activity in a dose dependent manner with an IC50 value of 1.85 μg/mL.