ABSTRACT
In order to study the anti-obesity ability and inhibition towards fatty acid synthase (FAS) of the extract, a 70% ethanol extract of Acer truncatum Bunge (AT) leaves was further extracted with ethyl acetate. FAS is a very significant lipogenic enzyme, participating in energy metabolism in vivo; it has also been observed that FAS inhibitors might be potent anti-obesity agents. Experimental results on animals showed that the extract significantly reduced food intake and adipose, and effectively controlled weight evolution. Lipogenesis inhibition might be regarded as one of the reasons for the weight control and adipose reduction by AT. The extract was further isolated using a series of column chromatography that yielded 10 known compounds. 1,2,3,4,6-Penta-O-galloyl-ß-D-glucose was found to be one of the major active constituents in the extract of AT.
Subject(s)
Acer/chemistry , Anti-Obesity Agents/therapeutic use , Fatty Acid Synthases/antagonists & inhibitors , Plant Leaves/chemistry , Animals , Anti-Obesity Agents/chemistry , Body Weight/drug effects , Male , Rats , Rats, WistarABSTRACT
Recently, animal fatty acid synthase (FASN) is reported as a potential therapeutic target for obesity and cancer. Considerable interest has been developed in searching for novel inhibitors of this enzyme. An extract from Pangdahai has been found to inhibit FASN in both reversible and irreversible manners, with an IC(50) of 3.5 microg/ml and an apparent inactivation rate constant of k(obs) of 2.2 x 10(-3)/min. The kinetic study showed that the Pangdahai extract inhibited the overall FASN reaction uncompetitively with acetyl-CoA, but it presented in a mixed manner both with NADPH and with malonyl-CoA. Its major reacting site on this enzyme, as compared between two IC(50) values, is not in the beta-ketoacyl reduction domain. A weight reducing experiment in rats showed that the extract significantly reduced the adipose and food intake, but in view of statistics (P < 0.05), a correlation between the reductions in the adipose and in the food consumption and the inhibition of hepatic FASN could not be established. Three known flavonoid compounds were isolated from the extract and the structure-activity relationship was discussed.