title: The novel inhibitory effect of Pangdahai on fatty acid synthase.
abstract: 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.
authors: School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing, China.
authors: Wen-Hua
authors: WH
authors: Zhao
authors: Chun-Yang
authors: CY
authors: Zhao
authors: Li-Fang
authors: LF
authors: Gao
authors: Fei-Fei
authors: FF
authors: Feng
authors: Wen
authors: W
authors: Gao
authors: Zhen-Liang
authors: ZL
authors: Chen
authors: Feng
authors: F
authors: Zhang
authors: Li-Ge
authors: LG
authors: Cao
authors: Xiao-Yu
authors: XY
authors: Bi
authors: Yue
authors: Y
authors: Chen
authors: Qi-Yao
authors: QY
authors: Zhu
authors: Ying-Xia
authors: YX
authors: Zhang
mesh_terms: D000818:Animals; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000431:Ethanol / Q000737:chemistry; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008516:Medicine, Chinese Traditional; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D009765:Obesity / Q000188:drug therapy; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D032361:Sterculia / Q000737:chemistry; D015431:Weight Loss
chemical_list: D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D010936:Plant Extracts; D000431:Ethanol; D064429:Fatty Acid Synthases; C528992:pangdahai