The novel inhibitory effect of Pangdahai on fatty acid synthase.
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.
Zhao
Wen-Hua
WH
School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing, China.
Zhao
Chun-Yang
CY
Gao
Li-Fang
LF
Feng
Fei-Fei
FF
Gao
Wen
W
Chen
Zhen-Liang
ZL
Zhang
Feng
F
Cao
Li-Ge
LG
Bi
Xiao-Yu
XY
Chen
Yue
Y
Zhu
Qi-Yao
QY
Zhang
Ying-Xia
YX
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
D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D010936:Plant Extracts; D000431:Ethanol; D064429:Fatty Acid Synthases; C528992:pangdahai