| RRC ID |
41939
|
| 著者 |
Ohishi K, Sawada H, Yoshida Y, Yokoi W, Hatano H, Aiyama R, Watanabe T, Yokokura T.
|
| タイトル |
Inhibitory effects of N-(3,5-dimethoxy-4-n-octyloxycinnamoyl)-N'-(3,4-dimethylphenyl)piperazine (YIC-C8-434), an acyl-CoA:cholesterol O-acyltransferase inhibitor, on cholesterol esterification in the intestine and liver.
|
| ジャーナル |
Biol Pharm Bull
|
| Abstract |
The effects of an acyl-CoA:cholesterol O-acyltransferase (ACAT) inhibitor, N-(3,5-dimethoxy-4-n-octyloxycinnamoyl)-N'-(3,4-dimethylphenyl)piperazine (YIC-C8-434), on cholesterol esterification in the intestine and liver were investigated in vitro and in vivo. YIC-C8-434 inhibited the formation of cholesteryl [(3)H]oleate from [(3)H]oleic acid and cholesterol both in human colon adenocarcinoma Caco2 cells and in human hepatoma HepG2 cells with IC(50) values of 0.38 and 0.49 microM, respectively. However, it did not influence the incorporation of [(3)H]oleic acid into triacylglycerols and phospholipids. Oral administration of YIC-C8-434 at a dose of 8.3 mg/kg/d inhibited [(14)C]cholesterol absorption by 17% (p<0.01) in rats. YIC-C8-434 also significantly reduced the secretion of very low-density lipoprotein (VLDL) cholesterol from the liver into the plasma at an oral dose of 100 mg/kg/d after an intravenous injection of Triton WR-1339. These results suggest that oral administration of YIC-C8-434 reduces intestinal cholesterol absorption and hepatic VLDL cholesterol secretion by direct inhibition of ACAT in the intestinal epithelium and hepatocytes, respectively. However, the inhibitory action of YIC-C8-434 on cholesterol absorption rather than hepatic cholesterol secretion may play a more important role in its hypocholesterolemic activity, because the effective dose for the former was 12-fold lower than that for the latter.
|
| 巻・号 |
26(8)
|
| ページ |
1125-8
|
| 公開日 |
2003-8-1
|
| DOI |
10.1248/bpb.26.1125
|
| PMID |
12913263
|
| MeSH |
Animals
Caco-2 Cells
Cholesterol Esters / antagonists & inhibitors
Cholesterol Esters / metabolism*
Cinnamates / pharmacology*
Dose-Response Relationship, Drug
Humans
Intestinal Mucosa / metabolism
Intestines / drug effects
Intestines / enzymology*
Liver / drug effects
Liver / enzymology*
Male
Piperazines / pharmacology*
Rats
Rats, Sprague-Dawley
Sterol O-Acyltransferase / antagonists & inhibitors*
Sterol O-Acyltransferase / metabolism
|
| IF |
1.863
|
| 引用数 |
5
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
| リソース情報 |
| ヒト・動物細胞 |
CAC0-2(RCB0988)
Hep G2(RCB0459) |
