Effect of SMP-500, a Novel Acyl-CoA:Cholesterol Acyltransferase Inhibitor, on Serum Cholesterol Level and LDL Cholesterol Clearance in Hamsters with Induced Hyperlipidemia

Ioriya, Katsuhisa; Kino, Katsuhito; Sato, Yumi F; Ohashi, Naohito

doi:10.1159/000065633

Cited by 3 publications

(3 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For some ACAT inhibitors, adverse effects such as diarrhea and cytotoxicity to normal tissues still remain problematic in hyperlipidemia therapy. Recently, many natural or synthetic compounds have been reported as potent ACAT inhibitors with little toxicity (Ioriya et al , ; Adameova et al , ; Ban et al , ; Ohshiro et al , ).…”

Section: Introductionmentioning

confidence: 99%

Essential Oil of Pinus koraiensis Leaves Exerts Antihyperlipidemic Effects via Up‐regulation of Low‐density Lipoprotein Receptor and Inhibition of Acyl‐coenzyme A: Cholesterol Acyltransferase

Kim

Lee

Jeong

et al. 2012

Phytotherapy Research

View full text Add to dashboard Cite

Hyperlipidemia is an important factor to induce metabolic syndrome such as obesity, diabetes and cardiovascular diseases. Recently, some antihyperlipidemic agents from herbal medicines have been in the spotlight in the medical science field. Thus, the present study evaluated the antihyperlipidemic activities of the essential oil from the leaves of Pinus koraiensis SIEB (EOPK) that has been used as a folk remedy for heart disease. The reverse transcription polymerase chain reaction (RT-PCR) revealed that EOPK up-regulated low density lipoprotein receptor (LDLR) at the mRNA level as well as negatively suppressed the expression of sterol regulatory element-binding protein (SREBP)-1c, SREBP-2, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), fatty acid synthase (FAS) and glycerol-3-phosphate acyltransferase (GPAT) involved in lipid metabolism in HepG2 cells. Also, western blotting showed that EOPK activated LDLR and attenuated the expression of FAS at the protein level in the cells. Consistently, EOPK significantly inhibited the level of human acylcoenzyme A: cholesterol acyltransferase (hACAT)1 and 2 and reduced the low-density lipoprotein (LDL) oxidation activity. Furthermore, chromatography-mass spectrometry (GC-MS) analysis showed that EOPK, an essential oil mixture, contained camphene (21.11%), d-limonene (21.01%), α-pinene (16.74%) and borneol (11.52%). Overall, the findings suggest that EOPK can be a potent pharmaceutical agent for the prevention and treatment of hyperlipidemia.

show abstract

Section: Introductionmentioning

confidence: 99%

Essential Oil of Pinus koraiensis Leaves Exerts Antihyperlipidemic Effects via Up‐regulation of Low‐density Lipoprotein Receptor and Inhibition of Acyl‐coenzyme A: Cholesterol Acyltransferase

Kim

Lee

Jeong

et al. 2012

Phytotherapy Research

View full text Add to dashboard Cite

show abstract

“…In addition, studies also reported a significant development of the disease for other hamster strain, with a range of cholesterol from 0.1-1.0% and the period of dietary intervention as early as two weeks up to 40 weeks (Ahmed 2009;Chen et al 2014;Cherng & Shih 2005;Huang et al 2015;Ioriya et al 2002;Jayachandran et al 2015Jayachandran et al , 2015Kanashiro et al 2007;Krause et al 1992;Lin et al 2013;Lin et al 2012;Mawatari et al 2004;Romain et al 2014;Romain et al 2012;Singh et al 2013;Singh et al 2015;Uehara et al 2002;Vide et al 2015;Zha et al 2009).…”

Section: The Role Of High Fat High Cholesterol (Hfhc) Diet In the Devmentioning

confidence: 98%

“…Hamster is reported to develop the hyperlipidemic condition as early as seven days (Singh et al 2013) to two weeks of feeding (Ioriya et al 2002;Takenaga et al 2000) with HFHC diet. Additionally, researchers have also reported the ability of this model to develop the fatty streak in the aorta as early as 10 weeks (Asami et al 1999;Huang et al 2015;Vinson et al 2001;Vinson et al 2002) to 12 weeks (Auger et al 2005;Kowala et al 1995a;Vide et al 2015) of feeding with HFHC diet.…”

Section: The Golden-syrian Hamster As Hyperlipidemia and Atheroscleromentioning

confidence: 99%

Coconut Oil and Cholesterol as Challenge Agents to Induce Hyperlipidemia and Atherosclerosis in Hamster Animal Model

Naina-Mohamed¹

2018

View full text Add to dashboard Cite

ABSTRAKHiperlipiedmia adalah keadaan paras lipid tinggi dalam plasma dan sering dikaitkan dengan pemendapan titisan lipid dalam aorta yang menyebabkan kejadian aterosklerosis. Aterosklerosis adalah penyakit kardiovaskular yang bermula dengan pembentukan sel-sel busa di dalam dinding vascular, seterusnya menyebabkan aliran darah bergelora, kecederaan pada lapisan endotelial dan trombosis pada pembuluh darah. Sejak awal 1980-an, hamster Golden-Syrian telah digunakan secara meluas sebagai model haiwan dalam penyelidikan hiperlipiedmia dan aterosklerosis. Penggunaan hamster sebagai model hiperlipiedmia dan aterosklerosis adalah kerana profil lipoprotein mereka yang lebih dekat dengan penetapan manusia, sensitif terhadap diet tinggi-lemak tinggi-kolesterol (TLTK) dan model roden yang sesuai. Aterosklerosis boleh dicetus ke atas hamster melalui cabaran diet TLTK. Selama beberapa dekad, minyak kelapa (MK) biasa digunakan sebagai sumber lemak dalam reka bentuk diet berkomposisi asid lemak tepu tinggi (ALT). Dalam ulasan ini, kami merumuskan literatur yang diterbitkan dengan reka bentuk yang melibatkan MK-dan kolesterol-cetusan hiperlipidmia, aterosklerosis atau kedua-duanya. Faktor-faktor yang mungkin mempengaruhi kebolehan campuran MK dan kolesterol untuk menggalakkan hiperlipiedmia seperti tempoh diet, jenis hamster dan jumlah pemakanan akan dinilai dan diringkaskan. ABSTRACTHyperlipidemia is a condition of high lipid levels in the plasma and often linked with the deposition of lipid droplets in the aorta which initiate the progression of atherosclerosis. Atherosclerosis is a common cardiovascular disorder initiated by the formation of foams cells in the vascular wall which leads to turbulent blood flow, injury to the endothelial layer and subsequent vascular thrombosis. Since the early 1980's, Golden-Syrian hamsters have been widely used as an animal model in the research of hyperlipidemia and atherosclerosis. The use of hamsters in the hyperlipidemic and atherosclerotic model is due to their lipoprotein profile that is closer to human setting, sensitive to high-fat high-cholesterol (HFHC) diet and a suitable rodent model. Atherosclerosis can be induced in hamsters through dietary challenge with HFHC diet. Over the decades, coconut oil (CNO) was commonly used as the source of fat in the diet design of high saturated fatty acids (SFA) composition. In this review, we summarized published literature with designs involving CNO plus cholesterol-induced hyperlipidemia, atherosclerosis or both. The factors that may influence the ability of CNO and cholesterol combination to induce hyperlipidemia such as the period of dietary intervention, hamster strains and the dietary amount were evaluated and summarized.

show abstract

Pharmacological Profile of SMP-797, a Novel Acyl-Coenzyme A: Cholesterol Acyltransferase Inhibitor with Inducible Effect on the Expression of Low-Density Lipoprotein Receptor

Ioriya

Kino²,

Horisawa³

et al. 2006

Journal of Cardiovascular Pharmacology

View full text Add to dashboard Cite

We investigated the pharmacological profile of SMP-797, a novel hypocholesterolemic agent. SMP-797 showed inhibitory effects on acyl-coenzyme A: cholesterol acyltransferase (ACAT) activities in various microsomes and in human cell lines, and hypocholesterolemic effects in rabbits fed a cholesterol-rich diet and hamsters fed a normal diet. In hamsters, the reduction of total cholesterol level by SMP-797 was mainly due to the decrease of low-density lipoprotein (LDL) cholesterol level rather than that of very low-density lipoprotein (VLDL) cholesterol level. Interestingly, SMP-797 increased the hepatic low-density lipoprotein receptor expression in vivo when it decreased the low-density lipoprotein cholesterol level. SMP-797 also increased low-density lipoprotein receptor expression in HepG2 cells like atorvastatin, an HMG-CoA reductase inhibitor, although other acyl-coenzyme A: cholesterol acyltransferase inhibitor had no effect. In addition, SMP-797 had no effect on cholesterol synthesis in HepG2 cells. These results suggested that the increase of low-density lipoprotein receptor expression by SMP-797 was independent of its acyl-coenzyme A: cholesterol acyltransferase inhibitory action and did not result from the inhibition of hepatic cholesterol synthesis. In conclusion, these results suggest that SMP-797 is a novel hypocholesterolemic agent showing a cholesterol-lowering effect in which the increase of hepatic low-density lipoprotein receptor expression as well as the inhibition of acyl-coenzyme A: cholesterol acyltransferase is involved.

show abstract

Effect of SMP-500, a Novel Acyl-CoA:Cholesterol Acyltransferase Inhibitor, on Serum Cholesterol Level and LDL Cholesterol Clearance in Hamsters with Induced Hyperlipidemia

Cited by 3 publications

References 39 publications

Essential Oil of Pinus koraiensis Leaves Exerts Antihyperlipidemic Effects via Up‐regulation of Low‐density Lipoprotein Receptor and Inhibition of Acyl‐coenzyme A: Cholesterol Acyltransferase

Essential Oil of Pinus koraiensis Leaves Exerts Antihyperlipidemic Effects via Up‐regulation of Low‐density Lipoprotein Receptor and Inhibition of Acyl‐coenzyme A: Cholesterol Acyltransferase

Coconut Oil and Cholesterol as Challenge Agents to Induce Hyperlipidemia and Atherosclerosis in Hamster Animal Model

Pharmacological Profile of SMP-797, a Novel Acyl-Coenzyme A: Cholesterol Acyltransferase Inhibitor with Inducible Effect on the Expression of Low-Density Lipoprotein Receptor

Contact Info

Product

Resources

About