• Archives of Pharmacal Research
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• 제27권6호
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• pp.624-627
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• 2004

A bile acid derivative, methyl chalate （1）, was isolated from EtOAc extract of the fungus Rhizopus oryzae as a cholesterol biosynthesis inhibitor. It showed moderate inhibitory activity on cholesterol biosynthesis in human Chang liver cells. Compound 1 exhibited inhibitory effect on the later step of cholesterol biosynthesis, indicating that its action mode is different from that of statins that act on the HMG-CoA reductase.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.184.2-184.2
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• 2003

Many naturally occurring polyhydroxylated sterols and oxysterols exhibit potent biologic activities. The role of oxycholesterol including 2, 5(R)-2, 6-hydroxycholesterol is a potent inhibitor of cholesterol biosynthesis in vitro as it is an effective inhibitor of HMG-Coa reductase. Some new polyhydroxylated sterols were showed potent cytotoxicity to cancer cells. And it has also been chown to be an inhibitor of DNA synthesis, In order to synthesize the various oxy derivatives, we tried to positionselective and reagentselective epoxidation and reduction of cholesterol derivatives. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.202.2-202.2
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• 2002

• Journal of Microbiology and Biotechnology
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• 제12권2호
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• pp.222-227
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• 2002

Squalene synthase catalyzes the reductive dimerization of two molecules of farnesyl diphosphate to form squalene at the final branch point of the cholesterol biosynthetic pathway. Due to the unique position of this enzyme in the pathway, its inhibitors may have advantages as antihypercholesterolemic agents. Therefore, selective inhibitors of squalene synthase do not prevent the formation of the essential branch products of the isoprene pathway, such as dolichol, coenzyme-Q, and prenylated proteins, as might be expected for inhibitors of enzymes earlier in the pathway; for example, lovastatin and mevalotin. The current study reports that CJ90002, a pentagalloylglucose isolated from Paeonia moutan SIM (Paeoniaceae), which is an important Chinese crude drug used in many traditional prescriptions, was a potent inhibitor of rat microsomal squalene synthase, and also a potent inhibitor of cholesterol biosynthesis in vitro. In addition, the intraperitoneal and oral administration of CJ90002 had a significant lowering effect on plasma cholesterol levels in hamsters.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.5-7
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• 2003

NADPH is an essential co-factor for fat and cholesterol biosynthesis. However, the role of cytosolic NADP$\^$＋/-dependent isocitrate dehydrogenase (IDPc), a putative NADPH producer, in the control of the fat and cholesterol metabolism has not been assessed. Here we report that increased or decreased IDPc expression in 3T3-Ll fat cells promoted or retarded adipogenesis, respectively. Furthermore, overexpression of IDPc in transgenic mice exhibited fatty liver, hypertriglyceridemia, hypercholesterolemia and obesity by increasing NADPH production leading to subsequent stimulation of acetyl-coenzyme A and malonyl-coenzyme A consumption. In contrast, administrations of a synthetic IDPc inhibitor, DAl1004, to ob/ob mice effectively reduced body weight with lowering cholesterol and triglyceride levels. In addition, a positive relationship (${\gamma}$ = 0.69, $\rho$<0.0l) between plasma IDPc activity and body mass indexes was observed in 98 randomly-selected human volunteers. Our findings strongly indicate that NADPH produced by IDPc plays an important role in controlling body fat and lipid biosynthesis.

• 한국식품영양과학회지
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• 제45권2호
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• pp.293-297
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• 2016

HMG-CoA reductase는 체내 콜레스테롤 생합성에 있어서 속도제한단계(율속) 효소이다. 본 연구는 HMG-CoA reductase에 대한 이소플라본 배당체의 저해 효과를 연구하였다. $100{\mu}M$의 농도에서 genistein-7-O-triglucoside(G2-genistin)는 HMG-CoA reductase 활성을 약 18% 정도 저해하였으나, daidzein-7-O-triglucoside는 저해 효과를 갖지 않았다. 시리아햄스터 HMG-CoA reductase의 반응속도 실험에서 G2-genistin은 농도에 관계없이 $V_{max}$의 저해 정도가 일정하였으며, 이것은 G2-genistin이 HMG-CoA reductase의 경쟁적 저해제로 작용함을 시사하고 HMG-CoA reductase의 활성을 직접적으로 저해함으로써 혈중 콜레스테롤 함량을 감소시킬 수 있음을 예상할 수 있다.

• KSBB Journal
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• 제6권1호
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• pp.55-61
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• 1991

The objective of this in vitro study is to screen a possible inhibitor, originated from some chinese herb medicines, of 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase that is the major regulatory enzyme of hepatic cholesterol biosynthesis. Fourteen kinds of herbal plant were extracted with water and evaporated for prescreening. The methanol extracts of the effective 3 kinds (9 species) were fractionated with chloroform, ethylacetate, butanol and water, and vacuum evaporated. The degree of inhibition of the extracts to HMG-CoA reductase activity was calculated by the spectrophotometric method using microsomal protein of Saccharomyces cerevisiae ATCC 42949 as an enzyme source. Among these samples, marked inhibitory effects were observed in the extracts of ethylacetate and chloroform fractions of the Rosa rugosa roots, and those of butanol, ehtylacetate and water fractions of pine leaves. Also, the inhibitory effects of the extracts obtained from buckwheat shell and the roots of Rosaceae were found.

• 한국식품과학회지
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• 제35권2호
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• pp.297-301
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• 2003

동맥경화증과 같은 심혈관 질환을 야기시키는 주요 위험요인인 혈중 콜레스테롤의 수준을 낮추기 위하여 콜레스테롤 생합성 과정의 속도조절단계 효소의 하나인 squalene synthase의 활성을 저해하는 물질을 분리 정제하여, 물질의 이화학적 특성과 생물학적 특성을 검토하였다. Squalene synthase 저해물질은 acetone extraction, ethyl acetate extraction, silica gel column chromatography, sephadex LH-20 column chromatography, 결정화 등을 이용하여 분리 정제하여 YUF-01을 얻었다. 기기분석을 통하여 구조분석을 행한 결과 YUF-01은 분자량 368, 분자식 $C_{20}H_{21}O_6$으로 분석되었으며 243과 421 nm 에서 UV-VIS 흡광을 나타내었고 $^{13}C$ NMR spectrum과 $^1H$ NMR spectrum을 검토하였을 때 aromatic ketone 구조인 curcuminoid 계통의 curcumin과 일치하였다. Squalene synthase에 대한 curcumin의 $IC_{50}$ 값은 $100{\mu}M$이었으며, non-competitive inhibitor로 작용하였다.

• Journal of Microbiology and Biotechnology
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• 제29권10호
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• pp.1570-1579
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• 2019

The fungal products dibenzodioxocinones promise a novel class of inhibitors against cholesterol ester transfer protein (CEPT). Knowledge as to their biosynthesis is scarce. In this report, we characterized four more dibenzodioxocinones, which along with a previously described member pestalotiollide B, delimit the dominant spectrum of secondary metabolites in P. microspora. Through mRNA-seq profiling in $g{\alpha}1{\Delta}$, a process that halts the production of the dibenzodioxocinones, a gene cluster harboring 21 genes including a polyketide synthase, designated as pks8, was defined. Disruption of genes in the cluster led to loss of the compounds, concluding the anticipated role in the biosynthesis of the chemicals. The biosynthetic route to dibenzodioxocinones was temporarily speculated. This study reveals the genetic basis underlying the biosynthesis of dibenzodioxocinone in fungi, and may facilitate the practice for yield improvement in the drug development arena.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2002년도 생물공학의 동향 (X)
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• pp.184-187
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• 2002

Lovastatin is a cholesterol-lowering agent, which plays a role of an inhibitor of 3-hydroxy-3- methylglutaryl coenzyme A reductase (HMG-CoA). When thiamine was supplemented in 3L batch fermentation, the production of lovastatin was improved. At the same time, the levels of pyruvic acid and NAD(P)H were estimated in the course of the fermentation of A. terreus. For the high level production of lovastatin, semi fed-batch fermentation was performed. And the thiamine level was maintained to a concentration of 20 mg/L and glucose was supplied. The final dry cell weight was lowered by 30 % and final lovastatin concentration was increased by 33 %. Final lovastatin concentration of 3.3 g/L was achieved in 8 days.