• Archives of Pharmacal Research
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• v.27 no.6
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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.

• Proceedings of the PSK Conference
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• 2003.10b
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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)

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.202.2-202.2
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• 2002

• Journal of Microbiology and Biotechnology
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• v.12 no.2
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.2
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• pp.293-297
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• 2016

Hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) is the rate-limiting enzyme in biosynthesis of cholesterol in animals. In this study, inhibitory effects of isoflavone glycosides on HMG-CoA reductase were investigated. At sample concentration of $100{\mu}M$, genistein-7-O-triglucoside (G2-genistin) inhibited HMG-CoA reductase activity by approximately 18%, whereas daidzein-7-O-triglucoside had no inhibitory effect. In the kinetic experiments with Syrian hamster HMG-CoA reductase, G2-genistin showed inhibitory efficacy with an invariable $V_{max}$ value, suggesting that G2-genistin works as a competitive inhibitor of HMG-CoA reductase and has potential for hypocholesterolemic action through direct regulation of HMG-CoA reductase.

• KSBB Journal
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• v.6 no.1
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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.

• Korean Journal of Food Science and Technology
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• v.35 no.2
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• pp.297-301
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• 2003

An inhibitor of squalene synthase, a key enzyme in the cholesterol biosynthetic pathways and a target for improved agents to lower plasma levels of low-density lipoprotein, was sequentially purified from Curcuma longa by acetone extraction, silica gel column chromatography, and sephadex LH-20 column chromatography. Active compound, YUF-01, was successfully purified and analyzed as $C_{20}H_{21}O_6$ by electron ionization mass spectrum. Through $^1H-NMR$ and $^{13}C-NMR$ analyses, YUF-01 was identified as curcumin, which showed strong inhibition of squalene synthase.

• Journal of Microbiology and Biotechnology
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• v.29 no.10
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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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• 2002.04a
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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.