• Korean Journal of Food Science and Technology
• /
• v.35 no.2
• /
• pp.297-301
• /
• 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
• /
• v.17 no.12
• /
• pp.1970-1975
• /
• 2007

Squalene synthase plays an important role in the cholesterol biosynthetic pathway. Inhibiting this enzyme in hypercholesterolemia can lower not only plasma cholesterol but also plasma triglyceride levels. A squalene synthase inhibitor was screened from Prunus mume fruit, and then purified via sequential processes of ethanol extraction, HP-20 column chromatography, ethyl acetate extraction, silica gel column chromatography, and crystallization. The squalene synthase inhibitor was identified as chlorogenic acid with a molecular mass of 354 Da and a molecular formula of $C_{16}H_{18}O_9$ based on UV spectrophotometry, $^1H$ and $^{13}C$ NMRs, and mass spectrometry. Chlorogenic acid inhibited the squalene synthase of pig liver with an $IC_{50}$ level of 100 nM. Since chlorogenic acid was an effective inhibitor against the squalene synthase of an animal source, it may be a potential therapeutic agent for hypercholesterolemia.

• Journal of Microbiology and Biotechnology
• /
• v.12 no.2
• /
• pp.222-227
• /
• 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.

• Food Science and Biotechnology
• /
• v.14 no.1
• /
• pp.89-93
• /
• 2005

Squalene synthase (SQS) inhibitors were screened from various plants and food extracts. Effective SQS inhibitor was purified from fermented soybean paste using ethanol extraction, HP-20 column chromatography, ethyl acetate extraction, silica gel column chromatography, and crystallization. Through UV spectrometry, $^1H$ NMR, $^{13}C$ NMR, and mass spectrometry, SQS inhibitor was identified as daidzein with molecular mass of 254 and molecular formula of $C_{15}H_{10}O_4$. Daidzein showed $IC_{50}$ value of 50 nmol/L against SQS, confirming its potential as therapeutic agent for hypercholesterolemia.

• Journal of Life Science
• /
• v.18 no.2
• /
• pp.273-278
• /
• 2008

Various biological resources from plants, animals, mushrooms, microorganisms, and foods were tested for the inhibitory activity against squalene synthase (SQS). Among 32 samples, more than one fourths (9 samples) exhibited significant SQS inhibitory activity. Interestingly, SQS inhibitory activity was detected in the samples such as green tea, fermented soybean paste, and plum juice. The SQS inhibitory activity of green tea was not only high but also stable. Its SQS inhibitors were supposed to be catechin derivatives, which have been known to be main bioactive components in green tea. The galloyl catechins showed higher SQS inhibitory activity compared to the nongalloyl catechins. Especially, (-)-epigallocatechin gallate appeared to be strongest inhibitor against squalene synthase ($IC_{50}=90{\mu}M$).