Characterization of a novel β-hydroxy-β-methyl glutaryl coenzyme A reductase-inhibitor from the mushroom,Pholiota adiposa

This study describes the extraction and characterization of a novel inhibitor against β-hydroxy-β-methyl glutaryl (HMG) Coenzyme A (CoA) reductase from the mushroomPholiota adiposa. Methanol extracts ofP. adiposa PAD-022 fruiting body showed the highest HMG-CoA reductase-inhibitory activity of 55.8%. The HMG-CoA reductase-inhibitor,P. adipos a PAD-022, was maximally extracted when its fruiting body was treated with methanol at 30°C for 12 h. The HMG-CoA reductase-inhibitor was obtained by systematic solvent extraction methods followed by gel column chromatography, and RP-HPLC. The purified product was found to possess an activity of IC50 6.8 μg and a yield of 1.8%. The molecular weight of purified HMG-CoA reductase-inhibitor was deduced to be 412.7 Da. The inhibitor was identified as stigmasterol (C29H46O) by serial instrumental analyses, including LC-Mass. NMR, FT-IR, and UV spectrometry.

[1]  J. Tobert New developments in lipid-lowering therapy: the role of inhibitors of hydroxymethylglutaryl-coenzyme A reductase. , 1987, Circulation.

[2]  J. Porter,et al.  3-hydroxy-3-methylglutaryl-CoA reductase from rat liver. , 1981, Methods in enzymology.

[3]  S. Moon,et al.  Daio-Orengedokuto inhibits HMG-CoA reductase and pancreatic lipase. , 2002, Biological & pharmaceutical bulletin.

[4]  V. Rodwell,et al.  Investigation of the conserved lysines of Syrian hamster 3-hydroxy-3-methylglutaryl coenzyme A reductase. , 1999, Biochemistry.

[5]  Jae-Ho Kim,et al.  Screening of Mushrooms Having Angiotensin I-Converting Enzyme Inhibitor , 2003 .

[6]  Baojun Xu,et al.  Enhanced lovastatin production by solid state fermentation ofMonascus ruber , 2005 .

[7]  V. Rodwell,et al.  Catalysis by Syrian hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Proposed roles of histidine 865, glutamate 558, and aspartate 766. , 1994, The Journal of biological chemistry.

[8]  S. Choi,et al.  Isoflavones Found in Korean Soybean Paste as 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Inhibitors , 2004, Bioscience, biotechnology, and biochemistry.

[9]  Michael A. Wilson,et al.  Hypoglycemic Effect of Exo- and Endo-biopolymers Produced by Submerged Mycelial Culture of Ganoderma lucidum in Streptozotocin-Induced Diabetic Rats , 2004 .

[10]  M. Johari,et al.  Preservation of coagulation efficiency ofMoringa oleifera, a natural coagulant , 2006 .

[11]  D. Hunninghake,et al.  Effects of fluvastatin (XU 62-320), an HMG-CoA reductase inhibitor, on the distribution and composition of low density lipoprotein subspecies in humans. , 1991, Atherosclerosis.

[12]  Y. Tsujita,et al.  ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinium. , 1976, The Journal of antibiotics.

[13]  H. Chun,et al.  Effect of a Pholiota adiposa Extract on Fat Mass in Hyperlipidemic Mice , 2006, Mycobiology.

[14]  Myoung-Dong Kim,et al.  Expression and purification of ubiquitin-specific protease (UBP1) ofSaccharomyces cerevisiae in recombinantEscherichia coli , 2005 .

[15]  Soo-Muk Cho,et al.  Detection of Platelet Aggregation Inhibitors and Fibrinolytic Substances from Mushrooms , 2003 .

[16]  J. Deisenhofer,et al.  Structural Mechanism for Statin Inhibition of HMG-CoA Reductase , 2001, Science.

[17]  D. Choi,et al.  Effects ofFomitopsis pinicola extracts on antioxidant and antitumor activities , 2007 .

[18]  Y. Chang,et al.  Optimization of submerged culture conditions for mycelial growth and exopolysaccharides production by Agaricus blazei , 2004 .

[19]  K. Ra,et al.  Immunomodulating Activity of the Exopolymer from Submerged Mycelial Culture of Phellinus pini , 2004 .

[20]  W. Bartmann,et al.  Synthesis and biological activity of new HMG-CoA reductase inhibitors. 1. Lactones of pyridine- and pyrimidine-substituted 3,5-dihydroxy-6-heptenoic (-heptanoic) acids. , 1990, Journal of medicinal chemistry.

[21]  K. Hasumi,et al.  Dihydromonacolin L and monacolin X, new metabolites which inhibit cholesterol biosynthesis. , 1985, The Journal of antibiotics.

[22]  Young Soon Kim,et al.  Optimization of the sucrose and ion concentrations for saikosaponin production in hairy root culture ofBupleurum falcatum , 2006 .

[23]  M. M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[24]  K. Kang,et al.  Inhibition of telomerase activity in U937 human monocytic leukemia cells by Compound K, a ginseng saponin metabolite , 2006 .

[25]  Keyong-Ho Lee,et al.  Antitumor activity of cell suspension culture of green tea seed (Camellia sinensis L.) , 2006 .

[26]  Y. Chang,et al.  On-line estimation of cell growth from agitation speed in DO-stat culture of a filamentous microorganism,Agaricus blazei , 2005 .

[27]  Jae-Ho Kim,et al.  Production and characterization of antihypertensive angiotensin I-converting enzyme inhibitor from Pholiota adiposa , 2006 .

[28]  Jongsoo Lee,et al.  Characterization of β-Hydroxy-β-methylglutaryl Coenzyme A Reductase Inhibitor from Pueraria thunbergiana , 2005 .

[29]  M D Siperstein,et al.  Feedback control of mevalonate synthesis by dietary cholesterol. , 1966, The Journal of biological chemistry.

[30]  W. Bartmann,et al.  Stereoselective synthesis of HR 780 a new highly potent HMG-CoA reductase inhibitor , 1990 .

[31]  Marvin D. Siperstein,et al.  Regulation of cholesterol biosynthesis in normal and malignant tissues. , 1970 .