• Food Science and Biotechnology
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• v.14 no.6
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• pp.772-777
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• 2005

The goal of this study was to screen and characterize the physiological functions of Korean traditional wines (TW) and liquors (TL). Forty-two TW and TL were collected and evaluated for quality and cardiovascular activities. Ethanol content ranged from $9.0%{\sim}41%$, and pH ranged from $3.0{\sim}7.8$, and they also contained 0.01% to 0.67% of total acid. Samples contained a maximum of 2.0% of crude protein and $0.1%{\sim}14.0%$ of reducing sugar. Commercial CM-wine showed the highest antihypertensive angiotensin I-converting enzyme (ACE) inhibitory activity, 85.9%. The greatest fibrinolytic activity and platelet aggregation inhibitory activity were also found in commercial CM-wine (31.8U) and commercial SS2-wine (38.6 %), respectively. Commercial SHBI-liquor showed the highest HMG-CoA reductase inhibitory activity, 78%. The ACE inhibitor from commercial CM-wine was a peptide compound and also showed an antihypertensive effect in spontaneous hypertensive rats at a dosage of 1.5 mg/kg.

• Journal of Life Science
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• v.28 no.4
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• pp.472-477
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• 2018

Pravastatin sodium is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor used in the treatment of hypercholesterolemia by reducing cholesterol biosynthesis. Pharmaceutical excipients of commonly used including water, diluents, stabilizers, disintegrants, lubricants and colorants, and were identified for compatibility. All tests were performed by means of physical mixture of pravastatin and the excipients, which were placed in a press-through-pack (PTP) and incubated under accelerated conditions ($40^{\circ}C$ and 75% relative humidity) for 3 months. The blends of pravastatin with all excipients developed white, off white, and light brown powders, which showed no changes upon visual analysis. Accelerated conditions changed the degradation profile of pravastatin calcium in the HPLC system when mixed with different excipients. Although most excipients can have minor effects on pravastatin stability, the major degradation product from pravastatin was lactone. Low-level interaction (assay and impurity) was induced by all excipients except for microcrystalline cellulose and croscarmellose sodium. These excipients increased lactone impurity in 3 months by as much as 0.22% and 0.18% respectively. The total mixture slightly increased the lactone impurity (by 0.43% in 3 months) of pravastatin. There was no change in the assays of all excipients. These results will be helpful in studying tablet size reductions for convenience of use.

• Journal of Pharmaceutical Investigation
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• v.41 no.4
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• pp.239-247
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• 2011

Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin has good permeability, but it also has low solubility (BCS class II), which reduces its bioavailability. To overcome this problem, a solid dispersion is formed using a spray-dryer with polymeric material carrier to potentially enhance the dissolution rate and extend drug absorption. As carriers for solid dispersion, Gelucire$^{(R)}$44/14 and Gelucire$^{(R)}$ 50/13 are semisolid excipients that greatly improve the bioavailability of poorly-soluble drugs. To avoid any toxic effects of an organic solvent, we used aqueous medium to melt Tween$^{(R)}$ 80 and distilled water. The structural behaviors of the raw materials and the solid dispersion were analyzed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and PXRD data indicated that the crystalline structure of simvastatin was transformed to an amorphous structure through solid dispersion. Then, solid dispersion-based tablets containing 20 mg simvastatin were prepared with excipients. Dissolution tests were performed in distilled water and artificial intestinal fluid using the USP paddle II method. Compared with that of the commercial tablet (Zocor$^{(R)}$ 20 mg), the release of simvastatin from solid dispersion based-tablet was more efficient. Although the stability study is not complete, this solid dispersion system is expected to deliver poorly water-soluble drugs with enhanced bioavailability and less toxicity.

• Korean Journal of Clinical Pharmacy
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• v.23 no.4
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• pp.316-321
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• 2013

Purpose: Atorvastatin, a HMG-CoA reductase inhibitor is widely prescribed in hyperlipidemic patients and telmisartan, an angiotensin receptor blocker is frequently used in the treatment of hypertension. Both drugs are substrates of organic anion transporting polypeptide (OATP) expressed in basolateral membrane in the liver, and undergo high first pass metabolism. Therefore, OATP-mediated hepatic uptake is important for disposition and metabolism of these drugs. The present study was designed to investigate the pharmacokinetic interactions between atorvastatin and telmisartan in rats. Method: Young adult SD rats were divided into three groups (n=6, each) and atorvastatin (10 mg/kg) and telmisartan (4 mg/kg) were orally given alone and together. Heparinized blood was serially taken and plasma concentrations of both drugs were measured using HPLC-MS/MS. Pharmacokinetic parameters of two drugs were calculated. Results: No significant pharmacokinetic change was found except a delay of time to peak of telmisartan when administered with atorvastatin. Each drug at the present dosage seemed to be insufficient to alter the pharmacokinetic parameters of its counterpart drug. Conclusion: Conclusively, co-administration of atorvastatin and telmisartan may lead to negligible clinical consequences.

• Advances in Traditional Medicine
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• v.10 no.4
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• pp.239-253
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• 2010

Coenzyme $Q_{10}$ ($CoQ_{10}$, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of $CoQ_{10}$ in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in $CoQ_{10}$ status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of $CoQ_{10}$ biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of $CoQ_{10}$ status following HMG-CoA reductase inhibitor (statins) treatment has been implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. $CoQ_{10}$ and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Friedreich's ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of $CoQ_{10}$, as well as the rationale and the role in clinical practice of $CoQ_{10}$ supplementation in different neurological diseases, from primary $CoQ_{10}$ deficiency to neurodegenerative disorders. These will help in future for treatment of patients suffering from neurodegenerative disease.

• Journal of Microbiology and Biotechnology
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• v.8 no.3
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• pp.295-299
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• 1998

Oligonucleotide primers were designed and successfully applied to amplify DNA fragments of P450 hydroxylase genes from actinomycetes which produce a large variety of medically important metabolites. Primers were designed based on several regions of strong similarities in amino acid sequence of P450 hydroxylases from a variety of actinomycetes, primarily in the regions of an oxygen binding site and a heme ligand pocket. These primers were used to amplify DNA fragments from seven different actinomycetes species producing a variety of different compounds. The deduced amino acid sequences of the isolated fragments revealed significant similarities to known P450 hydroxylase including the product of the suaC or subC genes from Streptomyces griseolus that is capable of metabolizing a number of sulfonylurea herbicides, and to the product of the $P450_{sca2}$ from S. carbophilus that produces a specific HMG-CoA reductase inhibitor. This method should help researchers in cloning the P450 hydroxylase genes involved in the biosynthesis of useful compounds.

• Journal of Pharmaceutical Investigation
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• v.30 no.4
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• pp.279-282
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• 2000

Simple and precise high-performance liquid chromatographic (HPLC) assay was developed and validated for the determination of a HMG-CoA reductase inhibitor, $lovastatin^{TM}$ and its active metabolite (mevinolinic acid) in human plasma. The method involved solid phase extraction of mevinolinic acid and internal standard using Sep-Pak Cartridge. Samples were analyzed by reversed-phase HPLC using $Capcell-Pak\;C_{18}$ column with ultraviolet detection at 238 nm. The quantitation limit of mevinolinic acid was 2 ng/ml and the calibration curve was linear over the range of 2-50 ng/ml $(r^2>0.999)$ with human plasma. The analyses of quality control samples indicated that the normal values could be predicted with an accuracy >97%. The intra- and inter-day coefficients of variation for the analyses were <10%. The average recoveries were similar (79%) for mevinolinic acid and methylmevinolinic acid. The method described has been successfully applied to the quantification of mevinolinic acid in about 1,000 human plasma samples over six-month period.

• Childhood Kidney Diseases
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• v.7 no.1
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• pp.9-15
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• 2003

Purpose : Several studies have suggested that hyperlipidemia might be a causative factor contributing to the progression of initial glomerular injury through the development of glomerulosclerosis. We examined the potential beneficial effect of atorvastatin - which blocks the rate limiting step of cholesterol synthesis by inhibiting HMG-CoA reductase - in PAN-induced nephrosis. Materials and Methods : Glomerulosclerosis was induced in Sprague-Dawley male rats by repeated administration of PAN. Sprague-Dawley male rats were divided into 3 groups : group I(control), group II(PAN 20 mg/kg, subcutaneous injection), group III(PAN 20 mg/kg subcutaneous injection and atorvastatin 50 mg/kg/day per oral). On the 11th week, upon sacrifice of the experimental animals, blood sampling, 24-hr urine collection and nephrectomy were performed. Results : Group III had significantly lower BUN and higher serum albumin($30.9{\pm}17.2\;vs.\;17.3{\pm}2.5\;mg/dL;\;2.3{\pm}0.1\;vs.\;2.5{\pm}0.2\;g/dL$, P<0.05) compared with group II. In the lipid profiles, group III was associated with a reduction in total cholesterol and LDL($291{\pm}173\;vs.\;167{\pm}72\;mg/dL:\;57{\pm}53\;vs.\;27{\pm}12\;mg/dL$, P>0.05) compared with group II. Atorvastatin administration lowered the glomerular sclerosing index significantly(26.2% vs. 13.3%, P<0.05). Conclusion : Puromycin-induced glomerulosclerosis could be ameliorated by the reduction of hyperlipidemia with atorvastatin. This suggests that hyperlipidemia contributes to the pathogenesis of glomerulosclerosis.

• Food Science and Preservation
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• v.9 no.1
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• pp.28-35
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• 2002

This study was conducted to evaluate the quality characteristics of different soy sauces. The soybean sauces brewed tty the A. oryzae koji(SAO), M. pilosus-1 koji(SMP) and the mixture of 50% M. pilosus-1 koji(SAM) during 90 days fermentation. Total nitrogen contents of the SAM, SAP and SMP were 13.6%, 1.15% and 1.22%, respectively. Content of amino type nitrogen in SAM was 0.78%, and the content was higher than those of SAO and SMP. Total free amino acid contents of SAO, SMP and SAM were 533.8, 732.4 and 807.3 mg/100 mL. The highest contents of free, amino acids were glutamic acid(65.20 mg/100 mL) in SAG, alanine(101.42 mg/100mL) in SMP, glutamic acid(130.52 mg/100 mL) in SAM. The highest activities of pretense and ${\beta}$-amylase showed in SAM, and the lowest activities of ${\alpha}$-amylase and glucoamylase were in SAO and SMP respectively. Hue angle values showed 56.3 in SAO, 29.0 in SMP and 32.2 in SAM. Monacolin K contents, as inhibitor of cholesterol bio-synthesis were 6.21 $\mu\textrm{g}$/mL for SMP and 3.10 $\mu\textrm{g}$/mL for SAM, and the inhibitory activities of SMP ane SAM aginst HMG-CoA reductase were 21.5 md 10.2%, respectively. Sensory scores for color, flavor, savory taste and overall taste of SAM was higher than those of SAO and SMP.

• Journal of Microbiology
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• v.40 no.3
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• pp.211-218
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• 2002

A 4.8-kb DNA fragment encoding the P-450 type hydroxylase and ferredoxin genes was cloned from Pseudonocardia autotrophica IFO 12743 that can convert vitamin D$\_$3/ into its hydroxylated active forms. In order to isolate the P-450 gene cluster in this organism, we designed PCR primers on the basis of the regions of an oxygen binding site and a heme ligand pocket that are general characteristics of the P-450 hydroxylase. Sequencing analysis of the BamHI fragment revealed the presence of four complete and one incomplete ORFs, named PauA, PauB, PauC, and PauD, respectively. As a result of computer-based analyses, PauA and PauB have homology with enoyl-CoA hydratase from several organisms and the positive regulators belonging to the tetR family, respectively. PauC and PauD show similarity with SuaB/C proteins and ferredoxins, respectively, which are composed of P-450 monooxygenase systems for metabolizing two sulfonylurea herbicides in Streptomyces griseolus PauC shows the highest similarity with another CytP-450$\_$Sca2/ protein that is responsible for production of a specific HMG-CoA reductase inhibitor, pravastatin, in S. carbophilus. Cultures of Steptomyces lividans transformant, containing the P-450 gene cluster on the pWHM3 plasmid, was unable to convert vitamin D$\_$3/ to its hydroxylated forms.