• The Korean Journal of Food And Nutrition
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• v.15 no.4
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• pp.307-313
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• 2002

The primary objective of these studies was to screen the materials showing inhibitions of HMG-CoA reductase in vitro. The secondary objective was to determine the effect of garlic, lovastatin and copper on cholesterol concentrations in plasma, liver and breast tissues in pullets. The degree of inhibition of the selective samples on HMG-CoA reductase activity was determined in vitro. The inhibition ratios of water soluble garlic extracts, lovastatin (methanol extracts) and copper to HMG-CoA reductase activity were 51.3%, 87.5%, and 82.0%, respectively. Control diet (basal diet) and experimental diets, garlic powder (3% in diet), lovastatin (300mg/Kg of diet) and copper (200mg/Kg of diet) were fed to pullets in order to investigate the changes of cholesterol concentration in plasma and tissues. Total cholesterol, HDL- and LDL-cholesterol in blood plasma were significantly reduced in pullets fed diet containing 3% garlic powder. However, copper significantly increased total cholesterol compared to control and lovastatin did not affect plasma cholesterol concentration. Total cholesterol and triglyceride of liver and breast tissues in pullets were not affected by adding the cholesterol-lowering materials to diets. The data suggests that it is not easy for HMG-CoA reductase inhibitors to reduce cholesterol levels in body due to complication of cholesterol metabolism. However, garlic administration can lower the levels of plasma cholesterol in pullets.

• 한국생물공학회:학술대회논문집
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• 2003.04a
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• pp.228-232
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• 2003

Lovastatin produced by Aspergillus terreus via polyketide pathway is a secondary metabolite with high anti-hypercholesterolemic activity. In this paper we are going to present effective strain development strategies for lovastatin production by comparing the productivity of the mutants obtained through traditional rational screening process and protoplast fusion method. Mutants resistant against various antibiotics and/or antimetabolites showed significantly higher lovastatin productivity than the corresponding mother strains, demonstrating that rational screening method was very efficient in selecting high yielding producers. Recombinant fusants obtained using protoplast fusion between high producers were observed to have very different morphology and physiology as represented by the production and secretion of lovastatin, as well as cell growth pattern. In parallel with the strain development, optimization process for the production medium was carried out in order to find optimal concentrations of the medium components using such a powerful statistical method as response surface method (RSM). It was concluded that not only the optimum production medium but also good morphological characteristics of the high-yielding producers led to higher lovastatin production.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3797-3803
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• 2016

Cervical cancer is the second most common malignancy in women worldwide and thus one of the leading causes of mortality in women. Lovastatin, a non polar, anticholesterol drug has previously been reported to exert antitumour activity in vitro. In the present study, lovastatin from Aspergillus terreus (KM017963) was purified by adsoprtion chromatography and evaluated for its anticancer and anti-oxidant properties with a human cervical cancer cell line (HeLa). Growth inhibitory and proapoptotic effects of purified lovastatin on HeLa cells were investigated by determining its influence on cell numbers, mitochondrial membrane potential (MMP), DNA fragmentation and antioxidant properties in terms of hydroxy radical scavenging effects as well as levels of total reduced glutathione. Cell cycle analysis by flow cytometry (propidium iodide staining) confirmed induction of apoptotic cell death and revealed cell cycle arrest in the G0/G1 phase. Results of the study give leads for the anticancer effects of lovastatin and its potential usefulness in the chemotherapy of cervical cancer.

• YAKHAK HOEJI
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• v.45 no.2
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• pp.220-226
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• 2001

A bioequivalence study of Lovastati $n^{TM}$ tablets (Dong Sung Pharmaceutical Co., Korea) to Mevaco $r^{TM}$ tablets (Choong Wae Pharmaceutical Co., Korea) was conducted according to the guidelines (No. 98-56) of Korea Food and Drug Administration (KFDA). Each tablet contained 20 mg of lovastatin. Eighteen healthy Korean male subjects received each formulation at a lovastatin dose of 80 mg (i.e., four tablets) in a 2 $\times$ 2 crossover study. There was a washout period of a week between the dose of the two formulations. Plasma concentrations of lovastatin acid were monitored by a GC/MS method for over a period of 12hr after each administration. The area under the plasma concentration-time curve from time zero to 12hr (AUC) was calculated by a linear trapezoidal method. The maximum plasma drug concentration ( $C_{max}$) and the time to reach $C_{max}$ ( $T_{max}$) were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) of these parameters revealed that there are no differences in AUC and $C_{max}$ between the formulations. The apparent differences between the formulations in these parameters were 4.87 and 8.03% for AUC and $C_{max}$, respectively. Minimum detectable differences (%) at $\alpha$=0.1 and 1-$\beta$=0.8 were 17.84 and 15.36% for AUC and $C_{max}$ respectively. The 90% confidence intervals were -15.30~5.56 and -17.02-0.95% for AUC and $C_{max}$, respective1y. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Mevaco $r^{TM}$ tablets and Dong Sung Lovastati $n^{TM}$ tablets are bioequivalent.ivalent.ent.alent.ent.

• Journal of Ginseng Research
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• v.20 no.3
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• pp.241-247
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• 1996

The effects of ginseng total saponin, ginsenoside-Rb, and -Rb, on the reduction of chmlesterol level and the myNA expression rates of HMG CoA reductase and LDL receptor in Hep G2 were investigated and compared with that of lovastatin, a competitive HMG CoA reductase Inhibitor. The amounts of cholesterol in Hep G2 decreased in total saponin-and ginsenoside-treated groups as compared with that of control group, while there was no significant reduction in lovastatin-treated group. The mRNA expression rates of HMG CoA reductase increased in total saponin and gin- senoside groups except for ginsenoside-Rb, (10-3%) group and decreased in lovastatin group com- pared with that of control group. The mRNA expression rates of LDL receptor generally increased In all of the test groups except for total saponin (10-5%) group compared with that of control group. Because the ginseng components tested were more effective in the reduction of cholesterol level in Hep G2 than lovastatin and induced the gene expression of LDL receptor, we suggest the possibility that they could be used as a replacement agent for lovastatin which can not be prescribed especially to patients with hepatic diseases.

• YAKHAK HOEJI
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• v.58 no.3
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• pp.171-180
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• 2014

To enhance the in vitro permeation of lovastatin through excised hairless mouse and human cadaver skins, solubility was determined in various hydrophilic and lipophilic vehicles, and the effects of vehicles and penetration enhancers on the skin permeation from solution formulations were investigated. Solubility of lovastatin was highest in N-methyl-2-pyrrolidone (NMP) ($278.2{\pm}10.1$ mg/ml) and dimethyl sulfoxide (DMSO) ($162.2{\pm}9.7$ mg/ml). Among different pure vehicles used, NMP, DMSO, propylene glycol and isopropyl myristate provided some drug permeation ($6.9{\pm}1.1$, $5.9{\pm}1.6$, $3.0{\pm}0.5$ and $2.2{\pm}0.3{\mu}g/cm^2$ at 24 hr, respectively) through hairless mouse skin. The addition of oleic acid, linoleic acid and oleyl alcohol to DMSO showed the maximum permeation at around 5 v/v%, however, capric acid and caprylic acid had no enhancing effect. The increase of enhancer concentrations showed bell-shaped permeation rate, suggesting the presence of optimal concentration in lovastatin penetration. Increasing donor concentration from 10 mg/ml to 80 mg/ml in DMSO and a cosolvent of DMSO, NMP and DGME (3 : 3 : 4 v/v) did not show significant dose dependent permeation in both hairless mouse and human cadaver skins. The maximum lovastatin flux through human cadaver skin was found to be $0.87{\pm}0.46{\mu}g/cm^2$/hr with 5 v/v% linoleic acid and donor dose of 4 mg/0.64 $cm^2$ in the cosolvent. These results suggest that transdermal delivery of lovastatin would be feasible by establishing the optimal concentrations of donor dose and unsaturated fatty acids in appropriate vehicles.

• Journal of Pharmaceutical Investigation
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• v.32 no.4
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• pp.267-275
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• 2002

A self-microemulsifying drug delivery system (SMEDDS) was developed to increase the dissolution rate, solubility, and ultimately bioavailability of a poorly water soluble drug, lovastatin. SMEDDS was thε mixtures of oils, surfactants, and cosurfactants, which emulsify under conditions of gentle agitation, similar to those which would be encountered in the gastro-intestinal (GI) tract. Various types of self-emulsifying formulations were prepared using four types of oil (Capryol 90, Lauroglycol 90, Labrafil M 1944 CS and Labrafil M 2125), two surfactants (Cremophor EL and Tween 80), and three cosurfactants (Carbitol, PEG 400 and propylene glycol). Thε efficiency of emulsification was studied using a laser diffraction size analyzer to determine particle size distributions of the resultant emulsions. Optimized formulations selected for bioavailability assessment were Carpryol 90 (40%), Cremophor EL (30%) and Carbitol (30%). SMEDDS containing lovastatin (20 mg and 5 mg) were compared to a conventional lovastatin tablet $(Mevacor^{\circledR},\;20\;mg/tab)$ by the oral administration as prefilled hard gelatin capsules to fasted beagle dogs for in vivo study. The arεa under the serum concentration-time curve from time zero to the last measured time in serum, $AUC_{0{\rightarrow}24h}$, was significantly greater in SMEDDS, suggesting that bioavailability increase 130% and 192% by the SMEDDS, respectively. The self-emulsifying formulations of lovastatin afforded the improvement in absolute oral bioavailability relative to previous data of lovastatin tablet formulation. These data indicate the utility of dispersed self-emulsifying formulations for the oral delivery of lovastatin and potentially other poorly absorbed drugs.

• Journal of Ginseng Research
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• v.28 no.2
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• pp.87-93
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• 2004

The effect of ginsenoside-Rb2, one of a major pharmacological component of Panax ginseng C.A. Meyer, on low density lipoprotein (LDL) receptor expression was investigated and compared with hypocholesterolemic drug lovastatin. In HepG2 cell, exogenous cholesterol decreased LDL receptor mRNA expression, but ginsenoside-Rb2 recovered this reduction of LDL receptor mRNA up to normal expression level. Lovastatin also increased LDL receptor mRNA expression as similar as ginsenoside-Rb2 did. The reduction of sterol regulatory element binding protein (SREBP) transcription by exogenous cholesterol was also similarly recovered by ginsenoside-Rb2 and lovastatin addition. Compound K, a metabolite of ginsenoside-Rb2 and -Rb1 by human intestinal bacteria also increased the SREBP mRNA expression in cholesterol-enriched condition. Ginsenoside-Rb2 seems to up-regulate LDL receptor mRNA expression through the induction of de novo SREBP transcription. Therefore, increased expression of SREBP mRNA by ginsenoside-Rb2 elevated the LDL receptor mRNA expression in HepG2 cells, and these inductions possibly drop the plasma cholesterol level in hypercholesterolemia patients, in vivo, as likely in case of lovastatin.

• Preventive Nutrition and Food Science
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• v.4 no.1
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• pp.70-74
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• 1999

The primary objective of these studies was to screen the materials showing inhibitions of HMG-CoA reductase in vitro. The secondary objective was to determine the effect of garlic, lovastatin and copper on cholesterol concentrations in plasma. liver and brease muscle of pullets. In experiment 1, the degree of inhibition of the selective samples on HMG-CoA reductase activity was determined in vitro. The inhibition rate of water soluble garlic extracts, lovastatin and copper to HMG-coA reductase activity were 51.3%, 87.5%, and 82.0% respectively . In experiment 2, control diet (basal diet), garlic powder (3% in diet) , lovastatin (300mg/kg of diet) and copper(200mg/kg of diet) were fed to pullets in order to investigate the changes of cholesterol concentration in plasma and tissues. Plasma total cholesterol , and LDL-cholesterol were significantly reduced in pullets fed a diet containing 3 % garlic powder. However, coper significantly increased total cholesterol compared to controls and lovastatin did not affect plasma chholesterol concentration . Total cholesterol inlover and breast muscle inpullets were not affectedb y adding cholesterol lowering materials to the diets. The data suggests that it is not easy for HMG-CoA reductase inhibitors to reduce cholesterol levels in the body due to complication in cholestrol metabolism . However, garlic administration can lower the levels of plasma cholesterol in pullets.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.332-332
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• 1994

식이습관을 바꾸지 않는 상태에서 4주간의 placebo 투여후 혈청 Total-C치가 240mg/dl 이상인 원발성 고콜레스테 혈증환자 25예씩 두군으로 하여 제1군은 lovastatin 20mg에서 80mg을 1일 1회 저녁에 12주간 투여하였고, 제2군은 pravastatin 5mg을 12주간 아침 저녁으로 2회 경구 투여하였다. Lovastatin과 pravastatin 12주 투여후 혈청 Total-C치는 309$\pm$46mg/d1에서 201$\pm$37mg/d1로, 281$\pm$41mg/d1에서 218$\pm$31mg/d1로, 혈청LDL-C치는 230$\pm$46mg/d1에서 125$\pm$40mg/d1로, 199$\pm$46mg/d1에서 137$\pm$37mg/d1로 각각 유의하게 감소 하였다. (p < 0.005)혈청 Apo B치는 183$\pm$32mg/d1에서 114$\pm$26mg/d1로, 164$\pm$38mg/d1에서 123$\pm$20mg/d1로, 혈청 Apo B / Apo A-1 ratio는 1.6$\pm$0.4에서 1.0$\pm$0.3으로, 1.4$\pm$0.5에서 1.0$\pm$0.3으로 각각 유의하게 감소하였다. (p < 0.005) Lovastatin 및 pravastatin 투여후 임상적으로 의미있는 중상이나 검사상 이상 소견은 관찰되지 않았다.