• The Korea Journal of Herbology
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• v.33 no.5
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• pp.89-103
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• 2018

Objectives : This study is aimed to compare the changes in Antioxidative capacity of Liriopis Tuber by steaming process and to compare the effects in hyperlipidemia induced rats fed high cholesterol diet between Simvastatin and Liriopis Tuber by steaming process. Methods : The SD rats were divided into six groups: normal diet (Nor), high cholesterol diet (Veh), high cholesterol diet plus Simvastatin 5 mg/kg (Sim), high cholesterol diet plus LT0 extract 200 mg/kg (LT0), high cholesterol diet plus LT6 extract 200 mg/kg (LT6) and high cholesterol diet plus LT9 extract 200 mg/kg (LT9). We compared the total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL) contents and reactive oxygen species (ROS) from each serums. Protein expression in liver tissues related to antioxidant and cholesterol was analyzed. Results : The Antioxidant activity of Liriopis Tuber increased by steaming process. In vivo, TC, TG, LDL-c, atherogenic index (AI) and cardiac risk factor (CRF) decreased and HDL-c increased with increasing steaming frequency. aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and blood urea nitrogen (BUN) decreased with increasing steaming frequency. ROS decreased only in LT9, and SOD, catalase and glutathione peroxidase (GPx) increased with increasing steaming frequency. phospho-AMP-activated protein kinase (p-AMPK) increased and sterol regulatory element-binding protein 2 (SREBP-2), Phospho-Acetyl-CoA Carboxylase (p-ACC) and HMG-CoA reductase (HMGCR) decreased with increasing steaming frequency. Liver staining showed a decrease in hepatic fat accumulation of LT9. LT9 showed significant results in all experiments. Conclusions : LT9 showed significance of anti-lipid effect and improved fatty liver of hyperlipemia induced rats fed on high cholesterol diet, In conclusion, LP9 can be effectively used for the treatment of hyperlipidemia.

• Proceedings of the Materials Research Society of Korea Conference
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• 2009.11a
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• pp.38.2-38.2
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• 2009

Regeration of natural tissuesor to create biological substitutes for defective or lost tissues and organs through the use of cells. In addition to cells and their porous, drugs are required to promote tissue regeneration. Therefore, the present studies were prepared using simvastatim loaded porous poly(lactide-co-glycolide) (PLGA) by double emulsion solvent evaporation water-in-oil-in-water technique (W/O/W) as drug delivery system strategies for injuring tissue. The resulting microspheres were evaluated for morphology, particle size, encapsulation efficiency, degradation of PLGA microspheres in vitro drug release and in vitro cell viability. Scanning electronic microscopic (SEM) showed that the porosities of the particles was changed by experimental conditions and cultured cells were attached well on porous microspheres surface. The X-ray diffraction (XRD) and differential scanning calometry (DSC) analysis indicate thatsimvastatim was highly dipersed in the microsphere at amorphousstate.

• Korean Journal of Clinical Pharmacy
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• v.27 no.2
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• pp.105-112
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• 2017

Background: Generic medications are approved on the basis of bioequivalence with brand medications in healthy volunteers rather than the target population, there remains a substantial uncertainty regarding their clinical effectiveness and safety. The object of this paper is to compare the clinical equivalence of generic statin drugs in patients. Methods: Literature published before September 2016, which is indexed in PubMed, EMBASE, RISS, comparing generic to brand products in statins. Outcomes included blood lipid level, proportion of days covered (adherence), hospitalization and mortality. Results: 511 citations were screened, of which 11 studies met eligibility criteria (6 randomized clinical trials, 5 observational studies). Generic atorvastatin was clinical equivalent with brand drugs in blood lipid level (3 RCTs) and generic simvastatin was also clinical equivalent with brand drugs (2 RCTs). 2 of 3 studies reported no significant difference in proportion of days covered except 1 study which reported generic statin significantly enhance proportion of days covered (p<0.001). Hospitalization was no significant difference in all studies (p>0.05). 1 study reported that all cause of mortality was significantly low in generic drugs (p<0.0001). Conclusion: Published data on comparing clinical efficacy of generic and brand statins were insufficient in both quantity and quality. This systematic review suggests that additional studies on clinical equivalence and safety of generic medications in patients would be needed.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.177-182
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• 2014

This study was to determine the correlation between endothelial function and neuro-endocrine-immune (NEI) network through observing the changes of NEI network under the different endothelial dysfunction models. Three endothelial dysfunction models were established in male Wistar rats after exposure to homocysteine (Hcy), high fat diet (HFD) and Hcy+HFD. The results showed that there was endothelial dysfunction in all three models with varying degrees. However, the expression of NEI network was totally different. Interestingly, treatment with simvastatin was able to improve vascular endothelial function and restored the imbalance of the NEI network, observed in the Hcy+HFD group. The results indicated that NEI network may have a strong association with endothelial function, and this relationship can be used to distinguish different risk factors and evaluate drug effects.

• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.386-395
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• 2010

Bone marrow-derived mesenchymal stem cells (BM-MSC) are a multipotent cell population that can differentiate into neuron-like cells. Previously it has been reported that murine BM-MSC can differentiate into neuron-like cells by co-treatment with a Rho-associated kinase (ROCK) inhibitor -Y27632 and $CoCl_2$. In this study, we compared several ROCK inhibitors for the ability to induce human BM-MSCs to differentiate into neuron-like cells in the presence of $CoCl_2$. Y27632 with high specificity for ROCK at 1-30 ${\mu}M$ was best at inducing neuronal differentiation of MSCs. Compared to HA1077 and H1152, which also effectively induced morphological change into neuron-like cells, Y27632 showed less toxicity even at 100 ${\mu}M$, and resulted in longer multiple branching processes at a wide range of concentrations at 6 h and 72 h post-induction. H89, however, which has less specificity by inhibition of protein kinase A, S6 kinase 1 and MSK1 with similar or greater potency, was less effective at inducing neuronal differentiation of MSCs. Simvastatin, which can inhibit Rho, Ras, and Rac by blocking the synthesis of isoprenoid intermediates, showed little activity for inducing morphological changes of MSCs into neuron-like cells. Accordingly, the expression patterns for neuronal cell markers,including ${\beta}$-tubulin III, neuron-specific enolase, neurofilament, and microtubule-associated protein, were consistent with the pattern of the morphological changes. The data suggest that the ROCK inhibitors with higher specificity are more effective at inducing neuronal differentiation of MSCs.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.191-197
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• 2002

Polymer based physical mixtures or solid dispersions containing solubilizing compositions[OA, tween80 and SLS] were prepared using a spray-dryer. Lovastatin(LOS), simvastatin(SIMS), aceclofenac(AFC) and cisapride(CSP) were selected as poorly water-soluble drugs. Dextrin, poly(vinylalcohol) (PVA), poly(vinylpyrrolidone)(PVP) and polyethylene glycol(PEG) were chosen as solubilizing carriers for solid dispersions. The solid dispersions containing solubilizing compositions without drug were prepared without using organic solvents or tedious changes of formulation compositions. This system could be used to quickly screen the dissolution profiles of poorly water-soluble drugs by simply mixing with drugs thereafter. In case of solid dispersion containing drug, organic solvent systems could be used to solubilize model drugs. The dissolution rates of the drugs were higher when mixed with drug and solid dispersions containing solubilizing compositions. However, solid dispersions of LOS, AFC, and CSP simultaneously containing drug and solubilizing compositions in organic solvent systems were more useful than physical mixtures of drug and solid dispersions without drug except SIMS. Based on solubilizing capability of polymer based physical mixtures in gelatin hard capsules, optimal solid dispersion system of poorly water-soluble drugs could be formulated. However, it should be noted that dissolution rate of poorly water-soluble drugs were highly dependent on drug properties, solubilizing compositions and polymeric carriers.

• Biomolecules & Therapeutics
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• v.16 no.1
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• pp.46-53
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• 2008

The preventive hypolipidemic effect of the aqueous extracts of Picrorrhiza Rhizoma (PR) was observed in a high fat diet (HFD) feeding hyperlipidemic mouse with their hepatoprotective effects. PR extracts (50, 100 and 200mg/kg) were orally dosed once a day for 12 weeks initiated with HFD supply, and changes on body weight and gains, liver weight, serum aspartate transferase (AST) and alanine transferase (ALT) levels were monitored with serum low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride and total cholesterol levels. The efficacy of test articles was compared to that of 10mg/kg of simvastatin (SIMVA). Dramatic decrease of both absolute and relative liver weight was dose-dependently observed in all PR extract dosing groups as compared with HFD control group. The serum AST and ALT levels were dose-dependently decreased in PR extract dosing groups. The serum LDL, triglyceride and total cholesterol levels were dose-dependently decreased in PR extract dosing groups compared to that of HFD control group. The serum HDL levels were slightly but dose-dependently increased in PR extract dosing groups as compared with control group. The efficacy on the serum lipid levels of PR extracts was slighter than that of SIMVA. Based on these results, it is concluded that water extract of PR has a relatively good favorable preventive effects on the HFD inducing hyperlipidemia and hepatopathy.

• Biomolecules & Therapeutics
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• v.15 no.3
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• pp.162-168
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• 2007

It is well known that oxidized low-density lipoprotein (oxLDL) is the most characterized humoral factor that plays an important role in the pathogenesis of atherosclerosis. The water extract of the Korean herbal remedy, ZoaGumHwan (ZGH), which is composed of roots of Coptis chinensis Franch and fruits of Evodia officinalis Dode with the ratio of 6 to 1, reduced the in vitro oxidation of low density lipoproteins (LDL). Also, the ZGH extract and berberine, one of the major components of ZGH, significantly prevented oxLDL-induced adhesion of monocytes to human umbilical vein endothelial cells (HUVEC). Furthermore, the ZGH water extract and berberine decreased oxLDL-induced expression of CC chemokine receptor 2 (CCR2), a dominant monocyte chemotaxis receptor, in U937 human monocytic cells. The protective effects of the ZGH water extract and berberine were similar to those of simvastatin, an effective lipid-lowering drug. The results suggest that Korean herbal remedy, ZGH, seems to have protective effect against oxLDL-induced monocyte chemoattractant protein (MCP)-1/CCR2-dependent monocyte recruitment onto endothelial cells.

• YAKHAK HOEJI
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• v.42 no.5
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• pp.473-479
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• 1998

Lovastatin (LOVA), a fungal metabolite isolated from cultures of Aspergillus terreus, is a competitive HMG-CoA reductase inhibitor used for the treatment of primary hyper cholesterolemia, and has also been shown to suppress growth in a variety of non-glioma tumor cell lines. A sensitive reversed-phase high-perfonnance liquid chromatographic method with ultraviolet (UV) absorbance detection has been developed to quantitate LOVA in human plasma and urine samples using liquid-liquid extraction procedure. Baseline separation of LOVA and internal standard, simvastatin was achieved on a Novapak $C_{18}$ analytical column with a mobile phase containing 0.025M $NaH_2PO_4$: CAN (35:65, v/v%), adjusted pH to 4.5. The flow rate was set at 1.5ml/min, and the column effluent was monitored by a UV detection at 238nm. The limit of quantification was determined to be 0.5${\mu}$g/ml while extraction efficiency of LOVA ranged from 73.4-82.9% at LOVA concentrations of 0.5 to 10${\mu}$g/ml. Good linearity with correlation coefficients greater than 0.999 was obtained in the range of LOVA concentrations from 0.5 to 10${\mu}$g/ml. The accuracy and the precision were proven excellent with relative standard deviation (RSD, %) and relative error (RE, %) of less than 4.2 and 4.0, respectively. Intraday precision, evaluated at five LOVA concentrations (0.5, 1, 2, 5, 10${\mu}$g/ml) and expressed as RSD ranged from 0-1.82% while the interday precision at the same concentrations ranged from 0.7-10.5%. The analytical method described was then successfully employed for the determination of LOVA concentrations in plasma samples obtained during a phase II clinical trial using high doses of LOVA (30-40mg/kg/day). This method could be further utilized for the ongoing pharmacolkinetic studies and therapeutic drug monitoring of the high-dose LOVA therapy in adenocarcinoma patients.

• The Korea Journal of Herbology
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• v.35 no.4
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• pp.45-50
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• 2020

Objective : This study was performed to evaluate the toxicity after a single oral administration of black raspberry extract to male and female Sprague-Dawley (SD) rats and to determine the approximate lethal dose (ALD). Methods : We previously showed that the black raspberry extract repressed the simvastatin-mediated expression of Proprotein convertase subtilisin/kexin type 9 (PCSK9) and improved Low-Density Lipoprotein cholesterol (LDL-C) uptake by hepatocytes through the induction of the Low-Density Lipoprotein Receptor expression in hepatocytes. The groups consisted of black raspberry extract groups, as an oral dose of 2,000 mg/kg and a control group. 5 weeks SD rats were randomly assigned to 4 groups of 5 rats. Each male and female SD rats were administered orally once. For 14 days after the administration, mortality, clinical signs, changes in body weight, and necropsy findings were observed according to the "Standard for Toxicity Study of Pharmaceuticals" of Korea Food and Drug Administration (KFDA) guideline and "Acute Oral Toxicity- Fixed Dose Procedure" of OECD Test Guideline. Results : There were no cases of mortality in the group administered with 2,000 mg/kg of male and female, and no abnormalities in body weight change and clinical signs. Also, no gross abnormalities were observed at the autopsy. Conclusions : As a result of a single oral administration of the black raspberry extract to SD rats, the ALD was determined to exceed 2,000 mg/kg for both male and female SD rats.