• 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 Food Science and Technology
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• v.54 no.4
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• pp.398-402
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• 2022

Black chokeberry (Aronia melanocarpa), a rich source of polyphenols, exerts hypocholesterolemic effects. However, little is known about its effects on the regulation of the hepatic cholesterol metabolism and the underlying mechanisms. In the present study, the effects of polyphenol-rich black chokeberry extract (CBE) on hepatic cholesterol metabolism were investigated by measuring the expression of genes involved in the absorption, de novo synthesis, and efflux of cholesterol in HepG2 cells. There was a significant reduction in the expression levels of genes involved in cholesterol metabolism, the low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and sterol regulatory element-binding protein 2, in CBE-treated HepG2 cells. Meanwhile, CBE increased the expression levels of genes involved in cholesterol and bile acid efflux. The expression levels of mitochondrial fatty acid oxidation genes increased, whereas those of lipogenic genes decreased following CBE treatment. These data suggest that the consumption of black chokeberry may be beneficial for the prevention of hypercholesterolemia.

• Food Science of Animal Resources
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• v.41 no.2
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• pp.343-352
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• 2021

The objective of this study was to evaluate the effects of Lactobacillus acidophilus ATCC 43121 and L. fermentum MF27 on biochemical indices in the serum, cholesterol metabolism in the liver and mucin expression in the gallbladder in lithogenic diet (LD)-induced C57BL/6J mice to determine the preventive effects of lactobacilli on gallstone formation. By the end of 4 wk of the experimental period, mice fed on a LD with high-fat and high-cholesterol exhibited higher levels of total and low-density lipoprotein cholesterol in the serum compared to mice fed on control diet or LD with L. acidophilus ATCC 43121 (LD+P1; p<0.05). Cholesterol-lowering effects observed in the LD+P1 and LD with L. fermentum MF27 (LD+P2) groups were associated with reduced expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the liver compared to the LD group (p<0.05). Furthermore, expression of the gel-forming mucin, including MUC5AB and MUC5B, was suppressed in the LD+P1 and LD+P2 groups compared to the LD group (p<0.05). Therefore, steady intake of both L. acidophilus ATCC 43121 and L. fermentum MF27 may have the ability to prevent the formation of cholesterol gallstones in LD-induced C57BL/6J mice.

• Korean Journal of Food Science and Technology
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• v.43 no.3
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• pp.375-380
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• 2011

This study was performed to investigate cholesterol improvement effects of adding fermented defatted soybean grit (FD) and FD added to 5 or 10% Corchorus olitorius (FDC). Cholesterol adsorption in the FD and FDC group was more than 70%. Apolipoprotein AI and CIII improved in HepG2 cells, and a greater improvement effect was shown in FDC than that in FD. We also investigated the effect of FDC on body lipid metabolism and a high-fat diet for 4 weeks. Rats were divided into control (Con), high-fat (HF), HF treated with 20% FD (HF-FD), and HF treated with 20% FDC (HF-FDC) groups. Plasma total cholesterol and low density lipoprotein-cholesterol concentrations, hepatic total cholesterol, and triglyceride contents were significantly lower in the HF-FDC group than those in the HF group. Additionally, fecal total cholesterol and triglyceride contents increased in rats treated with FDC. Hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activities were significantly lower in the HF-FDC group than those in the HF group.

• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.107-112
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• 1998

Lovastatin is a lipid lowering agent for the treatment of hypercholesterolemia and belongs to a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, lovastatin disrupts the biosynthesis of cholesterol in hepatic and peripheral cells and increases the synthesis of high-density-lipoprotein HDL) receptors. Following oral administration, the lactone ring of lovastatin is hydrolysed to the active inhibitor of HMG CoA reductase, lovastatin acid. Lovastatin is known to have poor oral absorption and wide individual variation. In this study, bioequivalence test of two lovastatin formulations, the test drug ($Lovaload^{TM}$, Chong Kun Dang Pharmaceutical Co.) and the reference drug ($Mevacor^{TM}$, Chung Wae Pharmaceutical Co.) were conducted according to the guidelines of Korea Food and Drug Administration (KFDA). A total of 18 healthy male volunteers, $31.90\pm3.60$ years old and $72.17\;7.88$ kg of body weight in average, were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of lovastatin acid in plasma were measured upto 12 hours following a single oral administration of eight tablets (20 mg of lovastatin per tablet) by high-performance liquid chromatography with UV detection at 238 nm. The area under the concentration-vs-time curve from 0 to 12 hours $(AUC_{0-12h})$ was calculated by the trapezoidal summation method. The statistical analysis showed that there are no significant differences in $AUC_{0-12h),\;C_{max}\;and\;T_{max}$ between the two formulations ($6.72\%,\;1.52\%,\;and\;0.88\$, respectively). The least significant differences between the formulations at $\alpha$=0.05 were less than $20\%\;(11.65\%,\;19.73\%,\;and\;14.81\%\;for\;AUC_{0-12h},\;C_{max}\;and\;T_{max}$, respectively). The $90\%$ confidence intervals for these parameters were also within $\pm20\%\;(-1.50{\leq}{\delta}{\leq}15.00$, $-12.50{\leq}{\delta}{\leq}15.50,\;and\;-9.64{\leq}{\delta]{\leq}11.40{\leq}\;for\;\;AUC_{0-12h}$ ,$C_{max}\;and\;T_{max}$, respectively). In conclusion, the new generic product $Lovaload^{TM}$ was proven to be bioequivalent with the reference drug.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.11
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• pp.1701-1708
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• 2014

Phenolic compounds, physiological properties, and digestive enzyme inhibitory effect of 70% ethanol extracts from Aster scaber with different extraction methods (stirrer extraction, SE; reflux extraction, RE; autoclave extraction, AE; low temperature high pressure extraction, LTPE; ultrasonification extraction, USE) were investigated. Total polyphenols and flavonoids contents in LTPE were significantly higher than those of other extracts. The amount of substances related to cynarin (1,3-O-dicaffeoylquinic acid) was highest in USE (34.34 mg/g), followed by LTPE (33.83 mg/g), RE (32.27 mg/g), AE (25.40 mg/g), and SE (18.17 mg/g). Chlorogenic acid (5-O-caffeoylquinic acid) and astragalin (kaempferol-3-O-glucopyranoside) were highest in AE and LTPE, respectively. Xanthine oxidase, angiotensin- I converting enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase and acetylcholin esterase inhibitory activities of LTPE and USE at a concentration of 50 mg% (w/v) were somewhat higher than those of other extracts. The ${\alpha}$-amylase, ${\alpha}$-glucosidase, trypsin and lipase activities showed the same tendency as physiological properties (concentration of 500 mg%, w/v). Additionally, there was significantly higher or slightly lower inhibitory activity compared to the control group. These results suggest that extracts from Aster scaber have potential to act as functional materials, and LTPE and USE are superior for the enhancement of biological activity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.5
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• pp.826-833
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• 2002

This study was conducted to investigate the effects of YK-209 mulberry leaves on HMG-CoA reductase activity and lipid composition of liver in streptozotocin-induced diabetic rats. Sprague-Dawley male rats weighing 100 $\pm$ 10 B were randomly assigned as a normal group and four STZ-induced diabetic groups according to the level of dietary mulberry leaves supplement. The experimental diets were fed ad libidum, so that diabetes was experimentally induced by intravenous injection of STZ 55 mg/kg of body weight after feeding for 3 weeks. Animals were sacrificed on the 9th day of diabetic states. The levels of serum triglyceride, total-cholesterol and LDL-cholesterol in DM group were higher than mulberry leaves supplemented groups and normal group, but those of the mulberry leaves supplemented groups were significantly decreased to normal level. In contrast, the leavels of serum HDL-cholesterol in DM group was significantly reduced than that of normal group, but mulberry leaves supplemented groups were increased to normal level. Atherogenic index in DM group was higher about 3 fold than the normal group but the DM-0.1Y and DM-0.2Y groups were maintained the normal level. Contents of total lipid and triglyceride of liver in DM group were significantly lower than that of normal group, but the mulberry Leaves supplemented groups increased than that of DM group. The contents of hepatic cholesterol in DM group was 160% higher than that of normal group, but the mulberry leaves supplementation groups maintained the normal level. The activity of hepatic 3-hydroxy -3-methylglutaryl Coenzyme A (HMG-CoA) reductase in DM group was 43% lower than that of normal group, but had no significant difference between DM-0.1Y, DM-0.2Y and normal groups. In conclusion, YK-209 mulberry loaves has improving effect of the lipid metabolism in STZ-induced diabetic rats through hepatic HMG-CoA reductase activity, and the change of lipids contents in serum and liver.

• Journal of Life Science
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• v.31 no.4
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• pp.418-424
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• 2021

Skin inflammation (dermatitis) is caused by varying skin damage due to ultraviolet radiation and microbial infection. Currently prescribed drugs for dermatitis include anti-histamine and steroid drug classes that soothe inflammation. However, incorrect or prolonged use of steroids can cause weakening of skin barriers as well as osteoporosis. Therefore, treating dermatitis with a drug that has minimal side effects is important. Statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are cholesterol-lowering drugs that have been widely treated for hyperlipidemia and cardiovascular diseases. Interestingly, recent studies have shown the anti-inflammatory effects of statins in both experimental and clinical models for of osteoarthritis. This study investigated the possible anti-inflammatory effects of atorvastatin and fluvastatin in human keratinocytes (HaCaT cells), which are crucial components of skin barriers. Stimulation of HaCaT cells with IL-1β increased the expression of the COX2 protein, a major player of inflammatory responses. However, this induction of the COX2 protein was downregulated by pretreatments with atorvastatin and fluvastatin. Treatment with IL-1ß-induced the upregulation of other inflammatory genes (such as iNOS and MMP-1) and these expressions were similarly lowered by these two statin drug treatments. Taken together, these results indicated that atorvastatin and fluvastatin can reduce IL-1β-induced inflammatory responses in HaCaT cells. In conclusion, the findings suggest that atorvastatin and fluvastatin can be potential modulators for ameliorating skin inflammation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.6
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• pp.861-868
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• 2013

This study investigated the effects of Opuntia ficus-indica and other natural resources (OF) in db/db and C57 mice. Plasma triglycerides, cholesterol, alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, fecal bile acid excretion, the histopathological appearance of the liver, and cholesterol-related mRNA expression were determined. Mice (12 db/db mice and 12 C57 mice) were assigned to diabetic-control (db-C), diabetic-OF treatment (db-OF), normal-control (C57-C), and normal-OF treatment (C57-OF) groups. Animals in the control group were fed an AIN-76 recommended diet and animals in the OF group were fed an experimental diet containing 5% of OF for 4 weeks. Concentrations of total plasma cholesterol, triglyceride, low density lipoprotein (LDL)-cholesterol, and very low density lipoprotein (VLDL)-cholesterol decreased with the administration of OF. In contrast, high density lipoprotein (HDL)-cholesterol levels were minimally affected by the experimental diet. Plasma AST and ALT showed lower activities in the db-OF group, and the fecal excretion of bile acid was reduced in the db-OF group. Histopathological analysis of the liver showed that fatty liver conditions in the db-OF group were more improved than db-C. Low-density lipoprotein receptor (LDL-R) and cholesterol 7${\alpha}$-hydroxylase (CYP7A1) mRNA expression were increased in the db-OF group as well. However, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA-R) mRNA expression was lower in the db-OF group. These results provide experimental evidence about improved lipid metabolism of the OF feeding in the db/db mice.

• Journal of Life Science
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• v.29 no.10
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• pp.1144-1151
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• 2019

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with various metabolic syndromes, such as obesity, dyslipidemia, hypertension, and diabetes. Cudrania tricuspidata is a medicinal plant distributed widely in Asia and has been used in clinical practice to treat various diseases. The aim of this study is to determine the lipid-lowering effects of C. tricuspidata fruit extract (CTE) using a cell model induced by free fatty acids (FFAs). HepG2 cells were exposed to 1mM FFAs (palmitic acid:oleic acid = 2:1) for 24 hr to simulate the conditions of NAFLD in vitro. CTE attenuated the increases of lipid accumulation, intracellular triglyceride, and cholesterol content and inhibited 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) activity in the HepG2 cells in a dose-dependent manner. Also, CTE inhibited the protein expression of lipogenesis-related genes, such as sterol regulatory element-binding protein-1/-2 (SREBP-1/-2), fatty acid synthase (FAS), and stearoyl CoA desaturase-1 (SCD-1) in FFAs-induced lipid accumulation in HepG2 cells. In addition, CTE-induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in HepG2 cells. These results suggest that CTE attenuates hepatic lipid accumulation by inhibiting lipogenesis through the modulation of the AMPK signaling pathway on FFAs-induced lipogenesis in HepG2 cells and may potentially prevent NAFLD.