• 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.

• 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.

• Development and Reproduction
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• v.11 no.2
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• pp.59-66
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• 2007

Understanding molecular mechanisms that control embryonic stem cell (ESC) self-renewal and differentiation is important for the development of ESC-based therapies. Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), potently reduce cholesterol level. As well as inhibiting cholesterol synthesis, statins inhibit other intermediates in the mevalonate pathway such as farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), major substrates for protein isoprenylation. Studies showed that pleiotropic effects of statins beyond cholesterol lowering property arise from inhibition of protein isoprenylation that is involved in various cellular functions including proliferation and differentiation. It has been determined that statins have inhibitory effect on ESC self-renewal and stimulatory effect on ESC differentiation into adipogenic/osteogenic lineages. Importantly, statins mediate downregulation of ESC self-renewal by inhibiting RhoA-dependent signaling, independently of their choresterol-lowering properties. Understanding statin's actions on ESCs may provide important insights into the molecular mechanisms that regulate self-renewal or differentiation of ESCs.

• YAKHAK HOEJI
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• v.57 no.1
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• pp.24-31
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• 2013

Although statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have been shown to increase melanin synthesis, the exact mechanism of this action is not fully understood. In this study we investigated the possible involvement of intracellular $Ca^{2+}$ signal in the mechanism of stimulation of melanin synthesis induced by lovastatin in B16 cells. Lovastatin stimulated the production of melanin in a dose-dependent manner in the cells. Treatment with mevalonate, FPP and GGPP, precursors of cholesterol, did not significantly suppress the lovastatin-induced melanin production, suggesting that inhibition of cholesterol synthesis may not be involved in the mechanism of the action of lovastatin. In addition, lovastatin did not significantly alter the cAMP concentration and the stimulated production of melanin by lovastatin was not significantly changed by treatment with H89, a potent inhibitor of protein kinase A, which demonstrates that cAMP pathway may not be involved. However, lovastatin increased intracellular $Ca^{2+}$ concentration in a dose-related fashion. Treatment with EGTA, an extracellular $Ca^{2+}$ chelator did not significantly alter the lovastatin-induced intracellular $Ca^{2+}$ increase and melanin synthesis, whereas intracellular $Ca^{2+}$ reduction with BAPTA/AM and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8) completely blunted these actions of lovastatin. Taken together, these results suggest that the intracellular $Ca^{2+}$ release may play an important role in the lovastatin-induced stimulation of melanin synthesis in B16 cells. These results further suggest that lovastatin may be useful for the treatment of hypopigmentation disorders, such as vitiligo.

• Journal of Life Science
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• v.28 no.6
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• pp.726-732
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• 2018

The purpose of this study was to investigate the effects of Bacillus polyfermenticus KJS-2 (B. polyfermenticus KJS-2) and Angelica gigas Nakai extracts (AGNE) on hyperlipidermia. The purity of the major decursin and decursinol angelate (D/DA) in the AGNE were analyzed at 78%. Increased concentrations of AGNE (0.1-20 mg/ml) showed a higher 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibition activity. Endospore-forming B. polyfermenticus KJS-2 ($1{\times}10^9CFU/ml$) exhibited good bile tolerance (0.3 mm) on an agar plate. An animal study was carried out using different groups, including a normal control, positive control (atorvastatin), negative control (triton WR-1339), AGNE group, B. polyfermenticus KJS-2 group, AGNE + B. polyfermenticus KJS-2 group, and Atorvastatin + AGNE + B. polyfermenticus KJS-2 group to determine the effect of hyperlipidemia. There were no significant changes in body weight, kidney weight, or liver weight except for the liver weight of the triton WR-1339-treated group. Groups with AGNE and B. polyfermenticus KJS-2 had increased HDL-cholesterol and decreased total cholesterol and triglycerides. The liver histopathological results also showed that all AGNE and B. polyfermenticus KJS-2-treated groups contained lower fat accumulation in the liver tissues. The findings of this study verified that AGNE and Endospore-forming B. polyfermenticus KJS-2 combination materials have a hyperlipidemic effect.

• 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.

• Food Science and Preservation
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• v.12 no.6
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• pp.624-630
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• 2005

Plantain was extracted with ethanol and fractionated systemically with n-hexane, chloroform, ethylacetate, n-butanol and water to study inhibitory effect on cholesterol synthesis in vitro. To screen the effect, inhibitory activities on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase obtained from Saccharomyces cerevisiae were examined using the five fractions of Plantain. The HMG-CoA reductase activity was inhibited most by ehylacetate fraction among the fractions, although the all five fractions had the effect To see the hypocholesterolemic effect of the ethylacetate fraction of Plantanin (PAE) in vivo, male Sprague-Dawley rats were received 5 types of diets for 6 weeks: normal diet group (NOR), high cholesterol diet group($1\%$ cholesterol and $0.25\%$ sodium cholate, CON), normal diet and PAE 70 mg/kg administered group(S1), high cholesterol diet and PAE 140 mg/kg administrated group(S2), and high cholesterol diet and PAE 140 mg/kg administered group(S3). Body weight gains of the CON were significantly increased compared to those of S1, S2 and S3. Activities of serum AST and ALT were tended to be increased in CON compared with NOR and reduced by the PAE administration. Concentrations of serum total cholesterol, free cholesterol, LDL-cholesterol, triglyceride and the atherogenic index were tended to be decreased in the PAE administered groups compared with the CON. HDL-cholesterol and phospholipid concentrations were significantly decreased in the CON and markedly increased by the PAE administered groups. Taten together, it is suggested that the ethylacetate fraction of Plantanin exerts antiatherosclerotic effect by reducing serum cholesterol concentrations in rats fed high cholesterol diets.

• Food Science and Preservation
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• v.13 no.5
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• pp.634-642
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• 2006

This study was performed to investigate the effects of lotus root ethanol extinct (LRE) on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in vitro, and lipid metabolism in the serum and liver of rate fed normal or high cholesterol diet in vivo. LRE (200 mg/kg/day and 400 mg/kg/day) was administered only to rats with fed high cholesterol diet for 6 week. We divided into 6 groups: normal diet group (NC), high cholesterol diet group (1% cholesterol and 0.25% sodium cholate)(HC), LRE 200 mg/kg treated group (NC-LREL), LRE 400 mg/kg teated group (NC-LREH), high cholesterol diet and LRE 200 mg/kg treated group (HC-LREL), and high cholesterol diet and LRE 400 mg/kg teated group (HC-LREH). LRE significantly inhibited the HMG-CoA reductase activity in a concentration-dependent manner in vitro. The body weight gain and liver weight of the high cholesterol diet group were higher than the normal diet group whereas the groups administered LRE were gradually decreased. The high cholesterol diet group increased serum triglyceride, total cholesterol, free cholesterol and LDL-cholesterol levels, and decreased atherogenic index, HDL-cholesterol and phospholipid levels as compared with the normal diet group. LRE administrated groups were increased in serum HDL-C/T-C, HDL-cholesterol and phospholipid levels, and decreased serum triglyceride, total cholesterol, free cholesterol, and LDL-cholesterol levels as compared with the high cholesterol diet group. These effect of LRE within the high cholesterol diet groups were concentration-dependent manners. There were no differences in the levels of serum triglyceride, total cholesterol, phopholipid, HDL-cholesterol and free cholesterol between normal diet groups. The hepatic LRE administrated groups than in the high cholesterol diet group. Teken together, it is suggested that LRE exerts hypocholesterolemic effect by reducing serum cholesterol concentration in rats with high cholesterol diet-induced hypercholesterolemia.

• Journal of Korean Medicine Rehabilitation
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• v.30 no.1
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• pp.1-12
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• 2020

Objectives Depletion of ovarian function after menopause in women induces estrogen deficiency leading to increased fat and decreased muscle mass. In this study, we examined the effect of herbal medicines by measuring hormone expression in muscle tissue of estrogen-deficient rats induced by ovariectomy. Methods Ovariectomy was performed to induce estrogen deficiency, and mice were given herbal prescription (HP) for 6 weeks. Estrogen-deficient rats were divided into two groups: one group (HPH) which were orally administered HP 200 mg/kg and the other group (HPL) administered HP 40 mg/kg. Weight changes in both groups were measured using polymerase chain reaction (PCR). After extraction of the femoral muscles in mice, the expression of the leptin, lipoprotein lipase (LPL), diacyl glycerol acyltransferase (DGAT)1, peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, NADH dehydrogenase (NDH), farnesyl diphosphate farnesyltransferase (FDFT)1, lanosterol synthase (LSS), phosphatidylethanolamine N-methyltransferase (PEMT), and peroxiredoxin (Prdx6) were measured using PCR. Results HP increased the expression of leptin, LPL, DGAT1, PGC-1α, NDH, FDFT1, LSS, PEMT, and Prdx6. HP affects body fat metabolism and is effective in improving menopausal obesity and obesity complications caused by estrogen deficiency. However, HP does not affect the expression of tumor necrosis factor-α and 3-hydroxy-3-methylglutaryl-CoA reductase, and thus will not be effective in obesity-related metabolic diseases. Conclusions HP is thought to inhibit weight gain by regulating hormone expression related to glucose metabolism and lipid metabolism in muscle tissue of estrogen-deficient rats.

• Journal of Korean Medicine for Obesity Research
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• v.14 no.2
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• pp.47-54
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• 2014

Objectives: This study is to confirm the effect of combined extract and individual extract of Samjunghwan (SJH) in anti-oxidative and anti-obesity effect. Methods: Combined ethanol extract of readily made SJH and individual ethanol extract of Atractylodes japonica, Cortex lycii radicis, and Morus alba Linne was combined after the extraction. To evaluate the anti-oxidative effect of SJH, total phenol compound and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging ability were conducted. Real-time quantitative-polymerase chain reaction analysis of transcription factor peroxisome proliferator-activated receptror ${\gamma}$ ($PPAR{\gamma}$), adenosine monophosphate-activated protein kinase (AMPK)-${\alpha}1$, tumor necrosis factor-${\alpha}$ ($TNF{\alpha}$) and 3-hydroxy-3-methylglutaryl CoA reducatase (HMG-CoA reductase) were done with 3T3-L1 cells to investigate the ant-obesity effect. Also, cell viability analysis were done to see to toxicity of SJH. Results: Individual extract of SJH showed significant decrease in $TNF{\alpha}$ and AMPK transcription while $PPAR{\gamma}$ showed significant increase. Combined extract and individual extract of SJH both showed decrease in HMG-CoA reductase. DPPH free radical scavenging ability and total phenol compound was analogous between two groups. Conclusions: Individual extract of SJH appears to be more effective in anti-oxidation and anti-obesity effect compared to combined extract of SJH.