• Journal of Microbiology and Biotechnology
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• 제21권7호
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• pp.766-775
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• 2011

We investigated the effect of high molecular weight polygamma- glutamic acid (hm ${\gamma}$-PGA) on adiposity and lipid metabolism of rats in the presence of an obesity-inducing diet. Thirty-two Sprague-Dawley rats were fed either a normal-fat (11.4% kcal fat, NFC) or high-fat (51% kcal fat, HFC) diet. After 5 weeks, half of each diet-fed group was treated with hm ${\gamma}$-PGA (NFP or HFP) for 4 weeks. The HFC group had significantly higher body weight, visceral fat mass, fasting serum levels of total cholesterol, LDL cholesterol, and leptin, and lower serum HDL cholesterol level compared with those of the NFC group (p < 0.05). Treatment with hm ${\gamma}$-PGA decreased body weight gain and perirenal fat mass (p<0.05), fasting serum total cholesterol, and mRNA expression of glucose-6- phosphate dehydrogenase (G6PD), regardless of dietary fat contents (p < 0.01). However, hm ${\gamma}$-PGA increased serum HDL cholesterol in the HFC group (p < 0.05). In vitro, 3-hydroxy-3-methylglutaryl coenzyme-A (HMGCoA) reductase activity was suppressed by the addition of hm ${\gamma}$-PGA. In agreement with observations in animal study, the supplementation of hm ${\gamma}$-PGA (150 mg/day) to 20 female subjects in an 8-week double-blind, placebocontrolled study resulted in a tendency to decrease total cholesterol and LDL cholesterol concentrations. We thus conclude that dietary supplementation of hm ${\gamma}$-PGA may act as a hypocholestrolemic agent, secondary to its inhibitor effect on HMG-CoA reductase, and decrease abdominal adiposity by decreasing hepatic lipogenesis. The present study is an important first step in establishing the effect of hm ${\gamma}$-PGA on cholesterol levels in rats and humans.

• 한국식품영양학회지
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• 제23권2호
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• pp.226-232
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• 2010

새로운 항치매성 건강식품을 개발하기 위해 아세틸콜린에스터레이즈(AChE)를 강력하게 저해하는 추출물을 곡류와 두류의 다양한 추출물로부터 선발한 후 최적 추출 조건을 조사하였다. 추출물 중 수수 메탄올 추출물이 63.4%의 가장 높은 AChE 저해 활성을 보였다. 수수를 80% 메탄올로 $40^{\circ}C$에서 12시간 추출했을 때 최대의 AChE 저해 활성을 나타내었다. AChE를 저해하는 수수 메탄올 추출물의 영양성과 생리 기능성을 조사하였다. 메탄올 추출물은 유리당으로 고형물 100 g당 4.78 g의 포도당과 4.13 g의 자당 및 0.97 g의 과당을 함유하였다. 또한, 수수 메탄올 추출물의 고형물 100 g에 linoleic acid 273.82 mg, oleic acid 215.65 mg, palmitic acid 122.03 mg, stearic acid 4.96 mg을 함유하고 있었고, 주요 유기산으로 주석산 27.45 mg, 말론산 15.43 mg, 사과산 9.94 mg이 메탄올 추출물 1 g에 함유되어 있었다. 수수 메탄올 추출물은 항치매 활성 외에도 콜레스테롤 합성을 저해하는 HMG-CoA reductase 저해 활성이 50.2%이었고, 항산화 활성은 56.1%를 보였다.

• 생명과학회지
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• 제12권1호
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• pp.106-112
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• 2002

췌장에서 분비되는 콜레스테롤 에스터레이즈(pCEase)와 소장의 acyl coenzyme A:cholesterol acyltransferase (ACAT)는 흡수된 콜레스테롤을 다시 ester화하는데 관여한다. 한방재료 중 순환촉진작용 및 건위작용 등을 가지는 계피(Cinnamomi cortex)의 에탄올 추출물이 in vitro에서 pCEase 활성에 대하여 강한 저해작용을 보였으며 에탄올 추출물의 용매분획 중 클로로포름분획이 다른 분획들, 즉 에틸 아세테이트분획, 부탄올분획 및 물 분획보다 저해활성이 강하였다. 계피의 클로로포름분획이 고콜레스테롤식 이를 섭취시킨 rat에서 혈중 콜레스테롤치를 저하시키는 효과가 있는지 측정한 실험에서 클로로포름분획을 150 mg/kg 섭취시켰을 경우 고콜레스테롤식이만은 투여한 대조군에 비하여 총cholesterol 함량이 25.1% 감소하였으며, HDL-cholesterol 함량도 33.4$\pm$1.82 g/dl로 정상군 수준으로 회복되었고 동맥경화지수 역시 현저하게 감소된 것으로 나타났다. 콜레스테롤 생합성에 관여하는 효소인 HMG-CoA reductase 활성을 측정한 결과, 고콜레스테롤 식이에 의해 감소되었던 활성이 계피 클로로포름분획의 투여량을 증가시킬수록 증가하였으나 150 mg/kg 투여군 에서도 정상군에 비하여 유의적인 감소를 보였다. 또한 계피 클로로포름분획의 독성검사 결과, mouse에서 LD$_{50}$ 은 1,300 mg/kg으로 산출되었다.

• 대한치과의사협회지
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• 제46권9호
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• pp.563-573
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• 2008

Purpose : The purpose of this study is to investigate the effects of Simvastain, which is HMG-CoA reductase inhibitor, on proliferation and differentiation of osteoblast. Materials & Methods : Twenty-four cell culture plates containing essential medium were seeded with UMR-106 cell lines, at density of 5 x $10^4$ cells per plate. Each plates were incubated with 5% $CO^2$incubator $37^{\circ}C$. Starting from 2 days after incubation, cell culture medias were replaced with Osteogenesis induction media every 2 days, for 12 days. In some plates, 0.01, 0.1, 1, 10, $100\muM$ of Simvastatin were added with Osteogenesis induction media, and classified as "test group". Those not added with Simvastatin were classified as "control group". Results : 1. When Alrizarin Red staining was observed with naked eye, control group showed normal deep red color, but test group show rapid decrease of red color as Simvastatin concentration increased more than $0.1\muM$. 2, When observed with microscope, compared to control group, amount of osteo matrix stained with Alrizarin Red decreased rapidly in Simvastatin concentration more than $0.1\muM$. 3. In optical density analysis, regarding control group as a basis, mineral deposition decreased rapidly when Simvastatin concentration increased more than $0.1\muM$. 4. In flow cytometry analysis, survival rate of UMR-106 cell showed no changes in both control group and test group. Conclusion : From the above results, we were able to identify that Simvastatin inhibited osteogenesis without effecting survival or cell number of osteoblasts.

• 대한한방내과학회지
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• 제32권2호
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• pp.170-187
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• 2011

Background : Obesity, the syndrome caused by a high fat diet, is a disease. At the same time, obesity causes diabetes mellitus, hyperlipidemia, and cardiovascular disease. Recently, its prevalence rate is increasing. Yagwan-cheunghyeoltang (YCT) used in this experiment is the prescription of Yagwanmoon added to Cheunghyeol-tang which is reported to be very effective in weight loss controlling and serum cholesterol. It is also reported that Yagwanmoon has significant antioxidant effects and YCT has a significant effect on blood glucose control. Objectives : This study was conducted to experimentally evaluate the effects of YCT on obesity in rats induced by high fat diet. Methods : The experiment was conducted with 4-week-old male rat s divided into 5 groups. They were a normal diet group, a high fat diet group, a positive drug control group, a 1% YCT group, and a YCT 3% group, and were tested for eight weeks. After four weeks of inducing obesity by a high fat diet, rats were allowed to lose weight by following the normal diet group, approximately 30% compared with 10 rats in each group were determined as still obese. Changes in body weight and organ weight and serum cholesterol, triglyceride, glucose-density, low density lipoprotein cholesterol, antioxidant activity were checked. Results : In the experimental groups, we observed weight loss and visceral fat reduction, improvement of liver function, reduction of serum glucose, activation of HMG-CoA reductase inhibitor, reduction of concentrations of leptin and it showed a significant effect on antioxidants and lipid peroxidation. Conclusions : YCT has significant effects on the regulation of hyperlipidemia and lipid peroxidation associated with obesity and has significant effects on, antioxidants and lipid peroxidation, too. Additional clinical studies are needed.

• 한국임상약학회지
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• 제31권4호
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• pp.278-284
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• 2021

Background: Osteoporosis is a disease that affects the quality of life and imposes a high socioeconomic burden. Studies have reported that statins, a HMG CoA reductase inhibitor, have a positive or negative effect on osteoporosis. The purpose of this study was to analyze the correlation between statins and osteoporosis risk. Methods: We used the total patient sample data of the Health Insurance Review and Assessment Service (HIRA-NPS-2018). We analyzed the prevalence of osteoporosis in adult patients of Korea who were diagnosed with dyslipidemia and were prescribed statins at the same time. The odds ratio (OR) according to the intensity and type of statin was used to confirming the prevalence. Results: Among the 1,138,899 patients included in the study, 143,895 patients used statins and 27,524 patients (19.13%) were diagnosed with osteoporosis in the statin group. The OR value of statin group was 0.96 (95% CI 0.94-0.98), confirming that the prevalence of osteoporosis decreased, and a significant decrease was seen in all statin intensity. Some of the moderate-intensity statins rather increased the prevalence of osteoporosis, but atorvastatin and rosuvastatin obtained positive results at both medium- and high-intensity doses, and lovastatin, a low-intensity statin, showed the greatest reduction in the prevalence of osteoporosis. Conclusion: We found that the prevalence of osteoporosis was reduced in the statin group, and there was a constant correlation regardless of gender or age. However, a large, prospective, double-blind and randomized study is needed for a long period of time to demonstrate the effectiveness of statins.

• 약학회지
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• 제42권5호
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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.

• 약학회지
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• 제57권1호
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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.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.531-538
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• 2015

Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusionevoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-$1{\beta}$ in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-${\kappa}B$, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of $I{\kappa}B$. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.

• Nutrition Research and Practice
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• 제2권4호
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• pp.211-217
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• 2008

This study was purposed to investigate the effect of onion or beet on plasma and liver lipids, erythrocyte Na efflux channels and platelet aggregation in simvastatin (SIM) treated hypercholesterolemic rats. Forty Sprague Dawley rats were divided into four groups and fed 0.5% cholesterol based diets containing 2 mg/kg BW simvastatin or simvastatin with 5% onion or beet powder. Plasma total cholesterol was significantly increased in SIM group compared with the control (p<0.01), and the elevated plasma total cholesterol of SIM group was significantly decreased in SIM-onion and SIM-beet groups (p<0.05). HDL-cholesterol in SIM-beet group was significantly increased compared with other groups (p<0.05). Platelet aggregation in both the maximum and initial slope was significantly decreased in SIM group compared with SIM-onion group (p<0.05). Na-K ATPase was significantly decreased in SIM group compared with the control, SIM-onion and SIM-beet groups (p<0.05). Na passive leak was significantly increased in all groups treated with SIM compared with the control (p<0.05). The total Na efflux was decreased in SIM group and increased in SIM-onion group and the difference between these two groups was significant (p<0.05). There was no difference in intracellular Na among groups. In present study, simvastatin, a HMG CoA reductase inhibitor at dose of 2mg/kg BW/day rather increased plasma total cholesterol in rats, inferring that the action mechanism of simvastatin on cholesterol metabolism differ between rat and human. Onion and beet play favorable roles in cardiovascular system by restoring the reduced Na efflux through Na-K ATPase and Na-K cotransport in SIM treated rats.