• Journal of the Korean Wood Science and Technology
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• 제32권1호
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• pp.17-27
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• 2004

식용 임산자원인 산채류를 기능성 식품으로 개발하고자 산마늘을 비롯한 총 13종의 에탄올 조추출물에 대한 콜레스테롤 저하활성을 검정하였다. 즉, 콜레스테롤 생합성 과정 초기에 관여하는 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMG-CoA reductase)와 후기에 관여하는 squalene synthase의 효소 활성을 조사한 결과 산마늘 잎 에탄올 추출물이 두 효소의 활성을 공히 70% 이상 저해하여 활성이 가장 우수한 것으로 나타났다. 그리고 이러한 콜레스테롤 저하활성과 관련이 있는 물질을 탐색하고자 산마늘로부터 물질 단리를 시도하여 디클로로메탄 가용부로부터 kaempferol과 quercetin을 단리하였다. 또한 유전자 레벨에서의 콜레스테롤 저하 활성을 조사하기 위해 단리물질과 분획물을 C100세포(햄스터 유래 HMG-CoA reductase 고발현 세포주)에 각각 5 ㎍/㎖과 10 ㎍/㎖로 24시간 처리하여 HMG-CoA reductase와 squalene synthase의 mRNA 발현 정도를 조사하였다. 그 결과 10 ㎍/㎖로 kaempferol과 quercetin을 처리한 경우 두 효소의 mRNA가 전혀 발현하지 않는 것으로 나타나 유전자 레벨에서의 콜레스테롤 생합성 저해 효과를 확인할 수 있었다. 이상의 결과 산마늘 잎 에탄올 추출물은 콜레스테롤 생합성에 관여하는 HMG-CoA reductase와 squalene synthase의 활성을 저해하며 이러한 활성 저해 효과는 kaempferol과 quercetin에 기인하는 것으로 사료되었다. 특히 kaempferol과 quercetin은 여러 식물의 성분으로서 이미 알려진 화합물이지만 콜레스테롤 저하활성이 있는 것으로 밝혀진 것은 이번이 처음으로 금후 이들 물질과 이들 물질을 함유하고 있는 식물 활용에 필요한 자료를 제공하였다고 사료된다.

• 한국환경성돌연변이발암원학회지
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• 제26권2호
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• pp.35-40
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• 2006

Background: Inorganic arsenic is a human carcinogen that can target the liver, but its carcinogenic mechanisms are still unknown. Inorganic arsenic induces a spectrum of tumors including hepatocellular carcinoma in mice. Methods: Pregnant C3H mice were supplied with drinking water containing 50 ppm sodium arsenite during their pregnancy. The protein expression profile in the liver of 0.5-day-old. male offsprings exposed transplacentally to sodium arsenite was analyzed using protein 2D gel electrophoresis followed by mass spectrometry (MALDI-TOF). Results: Expression of proteins such as hydroxymethylglutaryl-CoA synthase mitochondrial precursor (HMG-CoA synthase), ${\beta}$-actin (cytoplasmic 1) and apolipoprotein A-IV precursor (Apo-AIV) were induced in mouse liver by sodium arsenite, while uricase (urate oxidase), guanine nucleotidebinding protein beta subunit 2-like 1 (RACK1) and fructose-bisphosphate aldolase B (Aldolase 2) were down-regulated. Summary: Expression of proteins that have been implicated in carcinogenesis, such as HMG-CoA, ${\beta}$-actin, and RACK1, was regulated in the liver of mice transplacentally exposed to inorganic arsenic.

• 대한유전성대사질환학회지
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• 제18권3호
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• pp.69-77
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• 2018

Pregnancy and delivery pose a high risk of developing metabolic decompensation in women with defects of ketone body metabolism. In this review, the available reported cases in pregnancy are summarized. It is very important to properly manage women with defects of ketone body metabolism during pregnancy, especially nausea and vomiting in the first trimester of pregnancy, and during labor and delivery. Pregnant women with deficiencies of HMG-CoA lyase or succinyl-CoA:3-ketoacid CoA transferase (SCOT) often experience metabolic decompensations with nausea and vomiting of pregnancy, often requiring hospitalization. For successful delivery and to reduce stresses, vaginal delivery with epidural anesthesia or elective cesarean delivery with epidural or spinal anesthesia are recommended for women with HMG-CoA lyase and SCOT deficiency. In beta-ketothiolase deficiency, four pregnancies in three patients had favorable outcomes without severe metabolic problems.

• KSBB Journal
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• 제24권2호
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• pp.163-169
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• 2009

본 연구는 Asp. terreus ATCC 20542 변이주로부터 lovastatin 생합성 유전자 중 polyketide 생합성 유전자 등을 이용한 PCR법으로 Aspergillus sp. 이외의 statin계열 물질 생산균주의 탐색법 구축 및 lovastatin 대량생산을 하고자 하였다. Lovastatin 생합성 유전자 중 가장 중요한 유전자인 polyketide synthase gene와 diketide synthase gene로부터 각각의 primer를 제작하여 PCR을 이용한 lovastatin 생산 균주를 탐색하였다. 선발된 7개의 균주의 형태학상의 특성 및 lovastatin 생산성을 검토한 결과 Aspergillus sp. 이외의 Penicillium sp.으로 추정되는 균주를 재선발하여 SJ-2로 명명하였다. 선발된 SJ-2는 액체배양 및 고체배양을 한 후 추출하여 TLC와 HPLC를 통하여 각각의 lovastatin 생산량을 비교, 검토하였다. 또한, SJ-2에 대두를 이용하여 lovastatin 고생산성을 확인한 결과, 대두-전배양체를 $30^{\circ}C$, 1시간동안 열처리하여 접종하여 본배양 15일째에 가장 높은 lovastatin을 생산할 수 있었다. In vitro assay 결과에서는 HMG-CoA reductase에 대한 저해활성도가 75%로 나타났다. 본 연구는 기존의 lovastatin 탐색법으로 널리 알려져 있는 bioassay법이 아닌 lovastatin 생합성 유전자를 이용하여 PCR을 통한 lovastatin 생산균주의 탐색이 신속하고 효과적인 방법으로 사료되었다.

• Applied Biological Chemistry
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• 제47권3호
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• pp.366-369
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• 2004

Myristica fragrans Houtt were extracted in 80% aq. MeOH and solvent fractionated sing $CHCl_3$, EtOAc, n-BuOH and water, successively. The n-BuOH fraction gave three phenylpropanoids through application of silica gel column chromatographies. The chemical structures of the phenylpropanoids were determined by the interpretation of several spectral data, including NMR and MS as meso-dihydroguaiaretic acid (1), nectandrin B (2) and syringin methyl ether (3). Compound 1, which was first isolated from this plant by authors, showed inhibitory activities with $60.0{\pm}2.1%\;(100\;{\mu}g/ml),\;42.6{\pm}0.9%\;(140\;{\mu}g/ml)\;and\;12.2{\pm}0.2%\;(200\;{\mu}g/ml)$ on ACAT(acyl-CoA:Cholesterol Acyltransferase), chitin synthase III and HMG-CoA reductase (3-hydroxy-3-methylglutaryl coenzyme A reductase), respectively. Compound 3 showed inhibitory activities with $27.2{\pm}0.9%\;(100\;{\mu}g/ml),\;45.5{\pm}0.8%\;(200\;{\mu}g/ml)$ on ACAT and chitin synthase III.

• Natural Product Sciences
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• 제20권1호
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• pp.65-70
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• 2014

This study was carried out to investigate the potential effects of Gardenia jasminoides (GJ) extracts, on hepatic steatosis and lipid metabolism in mice fed with high-fat diet (HFD). GJ extracts (100 mg/kg, ${\times}10$ weeks) fed mice showed reduced body weight, adipose tissue weight, reduced aminotransferase level in plasma and hepatic lipid (triglyceride, total cholesterol) content. These effects were accompanied by decreased expression of lipogenic genes, sterol regulatory element binding protein-1c (SREBP-1c), liver X receptor (LXR), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), cluster of differentiation 36 (CD36), lipoprotein lipase (LPL) and decreased lipogenic enzyme FAS and HMG-CoAR enzyme activities while elevating carnitine palmitoyltrasferase-1 (CPT) activity. Based on these results, we speculated that the inhibitory effect on hepatic steatosis of GJ extract containing geniposide is the result of suppression of lipid synthesis in mice fed with HFD, suggesting that GJ extract may be beneficial in preventing hepatic steatosis.

• 한국식품과학회지
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• 제47권3호
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• pp.364-372
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• 2015

이 연구는 고지방 고콜레스테롤 식이를 12주 동안 랫트에게 공급하여 복분자와 홍삼, 복분자와 홍삼 발효 추출물의 지질대사 및 비만 개선효과를 조사하였다. 정상식이, 고지방 고콜레스테롤 식이, 양성대조군, 유산균발효군, 복분자와 홍삼, 복분자와 홍삼 발효 추출물 투여군의 체중증가, 음수, 식이 섭취량은 그룹간의 유의적인 차이를 보이지 않았다. 하지만 혈중 HDL-콜레스테롤은 고지방 고콜레스테롤 식이와 비교 했을 때 복분자와 홍삼 발효 추출물에서 유의적인 증가를 보였으며, LDL-콜레스테롤, 중성지방은 유의적인 감소율을 보였다. 또한, 간 조직에서 복분자와 홍삼 발효추출물 처치에 의해 HMG-CoA reductase, LDL receptor 및 SREBP-2 mRNA의 발현 증가와 지방생성 억제를 확인하였다. 그리고 복분자와 홍삼 발효 추출물 투여군은 비만인자인 혈중 leptin과 FAS의 농도를 유의적으로 감소시켰을 뿐만 아니라 대변에서 체내 콜레스테롤 배출을 증가시켰다. 이러한 결과로 미루어 보아 복분자와 홍삼 발효 추출물은 혈중 지질 대사 및 비만의 예방에 기여할 것으로 판단된다.

• Food Science and Biotechnology
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• 제16권4호
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• pp.584-589
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• 2007

The effect of water extract of adzuki beans on acetaminophen-altered lipid metabolism was examined in rats. Control group of rats was fed a basal diet, another group of rats was fed 0.5% acetaminophen (APAP group), and a third group of rats was fed 0.5% acetaminophen plus 5% adzuki bean extract (ABE group) for 4 weeks. Serum total and HDL cholesterol levels in the APAP group were significantly lower than those in the control and ABE groups. Hepatic cholesterol $7{\alpha}-hydroxylase$ and fatty acid synthase mRNA levels in the APAP and ABE groups were significantly higher and lower than in the control group, respectively. Hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase mRNA level in the APAP group was significantly lower than in the control group, whereas that in the ABE group was significantly higher than in the APAP group. These results indicate that adzuki bean extract may improve the acetaminophen-altered serum lipid metabolism in rats.

• 약학회지
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• 제57권6호
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• pp.388-393
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• 2013

Previously, we have reported that lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, increased melanin synthesis through intracellular $Ca^{2+}$ release in B16 cells. In this study we investigated the possible involvement of nitric oxide (NO) in the mechanism of lovastatin-induced melanogenesis. Lovastatin elevated NO formation in a dose-dependent manner. Treatment with mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), precursors of cholesterol, did not significantly alter the lovastatin-induced NO production, suggesting that inhibition of cholesterol metabolism may not be involved in the mechanism of this action of lovastatin. Both NO formation and melanogenesis induced by lovastatin was significantly suppressed by treatment with $N^G$-nitro-L-arginine methyl ester (L-NAME) and 2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylinidazoline-1-oxyl-3-oxide (cPTIO), an inhibitor of NO synthase and a NO scavenger, respectively. The lovastatin-induced NO production was significantly affected not by EGTA, an extracellular $Ca^{2+}$ chelator, but by an intracellular $Ca^{2+}$ chelator (BAPTA/AM) and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8). Taken together, these results suggest that lovastatin may induce melanogenesis through NO formation mediated by intracellular $Ca^{2+}$ release in B16 cells. These results further suggest that lovastatin may be a good candidate for the therapeutic application of various hypopigmentation disorders.

• Journal of Korean Neurosurgical Society
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• 제50권5호
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• pp.403-408
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• 2011

Objective : Contrary to some clinical belief, there were quite a few studies regarding animal models of intracerebral hemorrhage (ICH) $in$ $vivo$ suggesting that prior use of statins may improve outcome after ICH. This study reports the effect of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor, simvastatin given before experimental ICH. Methods : Fifty-one rats were subjected to collagenase-induced ICH, subdivided in 3 groups according to simvastatin treatment modality, and behavioral tests were done. Hematoma volume, brain water content and hemispheric atrophy were analyzed. Immunohistochemical staining for microglia (OX-42) and endothelial nitric oxide synthase (eNOS) was performed and caspase-3 activity was also measured. Results : Pre-simvastatin therapy decreased inflammatory reaction and perihematomal cell death, but resulted in no significant reduction of brain edema and no eNOS expression in the perihematomal region. Finally, prior use of simvastatin showed less significant improvement of neurological outcome after experimental ICH when compared to post-simvastatin therapy. Conclusion : The present study suggests that statins therapy after ICH improves neurological outcome, but prior use of statins before ICH might provide only histological improvement, providing no significant impact on neurological outcome against ICH.