• 생명과학회지
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• 제28권7호
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• pp.765-771
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• 2018

$PPAR{\gamma}$는 지방세포의 분화를 조절하는 핵심적인 전사 인자로서 이를 조절하는 후성유전학적 조절 기전이 비만억제 연구에서 중요하게 주목 받고 있다. 선행연구에서 CACUL1이 $PPAR{\gamma}$의 전사 활성 및 지방세포의 분화를 억제하는 corepressor로서 작용함을 밝힌 바 있으며 본 연구에서는 CACUL1의 새로운 결합 단백질로 발굴된 protein arginine methyltransferase 5 (PRMT5)의 $PPAR{\gamma}$ 조절 기능을 분석하였다. PRMT5가 CACUL1과 결합함을 immunoprecipitation assay in vivo와 GST-pull down assay in vitro를 통하여 확인하였다. Luciferase reporter assay 결과로 두 단백질이 상호 협력하여 $PPAR{\gamma}$의 전사 활성을 억제함을 확인하였다. PRMT5가 안정적으로 과발현 또는 knockdown되는 3T3-L1 세포주를 제작하여 지방세포 분화에 미치는 영향을 분석한 결과, PRMT5가 3T3-L1세포의 지방세포 분화를 억제함을 증명하였다. 같은 맥락으로 PRMT5는 $PPAR{\gamma}$의 타겟 유전자인 Lpl과 aP2의 발현을 억제하는 것을 RT-qPCR로 확인하였다. 이상의 연구 결과로 PRMT5이 CACUL1과 결합하여 $PPAR{\gamma}$의 전사 활성을 방해, 나아가 지방세포의 분화를 억제하는 기존에 알려지지 않은 분자적 기전을 처음으로 밝혔다. 따라서, PRMT5 효소 활성의 조절은 비만 억제를 위한 약물 개발에 단서를 제공할 것이다.

• 생명과학회지
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• 제22권8호
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• pp.991-998
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• 2012

인삼 및 인삼 유래 물질들은 가장 대표적인 건강기능식품이며, 홍삼추출물(Panax ginseng C.A. Meyer)의 경우 항바이러스, 알레르기 감소, 항산화, 비만억제 등의 효과를 나타낸다고 알려져 있다. 대표적 건강기능식품임에도 불구하고 약물상호작용을 일으키는 대사효소(Cytochrome P450, CYP)에 대한 홍삼추출물의 영향은 보고되지 않았다. 본 연구에서는 사람의 간 마이크로좀 분획과 마우스 모델을 기반으로 홍삼엑기스의 약물대사 조절능을 평가하였다. 사람의 간 마이크로좀에서는 CYP2B6에 대한 미약한 억제 효과를 나타내었을 뿐, 타 대사효소 CYP1A2, 2B6, 2C19, 2D6와 3A에 대한 억제효과는 검출되지 않았다. 홍삼엑기스를 마우스에 50, 250, or 500 mg/kg의 농도로 3, 7, 14일간 하루 1회 경구 투여 후 간을 적출하여 대사효소의 활성 변화를 측정하였지만, 유의적인 변화는 관찰되지 않았다. 결과적으로 홍삼엑기스의 유의적인 약물대사효소에 대한 활성 조절능이 없는 것으로 판단되고, 홍삼엑기스 복용에 따른 홍삼-약물상호작용의 가능성은 없을 것으로 추정된다.

• Molecular & Cellular Toxicology
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• 제5권4호
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• pp.298-303
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• 2009

(-)-Epigallocatechin-3-gallate (EGCG), a major flavonoid in green tea has multiple health benefits including chemoprevention, anti-inflammatory, anti-diabetic, and anti-obesity effects. In connection with these effects, EGCG can be a candidate to help the treatment of metabolic diseases. Metformin is a widely used anti-diabetic drug regulating cellular energy homeostasis via AMP-activated protein kinase (AMPK) activation. Therefore, the combination of metformin with EGCG may have additive or synergistic effects on treatment of type 2 diabetes. Nevertheless, there is no report for the pharmacokinetic and/or pharmacodynamic interaction of EGCG with metformin. Here, we evaluated the pharmacokinetic and pharmacodynamic interaction between metformin and EGCG in rats. Pharmacokinetics parameters of metformin were measured after oral administration of metformin in rats pre-treated with EGCG (10 mg/kg) or saline for 7 days. The results showed that there is no significant difference in pharmacokinetic parameters between saline control and EGCG-treated group. In addition, the hepatic AMPK activation by metformin in EGCG-treated rats was also similar to the control. The lack of additive effects of EGCG on AMPK activation or intracellular uptake of metformin was also evaluated in cells in the presence or absence of EGCG. Treatment of HepG2 cells with EGCG inhibited the metformin-induced AMPK activation. Combined results suggested that EGCG has no effect on the pharmacokinetics of metformin but may contribute to metformin action.

• 약학회지
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• 제55권6호
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• pp.478-484
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• 2011

Non-alcoholic fatty liver disease is known to be frequently associated with obesity and type 2 diabetes. We examined the effects of EtOH extracts from Triticum aestivum on lipid accumulation during the differentiation of 3T3-L1 preadipocytes to screening the candidate materials in preventing non-alcoholic fatty liver disease. The lipid level in adipocytes was determined by Oil Red O staining. The treatment of 50% ethanol, but not water and 100% ethanol extracts, from Triticum aestivum at concentration of 0.5 $mg/ml$ inhibited lipid accumulation in 3T3-L1 cells, revealing no cell toxicity. Thus, the fractions of $CH_2Cl_2$, EtOAc and BuOH were separated from 50% EtOH extract to characterize anti-adipogenic effect. The $CH_2Cl_2$ fraction at concentration of $50{\mu}g/ml$ effectively inhibited the lipid accumulation in the adipocytes compared to those of EtOAc and BuOH at concentration of $50{\mu}g/ml$. The intracellular triglyceride accumulation also was significantly reduced by treatment of $CH_2Cl_2$ fraction in concentration-dependent manner. Western blot analysis showed that the $CH_2Cl_2$ fraction attenuated the intracelluar level of fatty acid synthase(FAS) accompanied by attenuated expression of Peroxidase proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) adipogenic transcription factor. These results suggest that $CH_2Cl_2$ fraction from 50% EtOH extract of Triticum aestivum may has the potent anti-adipogenic effects by inhibiting the transactivation of $PPAR{\gamma}$.

• 한국약용작물학회지
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• 제27권2호
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• pp.136-142
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• 2019

Background: Agrimonia pilosa Ledeb has been used as a traditional medicine for the treatment of hematuresis and uterine bleeding in Korea. It has been reported to have anti-obesity, anti-diabetes and anti-inflammaotry effect by regulating the inflammatory signaling pathway. However, the preventive effect of Agrimonia pilosa Ledeb on gastritis has not been elucidated. Thus, in the present study, we evaluated the effects of the water extract of Agrimonia pilosa Ledeb (APW) using HCl/EtOH-induced gastritis rat models. Method and Results: Gastritis was induced in rats by HCl/EtOH administration. The rats in each group were orally administered with two doses of APW (100 and 500 mg/kg). Omeprazole was used as a positive control drug. An enzyme-linked immunosorbent assay (ELISA) was used to measure the prostaglandin $E_2$ ($PGE_2$) levels in stomach. The treatment with 500 mg/kg APW reduced the gastric ulcer area. The APW treatment prevented a decreased in $PGE_2$ concentration induced by HCl/EtOH in rats. In the micronucleus test, the ratio of micronucleated polychromatic erythrocytes to polychromatic erythrocytes showed no significant change in the APW-treated group compared with the control group. Conclusions: These results indicate that APW could be used to prevent the gastritis caused by the HCl/EtOH-induced damage to stomach lining. In addition, the APW treatment showed no significant change in results of the micronucleus test. However, further experiments are required to determine how APW influenced the secretion of mucus and gastric acid using the chromosome aberration test and bacterial reverse mutation assay.

• 약학회지
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• 제57권6호
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• pp.420-425
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• 2013

Phentermine (PT) and phenmetrazine (PM) have been widely used as anti-obesity drugs. These drugs should be used with caution due to its close relation to amphetamine in its structure and toxicity. PT and PM, amphetamine-type anorectics, have recently been considered as alternatives for methamphetamine abuse in Korea. In addition, the misuse and abuse of PT and PM obtained by illegal sources such as the internet become a serious social problem. In the present study, a simultaneous detection and quantification method for determining PT and PM in human urine was developed and validated according to the international guidelines. The urine samples were screened using a fluorescence polarization immunooassay and analyzed by gas chromatography mass spectrometry (GC-MS) after extraction using automatic solid phase extraction (SPE) with a mixed-mode cation exchange cartridge and derivatization with pentafluoropropionic anhydride (PFPA). The validation results for selectivity, linearity, limits of detection (LOD) and quantification (LOQ), intra- and inter-assay precision and accuracy and recovery were satisfactory. The validated method was successfully applied to authentic urine samples collected from 38 drug abuse suspects. PT and/or PM were identified with or without methamphetamine in urine samples. Abuse of PT and PM have increased continuously in Korea, therefore, closer supervision of the inappropriate use of anoretics is necessary.

• 동의생리병리학회지
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• 제33권2호
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• pp.109-115
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• 2019

Aster Yomena (AY) has been used in traditional medicine to treat diseases such as obesity, hyperlipidemia, atherosclerosis, diabetes and osteoarthritis. However, protective effect of AY on acute pancreatitis (AP) has not been reported. The present study examined the anti-inflammatory effects of an ethanol extract of AY on cerulein-induced AP. AP was induced in mice by intraperitoneally injecting cerulein ($50{\mu}g/kg$) hourly for 6 times. 70% ethanol extract of AY (0.1, 0.2, and 0.5 g/kg) was orally administered for 1 week before acute pancreatitis induction. The mouse was killed at 6 hours after the final cerulein injection. The pancreas and lung were rapidly removed for histological examination and myeloperoxidase (MPO) assay. Blood samples were taken to determine serum amylase and lipase activity. In addition real-time reverse transcription-polymerase chain reaction (RT-PCR) was also performed to investigate mRNA expression of proinflammatory cytokines such as $TNF-{\alpha}$. $IL-1{\beta}$, and IL-6. Administration of AY significantly ameliorated pancreatic weight to body weight ratio, histological damages and MPO activity during AP. In addition, AY inhibited the serum amylase and lipase activity during AP. Also, mRNA expression of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 were inhibited by AY against AP. Our results revealed that pre-treatment of AY reduces the severity of cerulein-induced AP. Therefore, AY may have a protective effect drug against AP.

• 한국식품영양과학회지
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• 제45권9호
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• pp.1249-1256
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• 2016

백삼을 9회 증숙 및 건조 과정 후 제조한 흑삼의 항산화 효과급성위염 유발 모델에서 점막 보호 효과를 확인하기 위하여 증숙 횟수별 추출한 시료를 통해 실험을 진행하였다. 백삼과 흑삼의 증숙 횟수에 따른 추출물의 성분을 분석한 결과 백삼과 비교하여 흑삼 추출물에서 모두 유효성분의 양이 증가하는 것을 확인하였고, 특히 9회 반복 과정을 거친 BG군에서 가장 높은 성분 함량을 보였다. 또한, 항산화능을 확인하기 위하여 실시된 DPPH, ABTS free radical 소거 활성에서도 BG군의 억제율이 가장 높게 나타났으며, 총페놀과 총플라보노이드의 함량도 가장 높게 나타났다. 이러한 결과를 토대로 백삼과 9번 증숙 과정을 거친 흑삼을 HCl/에탄올로 유도한 급성위염 마우스에 투여한 결과 BG군에서 위 점막의 손상은 대조군과 비교하여 유의한 감소를 보였으며, 또한 백삼과 비교하여 9회 증숙한 흑삼에서 유의한 감소를 보였다. 혈액에서 측정한 활성산소종의 수치에서도 대조군과 비교하여 9회 증숙 흑삼에서 유의한 감소를 보였고, 백삼과 비교하여 뛰어난 항산화 효과를 나타내었다. 산화적 스트레스의 증가로 발생한 사이토카인의 발현을 확인한 결과에서도 COX-2, TNF-${alpha}$와 IL-6의 경우 대조군보다 유의한 감소를 보였고, 백삼과 비교하여도 유의한 감소를 보였다. 그러므로 9회 증숙한 흑삼에서는 백삼과 비교하여 유효성분 함량의 증가가 발생하여 뛰어난 항산화력을 보이고, 이에 따라 염증성 사이토카인의 발현을 억제시키므로 9회 증숙한 흑삼은 항산화 효과에 따른 급성위염 유발모델에서 점막 보호 효과가 있다고 생각한다.

• 한국식품과학회지
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• 제35권3호
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• pp.503-509
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• 2003

비만 저해 물질을 탐색하고자 전통의학에서 사용되는 200여 종류의 식용 또는 약용식물을 대상으로 지방세포 분화저해활성을 보이는 생약식물을 선별하여 용매층으로 활성이 이행되는 생약 중 황백(Phellodendri Cortex)을 최종적으로 후보식물로 선정하였다. 황백을 메탄올로 추출한 후, silica gel column chromatography, ODS RP-18 column chromatography, HPLC 등을 수행하여 지방세포 분화 저해활성을 갖는 화합물 PC-4를 분리하였다. PC-4는 노란색의 분말형태로 메탄올을 용매로 UV 최대흡수치를 조사한 결과, 222, 265, 349, 429 nm에서 최대의 UV의 흡수치를 보였으며 산이나 알카리 조건에서 최대 흡수치의 변화가 관찰되지 않았다. EI-mass spectrum을 측정한 결과, 분자량이 336.1로 예상되었으며 $^1H-NMR,\;^{13}C-NMR,\;DEPT,\;^1H-^1H\;COSY$, HMQC, HMBC NMR spectrum을 통해, PC-4는 isoquionoline alkaloide계열의 berberine으로 동정되었다. PC-4는 지방의 대사에 관여하는 중요한 효소인 fatty acid synthase와 pancreatic lipase에 대한 저해활성은 나타나지 않았으나, 지방세포 분화 저해활성은 $1\;{\mu}g/mL$의 낮은 농도에서도 관찰되었다.

• 대한본초학회지
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• 제32권5호
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• pp.57-63
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• 2017

Objectives : The aim of this study is to search Korean Medicine with the superior inhibitory effect of pancreatic lipase including a possibility as a well-matched sauce material with pork. Methods : We chose 5 samples which have the potent inhibitory effect of pancreatic lipase enzyme among 9 samples. 5 samples were Glycyrrhizae rhizoma, Cinnamomi cortex, Ganoderma lucidum, Syzygium aromaticum, and Schisandra chinensis. Animals were divided into eight groups (n=7). The experimental groups except for normal group were fed 60% high-fat diet. 5 samples were orally administered at a dose of 200 mg/kg body weight and orlistat were orally administrated at a dose of 60 mg/kg body weight for 7 days. Biochemical anaylses of 5 samples were executed based on lipid parameters such as triglyceride (TG) and total cholesterol (TC). Results : Korean Medicines with $IC_{50}$ of below $1mg/m{\ell}$ were Glycyrrhizae rhizoma, Cinnamomi cortex, Ganoderma lucidum, Syzygium aromaticum, and Schisandra chinensis. Body weight change of all drug-treated groups except Glycyrrhizae rhizoma reduced significantly during the experimental period. Orlistat treatment reduced significantly both TG and TC in serum. The significant emission of TG in fece showed in Cinnamomi cortex treatment, whereas Ganoderma lucidum and Syzygium aromaticum showed a tendency to increase without a significance. Besides, Ganoderma lucidum and Schisandra chinensis emitted significantly TC to fece. Conclusions : In conclusion, Cinnamomi cortex may exert anti-obesity effect by directly inhibiting pancreatic lipase, which would prevent the absorption of lipid from the small intestine. Accordingly, Cinnamomi cortex may suggest a high possibility as a well-matched sauce material with pork.