• 한국식품영양과학회지
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• 제46권2호
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• pp.169-176
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• 2017

본 연구에서는 쓴메밀 새싹 추출물(TBS)을 대상으로 histone acetyltransferase(HAT) 활성 저해능을 평가하고 oleic acid와 palmitic acid(OPA)를 이용하여 HepG2 세포에서 비알코올성 지방간을 유도하여 그 효과를 검토하였다. HeLa 세포의 nuclear extract(NE)를 HAT의 source로 하여 in vitro에서 TBS에 의한 HAT 활성 저해능을 평가한 결과 추출물의 처리에 의하여 HAT 활성이 억제됨을 관찰할 수 있었다. 또한, 대표적인 HAT 단백질인 p300과 CBP를 이용하여 동일한 방식으로 HAT 억제능을 평가한 결과 TBS 처리에 의하여 두 단백질 모두 활성이 감소하였으며, 특히 TBS는 p300의 활성을 특이적으로 저해함을 확인할 수 있었다. 그뿐만 아니라 HepG2 세포에 $400{\mu}M$의 oleic acid 및 $100{\mu}M$의 palmitic acid와 함께 $200{\mu}g/mL$, $500{\mu}g/mL$의 TBS를 처리한 후 NE를 이용하여 세포 내 HAT 활성을 측정한 결과 역시 추출물 처리에 의하여 세포 내 HAT 활성이 저해되어 있음이 관찰되었다. TBS에 의한 HAT 활성의 억제는 세포 내 다양한 단백질들의 아세틸화 저해와 지질축적에 의하여 아세틸화 변형을 일으키는 것으로 알려진 histone H3K9, H4K8의 아세틸화 및 H3K36의 아세틸화를 감소시켰으며, 세포 내 지질합성과 관련된 대표적 유전자인 SREBP1c, ACLY, FAS의 전사 활성 역시 저해함을 관찰하였다. 이와 같은 변화를 통하여 OPA에 의하여 HepG2 세포 내에 축적되었던 지질은 TBS의 처리에 의하여 효과적으로 감소하였으며 이때 처리된 OPA와 소재에 의한 세포 내 독성은 관찰되지 않았다. 그러므로 이러한 결과는 TBS에 의한 HAT 활성의 저해가 히스톤 단백질의 아세틸활 변형을 억제하고 이를 통하여 지방 합성 관련 유전자들의 전사 활성을 감소시켜 결과적으로 세포 내 지질축적을 방지하는 것으로 생각되며, TBS은 비알코올성 지방간질환의 예방에 좋은 천연물 소재로 활용될 수 있을 것이라 여겨진다.

• Molecular & Cellular Toxicology
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• 제4권3호
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• pp.224-229
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• 2008

Eucommia ulmoides (Duchung) is commonly used for treatment of diabetes in Korean traditional medicine. However, the exact mechanism of its anti-diabetic effect has not yet been fully elucidated. In this study, the effect of E. ulmoides extract on glucose uptake was investigated in L6 rat skeletal muscle cells. E. ulmoides extract stimulated the activity of phosphatidylinositol (PI) 3-kinase that is a major regulatory molecule in glucose uptake pathway. Protein kinase B (PKB) and protein kinase C-${\xi}$ (PKC-${\xi}$), downstream mediators of PI 3-kinase, were also activated by E. ulmoides extract. We assessed the activity of AMP-activated protein kinase (AMPK), another regulatory molecule in glucose uptake pathway. Phosphorylation level of AMPK did not change with treatment of E. ulmoides extract. Phosphorylations of p38 mitogen activated protein kinase (p38 MAPK) and acetyl-CoA carboxylase (ACC), downstream mediators of AMPK, were not significantly different. Taken together, our results suggest that E. ulmoides may stimulate glucose uptake through PI 3-kinase but not AMPK in L6 skeletal muscle cells.

• 대한한의학회지
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• 제16권2호
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• pp.320-336
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• 1995

SANGNYANGHYOLTANG(SYT) is one of the most important prescription that has been used in oriental medicine for diabetes mellitus. The sudy was done in order to elucidate the anti-diabetic effect of SYT. After pretreatment of SYT(1,000mg／kg) for 6 weeks, the effect of of SYT was prevented on serum liver function test and hepatic lipid peroxide content in rats i.v. injected with streptozotocin(STZ, 50mg／kg, tail vein) 5 weeks after pretreatment of SYT. The hepatic microsomal cytochrome P-450 and aniline hydroxylase were significantly decreased, and aminopyrine N-demethylase activity was significantly increased in SYT-STZ group as compared with control group. Changes in aldehyde oxidase, xanthine oxidase, superoxide dismutase, catalase, epoxide hydrolase, UDP-glucuronyltransferase and sulfotransferase activities were not significantly different in any of the group. The cytosolic glutathione S-transferase activity was significantly decreased in SYT-STZ group as compared with control group. The selenium-independent glutathione peroxidase was significantly increased in SYT-STZ group as compared with control group, but there was no significant difference in selenium-dependent glutathione peroxidase in any of the groups. The hepatic glutathione concentration was significantly increased in SYT-STZ group as compared with control group, and ${\gamma}-glutamylcystein$ synthetase and glutathione reductase activities were not significantly different in any of the groups. The hepatic lipid peroxide content, serum aminotransferase and sorbitol dehydrogenase activities were slightly decreased in significantly in SYT-STZ groups.

• 생약학회지
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• 제46권2호
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• pp.105-108
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• 2015

To establish the anti-diabetic(α-glucosidase inhibitory) activity of D. lotus leaf extract, isolate and identify the constituents responsible for the activity. The methanolic extract of leaves was partitioned between water, n-butanol and ethyl acetate. Bio-assay guided fractionation, based on inhibition of ;${\alpha}$-glucosidase, allowed isolation and identification of the active components. Liquid chromatography/mass spectrometry(LC/MS), ¹ H-NMR and ¹³ C-NMR spectra analyses demonstrated that the active compound was myricetin-3-O-;${\alpha}$-L-rhamnoside(1). Compound 1 demonstrated a strong inhibition on the α-glucosidase, in vitro and ;${\alpha}$-glucosidase inhibitory value was calculated as 98.08%, when that of a reference drug, acarbose was estimated as 83.03%. The present study indicates compound 1 could be considered as an ;${\alpha}$-glucosidase inhibitor and developed as an important antidiabetes agent for type II diabetes therapy.

• Journal of Microbiology and Biotechnology
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• 제25권12호
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• pp.2146-2152
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• 2015

Apios americana Medik (hereinafter Apios) has been reported to treat diseases, including cancer, hypertension, obesity, and diabetes. The therapeutic effect of Apios is likely to be associated with its anti-inflammatory activity. This study was conducted to evaluate the protective effects of Apios in animal models of acute lung injury induced by lipopolysaccharide (LPS) or pandemic H1N1 2009 influenza A virus (H1N1). Mice were exposed to LPS or H1N1 for 2-4 days to induce acute lung injury. The treatment groups were administered Apios extracts via oral injection for 8 weeks before LPS treatment or H1N1 infection. To investigate the effects of Apios, we assessed the mice for in vivo effects of Apios on immune cell infiltration and the level of pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. After induction of acute lung injury, the numbers of neutrophils and total cells were lower in the Apios-treated groups than in the non-Apios-treated LPS and H1N1 groups. The Apios groups tended to have lower levels of tumor necrosis factor-a and interleukin-6 in BAL fluid. In addition, the histopathological changes in the lungs were markedly reduced in the Apios-treated groups. These data suggest that Apios treatment reduces LPS- and H1N1-induced lung inflammation. These protective effects of Apios suggest that it may have therapeutic potential in acute lung injury.

• 생명과학회지
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• 제27권6호
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• pp.680-687
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• 2017

미생물을 이용한 천연물 발효 시 유용생리활성 증가가 보고된 바, 천년초(Opuntia humifusa; OH)를 Lactobacillus plantarum 을 이용하여 발효시켰으며(fermented Opuntia humifusa; fOH), fOH 의 비만 억제 효과를 확인하기 위해 45%Kcal 고지방식이(HFD)로 비만을 유도하였다. 이 전의 동물실험에 근거하여 OH 400 mg/kg 농도로 처리하였으며, fOH 는 최고 농도 400 mg/kg을 비롯하여 200, 100 mg/kg으로 처리하였다. 지속적인 HFD 공급으로 HFD 대조군에서는 체중, 복부지방 밀도, 난소주위 축적 지방 및 복부 축적 지방량 등이 증가하였으나, fOH 400, 200 mg/kg 처리군에서는 이들 비만인자들이 모두 유의적으로 감소하였다. fOH 100 mg/kg 처리 된 HFD 마우스는 OH 400 mg/kg 처리 마우스에 비해 의미 있는 억제 효과가 나타나지 않았다. 이는 OH에 비해 L. plantarum 로 발효된 fOH가 HFD공급 마우스에서 항비만 효과를 상승시키는 것으로 보인다. 추가적으로 2형 당뇨병 및 관련 합병증으로 확대하여 비만, 고지질혈증, 간지방증, 신장 기능 등을 이용하여 억제 기작 연구가 진행되면 대사증후군을 위한 새로운 강력한 치료제로서의 제안될 가능성이 있다.

• Journal of Acupuncture Research
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• 제23권2호
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• pp.1-19
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• 2006

Objectives : The aim of this study was to investigate the hypoglycemic and hypolipidemic activities and mechanisms of Acanthopanax senticosus (AS) herbal acupuncture. Methods : Anti-diabetic and anti-steatotic activity of the AS herbal acupuncture was investigated on C57BL/6J ob/ob mice. After random grouping at the age of 9 weeks, the herbal acupuncture groups were injected subcutaneously at the left and right Gansu (BL18) corresponding acupuncture points alternately on exactly the same time every day with 0.1ml of either 400 mg/kg or 800 mg/kg of AS (AS400 and AS800) for 8-week period. As a positive control, metformin was administrated at a dose of 300 mg/kg (MT300). Body weights were measured weekly, and on every other week blood was collected for blood glucose analysis. At the end of study, blood was also collected for determination of plasma insulin and lipid levels, after which they were killed and periepidydimal fat, liver, muscle, and pancreas were immediately removed. The removed tissues were instantly soaked in liquid nitrogen and stored at $-70^{\circ}C$ for morphological examination and mRNA analysis. Results : The AS herbal acupuncture significantly prevented weight gain on C57BL/6J ob/ob mice. The AS herbal acupuncture lowered blood glucose and improved glucose tolerance in C57BL/6J ob/ob mice. The increase of insulin response during the OGTT was inhibited by the AS herbal acupuncture. Insulin sensitivity of skeletal tissue was enhanced. Plasma lipid levels were significantly improved in the AS herbal acupuncture groups. The AS herbal acupuncture decreased hepatic lipogenesis and hepatic triglyceride production, and increased fatty acid (FA) transporter that involves in FA uptake. The AS herbal acupuncture inhibited the increase of liver mass by prevention of the accumulation of TG but did not inhibit weight gain of fat tissue on C57BL/6J ob/ob mice. Conclusion : In summary, we have demonstrated several unique properties of the AS herbal acupuncture in decreasing body weight, and reversing insulin resistance and hepatic steatosis in ob/ob mice. This AS herbal acupuncture acts as an insulin sensitizer and specifically decreases circulating glucose and lipids, and suppresses hepatic lipogenesis.

• 동의생리병리학회지
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• 제20권6호
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• pp.1530-1537
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• 2006

Platycodi Radix, the root of Platycodon grandiflorum A. DC (Campanulaceae), commonly known as Doraji in Korea (Chinese name, 'Jiegeng', and Japanese name, 'Kikyo') has been used as an expectorant in traditional Oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. In Korea, Platycodi Radix is also used as a food and employed as a folk remedy for adult diseases, such as bronchitis, asthma and pulmonary tuberculosis, hyperlipidemia, diabetes, and inflammatory diseases, and as a sedative. Several studies on its chemical and immunopharmacological effects including immunostimulation and antitumor activity have been performed. However, the relevant molecular mechanisms are poorly understood. Platycodi Radix, the root of Platycodon grandiflorum A. DC (Campanulaceae), commonly known as Doraji in Korea (Chinese name, 'Jiegeng', and Japanese name, 'Kikyo') has been used as an expectorant in traditional Oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health bensfits. In Korea, Platycodi Radix is also used as a food and employed as a folk remedy for adult diseases, such as bronchitis, asthma and pulmonary tuberculosis, hyperlipidemia, diabetes, and inflammatory diseases, and as a sedative. Several studies on its chemical and immunopharmacological effects including immunostimulation and antitumor activity have been performed. However, the relevant molecular mechanisms are poorly understood. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum AEPG) on the cell growth of human lung adenocarcinoma NCI-H460 cells in order to understand its anti-proliferative mechanism. AEPG treatment down-regulated the cyclin D1 expression in both transcriptional and translational levels without alteration of cyclin E. In AEPG-treated cells, the levels of cyclin-dependent kinase (C아) 6 mRNA and protein were significantly inhibited, but the levels of Cdk2 and Cdk4 were slightly inhibited by treatment of AEPG. AEPG treatment induced a marked accumulation of Cdk inhibitors, p16 and p27. However, AEPG treatment did not affect not only retinoblastoma protein (pRB) but also tumor suppressor p53 protein expression. The present results indicated that AEPG-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1 phase progression through induction of Cdk inhibitors such as p16 and p27, and inhibition of cyclin D1 and Cdk6. AEPG exposure, as offered by this study, provides cluse for the mechanism of AEPG action. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention and treatiment against human lung cancer.

• 생명과학회지
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• 제30권3호
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• pp.298-303
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• 2020

본 연구에서는 도깨비부채(Rodgersia podophylla)의 화장품 산업 적용 가능성을 확인하기 위해, 잎(RP-L), 줄기(RP-B), 뿌리(RP-R)의 에탄올 추출물을 조제하고 이의 항균, 항산화 및 항당뇨 활성을 평가하였다. 추출물의 총 폴리페놀 함량 분석 결과, RP-R 및 RP-L에서 382.5~387.7 mg/g의 높은 함량을 보였으며, RP-B의 경우 84.2 mg/g으로 RP-R에 비해 20% 수준을 나타내었다. 항균활성 평가에서는 RP-L 및 RP-R 추출물에서 매우 강력한 그람양성 세균에 대한 항균 활성을 확인하였으며, 특히 RP-R 추출물의 경우 제어가 어려운 그람음성의 대장균 및 P. vulgaris에 대해서도 우수한 항균활성이 확인되었다. 항산화 활성 평가 결과, 3종 부위별 추출물 모두에서 매우 강력한 DPPH 음이온 소거능, ABTS 양이온 소거능, 환원력 및 nitrite 소거능이 확인되었으며, RP-L 및 RP-R 추출물의 DPPH 음이온 및 ABTS 양이온 소거능에 대한 RC₅₀은 각각 23.0~29.7 및 15.0~18.2 ㎍/ml를 나타내어 vitamin C의 9.8 및 8.0 ㎍/ml 수준과 비교할 만 하였다. 또한 RP-R 추출물은 0.5 mg/ml 농도에서 α-glucosidase 및 β-amylase 활성을 각각 6.9% 및 48.5% 저해하여 우수한 항당뇨 활성을 나타내었다. 본 연구에서는 도깨비부채 잎 및 뿌리 추출물에서 강력한 항세균, 항산화 및 항당뇨 활성을 신규 확인하여, 향후 도깨비부채가 화장품 및 식의약품 산업에서 새로운 생물자원으로 이용 가능함을 제시하였다.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2007년도 추계 학술대회
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• pp.57-58
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• 2007

Purpose: Ginseng is a well-known medical plant used in traditional Oriental medicine. Korean red ginseng (KRG) has been known to have potent biological activities such as radical scavenging, vasodilating, anti-tumor and anti-diabetic activities. However, the mechanism of the beneficial effects of KRG on diabetes is yet to be elucidated. The present study was designed to investigate the anti-diabetic effect and mechanism of KRG extract in C57BL/KsJ db/db mice. Methods: The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. During the experiment, body weight and blood glucose levels were measured once every week. At the end of treatment, we measured Hemoglobin A1c (HbA1c), blood glucose, insulin, triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). Morphological analyses of liver, pancreas and white adipose tissue were done by histological observation through hematoxylin-eosin staining. Pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. To elucidate an action of mechanism of KRG, DNA microarray analyses were performed, and western blot and RT-PCR were conducted for validation. Results: Compared to the DC group mice, body weight gain of PIO treated group mice showed 15.2% increase, but the other group mice did not showed significant differences. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in RGL, 18.3% in RGH, 67.7% in MET, 52.3% in GPZ, 56.9% in PIO-treated group. With decreased plasma glucose levels, the insulin resistance index of the RGL-treated group was reduced by 27.7% compared to the DC group. Insulin resistance values for positive drugs were all markedly decreased by 80.8%, 41.1% and 68.9%, compared to that of DC group. HbA1c levels in RGL, RGH, MET, GPZ and PIO-treated groups were also decreased by 11.0%, 6.4%, 18.9%, 16.1% and 27.9% compared to that of DC group, and these figure revealed a similar trend shown in plasma glucose levels. Plasma TG and NEFA levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the RGL-treated group compared to those in DC group. Histological analysis of the liver of mice treated with KRG revealed a significantly decreased number of lipid droplets compared to the DC group. The control mice exhibited definitive loss and degeneration of islet, whereas mice treated with KRG preserved islet architecture. Compared to the DC group mice, KRG resulted in significant reduction of adipocytes. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin production, but decreased glucagon production. KRG treatment resulted in stimulation of AMP-activated protein kinase (AMPK) phosphorylation in the db/db mice liver. To elucidate mechanism of action of KRG extract, microarray analysis was conducted in the liver tissue of mice treated with KRG extract, and results suggest that red ginseng affects on hepatic expression of genes responsible for glycolysis, gluconeogenesis and fatty acid oxidation. In summary, multiple administration of KRG showed the hypoglycemic activity and improved glucose tolerance. In addition, KRG increased glucose utilization and improved insulin sensitivity through inhibition of lipogenesis and activation of fatty acid $\beta$-oxidation in the liver tissue. In view of our present data, we may suggest that KRG could provide a solid basis for the development of new anti-diabetic drug.