• 대한본초학회지
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• 제30권4호
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• pp.57-64
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• 2015

Objectives : Oxidative stress is one of the most causes of hepatocyte injury. Gleditsia spina, the thorns ofGleditsia sinensisLam., has been known for its anti-cancer and anti-inflammatory effects in Korean medicine. The present study investigated hepatoprotective effect of Gleditsia spina water extract (GSE) against oxidative stress induced by arachidonic acid (AA) + iron in HepG2 cells.Methods : To investigate cytoprotective effect of GSE, cells were pretreated with GSE and then subsequently exposed to 10 μM AA for 12 h, followed by 5 μM iron. Cell viability was monitored by MTT assay, and expression of apoptosis-related proteins was examined by immunoblot analysis. To identify responsible molecular mechanisms, reactive oxygen species (ROS) production, GSH contents, and mitochondrial membrane potential were measured. In addition, effect of GSE on nuclear factor erythroid 2-related factor 2 (Nrf2) activation was determined by immunoblot and antioxidant response element (ARE)-driven reporter gene assays.Results : GSE pretreatment prevented AA + iron-mediated cytotoxicity in concentration dependent manner. In addition, ROS production, glutathione depletion, and mitochondrial impairment by AA + iron were significantly inhibited by GSE. Furthermore, GSE promoted translocation of Nrf2 to nucleus, which acts as essential transcription factor for induction of antioxidant genes. Increased nuclear Nrf2 that caused by GSE treatment promoted transcriptional activity of ARE. Finally, GSE up-regulated sestrin-2 which was widely recognized as target gene of Nrf2.Conclusions : This study demonstrates that GSE protects hepatocytes from oxidative stress via activation of Nrf2 signaling pathway.

• 약학회지
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• 제40권6호
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• pp.727-733
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• 1996

2-(Allylthio)pyrazine is effective in selectively suppressing constitutive and inducible expression of cytochrome P450 2E1. The effect of 2-(allylthio)pyrazine against potentiat ed chemical injury was studied in rats. Vitamin-A pretreatment of rats substantially increased carbon tetrachloride hepatotoxicity, as supported by an ~4-fold increase in serum alanine aminotransferase (ALT) activity. Concomitant pretreatment of rats with 2-(allylthio)pyrazine at the daily dose of 200mg/kg resulted in a 76% decrease in vitamin-A-potentiated hepatotoxicity, which supported the possibility that 2-(allylthio)pyrazine protects the liver against chemical-induced hepatic injury by the mechanism associated with Kupffer cell inactivation. Pyridine pretreatment caused substantial enhancement in carbon tetrachloride hepatotoxicity. 2-(Allylthio)pyrazine treatment of rats reduced the pyridine-potentiated toxicity in a dose-dependent manner. Animals treated with both pyridine and 2-(allylthio)pyrazine prior to intoxicating dose of CCl$_4$ resulted in 85% and 47% decreases in pyridine-increased triglycerides and cholesterol levels in the liver. The protective effect of 2-(allylthio)pyrazine on the DNA strand breakage induced by benzenetriol was assessed by measuring the conversion of supercoiled ${\Phi}x$-174 DNA to the open relaxed form. 2-(Allylthio)pyrazine blocked the benzenetriol-induced conversion of supercoiled DNA to open circular form in a dose-dependent manner. The presence of 2-(allylthio)pyrazine at the doses from I to 10mM in the incubation mixture containing 5 ${\mu}$M benzenetriol completely protected benzenetriol-induced DNA strand breakage with the EC50 for the 2-(allylthio)pyrazine blocking being noted as ~220 ${\mu}$M, whereas allyl disulfide exerted protecting effect at relatively high concentrations (i.e. ~850 ${\mu}$M), suggesting that 2-(allylthio)pyrazine effectively scavenges the reactive oxygen species. These results provide evidence that 2-(allylthio)pyrazine blocks vitamin A- or pyridine-potentiated CCl$_4$ hepatotoxicity and that the agent is active in protecting DNA by scavenging the reactive oxygen species.

• 한국식품영양과학회지
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• 제43권6호
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• pp.791-798
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• 2014

고려엉겅퀴는 예로부터 구황식품으로 사용되어 식용뿐만 아니라 한방 약재로도 사용되어 왔으며, 최근에는 건강기능식품 원료로서도 각광받고 있다. 본 총설에서는 고려엉겅퀴에 대한 주요 생리활성을 중심으로 요약하였으며, 고려엉겅퀴의 항산화 활성, 간 보호작용, 항염증 활성 및 지표성분 pectolinarin의 다양한 생리활성도 소개하고자 기술하였다. 최근 합성 항산화제를 대체하기 위한 천연항산화제의 필요성이 점차 증가하고 있음에도 불구하고, 효능이 우수한 천연항산화제가 상업화되기 위해서는 천연항산화제에 대한 안전성 및 경제성 등이 확보되어야 할 것으로 사료된다. 고려엉겅퀴는 수천 년 동안 식품으로 사용되어 왔고, 최근에는 다양한 생리활성을 나타내는 바 건강기능식품의 원료로서 사용도가 점차 증가하고 있으며 고려엉겅퀴 추출물의 독성평가가 이루어진다면 추후 개별인정형 건강기능식품으로도 개발될 수 있을 것으로 사료된다.

• 원예과학기술지
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• 제28권4호
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• pp.685-690
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• 2010

노니($Morinda$ $citrifolia$) 부정근의 주요 성분인 rubiadin은 간 보호 효과가 있어 제약산업에서 높은 가치가 있다. 노니 부정근의 주요 유효성분인 rubiadin의 효율적인 추출조건을 규명하고자 용매 종류, 물과 메탄올의 비율(물, 20%, 40%, 60%, 80%, 100%), 추출시간 및 추출방법을 달리하여 추출하였다. 노니 부정근에서의 rubiadin의 함량분석은 HPLC 이용 분석조건을 확립하였으며, C-18 컬럼을 사용하여 280nm에서 메탄올과 물로 농도구배를 주어 분석하였다. 용매별 추출효율은 메탄올(0.08%) > 에탄올(0.05%) > 아세토니트릴(0.03%) > 아세톤(0.02%) 및 메틸렌클로라이드(0.02%) 순으로 증가하였다. 메탄올에 물의 혼합 비율을 달리하여 초음파 추출기로 1시간 동안 추출한 결과 60% 메탄올(0.21%) > 80% 메탄올(0.13%) > 100% 메탄올(0.07%) 및 40% 메탄올(0.07%) 순으로 효과적이었으며, 환류냉각 추출기로 2시간 동안 추출한 결과 60% 메탄올(0.21%) > 40% 메탄올(0.17%) > 80% 메탄올(0.14%) 용매처리구 순으로 효율이 좋았다. 추출방법 및 추출시간에 따른 rubiadin의 추출 효율을 비교하기 위해 환류냉각추출 및 초음파추출, 진탕추출법으로 추출하였다. 추출방법 및 추출시간에 따른 rubiadin의 추출효율은 초음파추출 및 진탕추출에서 각각 8 및 24시간 동안 추출했을 때 효율적이었다.

• 생명과학회지
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• 제15권3호
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• pp.461-467
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• 2005

간기능 보호 작용이 있는 것으로 알려진 DDB, selenium과 glutathione의 혼합제제인 DWP-04의 간보호 작용을 검토할 목적으로 DWP-04를 실험동물에 경구로 투여하고서 D-galactosamine으로 간독성을 유발하여 혈액의 변동 및 간 조직에서의 활성산소 생성계 및 해독계의 활성에 미치는 영향을 관찰한 결과 GaIN의 단독투여는 대조군에 비하여 혈중 간 기능 지표효소 및 간 조직에서의 지질과산화의 함량이 현저히 증가하였으나, DWP-04의 전처리로 현저히 감소되었다. CaIN의 단독 투여로 활성산소의 생성계인 phase 1계의 효소가 현저히 증가하던 것이 DWP-04의 처리로 억제되었으며 해독계인 phase II계의 효소는 GaIN의 투여로 대조군에 비하여 억제되던 것이 DWP-04의 전처리로 정상군에는 미치지 않으나 유의성 있게 증가되었다. 간 조직중 glutathine의 함량은 CaIN의 투여로 현저히 억제되었으며 DWP-04의 투여로 증가하였는데 이러한 결과는 DWP-04의 투여로 glutathione peroxidase의 활성보다는 $\gamma-glutamylcysteine$ synthetase의 활성을 조절한 결과로 생각된다. 이상의 결과를 종합하여 볼 때 DWP-04의 투여는 활성산소의 생성 및 해독계를 조절하므로서 GaIN으로 인한 간손상을 보호하는 효과가 있는 것으로 사료된다.

• 대한한의학방제학회지
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• 제19권1호
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• pp.207-217
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• 2011

Objectives : In a previous study, we have shown that Gagam-Gongjin-Dan(GGD) has an inhibitory effect on the ovalbumin-induced immune responses and a hepatoprotective effect on actaminophen-induced liver injury in Balb/c Mice. However, the possible anti-inflammatory effect of GGD extract for inflammatory mediators was not reported. Therefore, the purpose of this study was to investigate an inhibitory effects of GGD extract against lipopolysaccharides(LPS) induced inflammatory mediators in mouse peritoneal macrophages. Methods : GGD extract was prepared by extracting with methanol for 7 days. The extract was freeze-dried following filtration through vacuum distillation system. Accumulated nitrite, an oxidative product of nitric oxide(NO), was measured in the culture medium by the Griess reaction. The levels of prostaglandin $E_2(PGE_2)$, interleukin-$1{\beta}$(IL-$1{\beta}$), tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) were measured by enzyme-linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(COX-2) were measured by Western blot analysis. Results : GGD extract (50-$400\;{\mu}g$/ml) per se had no cytotoxic effect in LPS-stimulated peritoneal macrophages. GGD extract dose-dependently reduced NO, $PGE_2$, IL-$1{\beta}$ and TNF-${\alpha}$ production and COX-2 activity caused by stimulation of LPS. The levels of iNOS and COX-2 protein expressions were markedly suppressed by the treatment with GGD extract in a dose dependent manner. Conclusions : These results suggest that GGD extract has an anti-inflammatory effect against LPS-induced inflammatory mediators in peritoneal macrophages, these properties may contribute to inflammation disease care.

• 생명과학회지
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• 제23권7호
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• pp.904-912
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• 2013

눈꽃 동충하초, 번데기 동충하초, Cordycepin 고함유 번데기 동충하초 분말을 식이 중에 각각 3% 수준으로 첨가하여 4주간 흰쥐에 급여한 후, 해부하기 2일 전에 2회 사염화탄소를 복강주사하여 급성 간손상을 일으켜 임상생화학적 특성 및 조직 내 항산화 활성 및 간 조직에 미치는 영향을 검토하였다. 체중 증가량과, 식이 섭취량 및 음료섭취량은 각 실험군 모두 감소하는 경향을 보였다. 간 손상 임상 지표인 AST, ALT, LDH 활성도 각 실험군 모두 유의적으로 감소하였으나, 그 중 Cordycepin 고함유 번데기 동충하초 분말을 투여한 군에서 가장 낮은 활성을 보였다. 각 조직과 혈청의 과산화지질(TBARS)을 측정한 결과 Cordycepin 고함유 번데기 동충하초는 높은 과산화지질 억제작용을 나타내어 조직 내 항산화 물질로 잘 알려진 glutathione농도 또한 모든 조직과 혈청내에서 높은 함량을 보였다. 미네랄 함량 측정결과 지방의 산화를 촉진하는 비헴철과 항산화 성분인 아연이 정상수준까지 회복되는 경향을 보였다. 이상의 실험결과 Cordycepin 고함유 번데기 동충하초는 사염화탄소로 유발된 간 독성을 저하시키며 혈청과 간지질 대사를 개선하는 효과가 있는 것으로 사료되며 향후 간 기능 개선과 지질대사 개선효능을 가지는 건강식품 개발의 소재로 활용될 가능성이 높은 것으로 판단되어진다.

• Food Science and Biotechnology
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• 제15권1호
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• pp.122-127
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• 2006

The effects of fermented chaga mushroom (Inonotus obliquus) powder on the lipid concentrations and the activities of liver marker enzymes of serum in genetically diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats were investigated. Rats were fed a semisynthetic diet supplemented with 50 g/kg chaga mushroom powder (CM) or 50 g/kg fermented chaga mushroom powder (FCM) for 8 weeks (26 to 34 weeks of age). Nondiabetic Long-Evans Toknshima Otsuka (LETO) rats were used as age-matched nondiabetic control animals. Water consumption was significantly higher in the OLETF control than the LETO rats. Water consumption in the FCM-fed OLETF rats tended to be less than in both the OLETF control and CM-fed OLETF rats. Serum concentrations of triglycerides and total cholesterol were significantly higher in the OLETF control rats than in the LETO rats while within the OLETF rat groups, the consumption of FCM resulted in a significantly lower serum triglyceride concentration and slightly lowered serum total cholesterol concentration when compared to the OLETF control and CM-fed rats. The alanine aminotransferase (ALT) activity was significantly higher in the OLETF control than in the LETO rats, but this difference was significantly reduced compared to the CM-fed rats and essentially no difference in the ALT levels was observed between the LETO and OLETF-FCM rats. This observation suggests an adaptive effect of the fermented chaga mushroom in liver function. Livers of the LETO rats showed no histopathological changes, whereas those of the OLETF control rats were characterized by many fat depositions in the central zone of the hepatocytes. The livers of the OLETF CM-fed rats showed less fatty changes compared to the OLETF control rats and fat deposition in the hepatocytes was nearly absent. These results suggest that orally ingested fermented chaga mushroom has a potential beneficial effect on the complications known to occur in the obesity-related non-insulin dependent diabetes mellitus (NlDDM) OLETF rat.

• 한국식품영양과학회지
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• 제37권2호
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• pp.177-183
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• 2008

본 연구에서는 실험동물에 민들레 열수추출물 식이를 급여한 후, GalN으로 간손상을 유발함으로써 그 예방효과를 혈액중의 생화학적 변화 및 간조직의 효소적인 변동을 통해서 규명하고자 하였다. GalN의 투여로 현저히 증가하였던 AST, ALT의 활성은 민들레 열수추출물 투여로 억제되었으나 군간의 차이는 보이지 않았고 ALP의 활성과 TBARS 함량은 3%의 추출물을 급여한 군에서 유의적인 감소를 보였다. GalN의 투여로 현격하게 높아졌던 혈중 $TNF-{\alpha}$의 농도 또한 감소하는 경향을 확인하였으나 유의적인 차이는 보이지 않았다. GalN의 투여로 억제되었던 catalase, GSH-reductase, Mn-SOD의 활성은 민들레 추출물 투여로 유의적인 회복이 관찰되었으나 GSH-px의 활성은 그 경향만을 확인할 수 있었다. 조직 검경을 통해 민들레 열수추출물의 간염 예방효과를 확인한 결과 GalN으로 인해 유발된 광범위한 간세포의 괴사와 변성, 지방변성 등이 민들레 열수추출물식이로 다소 감소하는 것을 관찰할 수 있었다. 이상의 결과로 민들레 열수추출물은 AST, ALT와 ALP의 활성 및 산화적 스트레스를 감소시키고 활성산소 해독계에 관여하는 효소의 활성을 증가시킴으로써 GalN으로 인한 간 손상을 예방하는 것으로 사료된다.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book II
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• pp.108-109
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• 2003

Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromerol, prunol and malol, are pentacyclic triterpenoid compounds which naturally occur in a large number of vegetarian foods, medicinal herbs, and plants. They may occur in their free acid form or as aglycones for triterpenoid saponins, which are comprised of a triterpenoid aglycone, linked to one or more sugar moieties. Therefore UA and ON A are similar in pharmacological activity. Lately scientific research, which led to the identification of UA and ONA, revealed that several pharmacological effects, such as antitumor, hepatoprotective, anti-inflammatory, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. To clarify the effects of UA and ONA on skin barrier recovery, both flank skin of 8-12 weeks hairless mice were topically treated with samples (2mg/ml) after tape stripping, then measured recovery rate using TEWL on hairless mice. The recovery rate increased in UA and ONA treated groups at 6h more than 20% compared to vehicle treated group (p <0.05). For verifying the effects of UA and ONA on normal epidermal barrier, hydration and TEWL were measured for 1 and 3 weeks after UA and ONA applications (2mg/ml per day). We also investigated the features of epidermis and dermis using electron microscopy (EM) and light microscopy (LM). Both samples increased hydration compared to Vehicle group from 1 week without TEWL alteration (p<0.005). EM examination using Ru04 and OsO4 fixation revealed that secretion and numbers of lamellar bodies and complete formation of lipid bilayers were most prominent (ONA$\geq$UA>Vehicle). LM finding showed that stratum corneum was slightly increased and especially epidermal thickening and flattening was observed (UA>ONA>Vehicle). Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber increasing by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory experiments were also confirmed in vivo findings. This result suggested that the effects of UA and ONA related to not only skin barrier but also collagen and elastic fibers. Taken together, UA and ONA can be relevant candidates to improve barrier function and pertinent agents for cosmetic applications.