• 한국약용작물학회지
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• 제21권6호
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• pp.474-485
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• 2013

Pharmacological studies and clinical practices have indicated that Radix Astragali, a dried root of Astragalus membranaceus possesses a lot of biological activities, including antioxidant, hepatoprotective, anti-diabetic, tonic, diuretic, antimicrobial, antiviral, and immunological activities. These biological activities approved by the modern pharmacological studies are mainly due to the constituents of Astragalus membranaceus including polysaccharides, saponins, flavonoids, amino acids, and trace elements. In resent, the main constituents in the root part showing a lot of biological activities has been isolated also from the aboveground parts such as leaves and sprouts in our laboratory. However, the safety evaluation for the aboveground parts of Astragalus membranaceus should be checked before expanding their application as one of food. In the study, a 90-day rat oral gavage study has been conducted with the extracts from Astragalus membranaceus-above-ground parts at doses of 1000, 3000, and 5000mg/kg/day. The following endpoints were evaluated: clinical observations, body weight, gross and microscopic pathology, clinical chemistry, and hematology. Based on the analysis of these endpoints, it was estimated that NOEL (no observed effect level) for male rats and NOAEL (no observed adverse effect level) for female rats are 5000mg/kg/day of the water-extracts from Astragalus membranaceus-aboveground parts.

• 대한한의학방제학회지
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• 제24권3호
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• pp.163-174
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• 2016

Objectives : Rheum undulatum Linne and Glycyrriza uralensis Fischer are widely used herbal medicine. In this study, anti-oxidant and liver protective effects of R. undunlatum extract (RUE) and G. uralensis extract (GUE) were investigated in HepG2 cells, respectively. Oxidative stress and liver fibrosis were induced by arachidonic acid (AA) and iron, and CCl₄.Methods : MTT assay was assessed for cell viability, and immunoblotting analysis was performed to detect expression of apoptosis related proteins. In addition, reactive oxygen species (ROS) and mitochondrial dysfunction were measured. In vivo, BALB/c mouse were orally administrated with the aqueous extract of 10 mg/kg RUE and 100 mg/kg GUE for 3 days and then, injected with CCl₄ 0.5 ml/kg body weight to induce acute liver damage. Serum ALT level was measured, and histological change was observed in Harris's hematoxylin and eosin stainResults : RUE and GUE pre-treatment increased relative cell viability in concentration dependent manner and altered the expression levels of apoptosis-related proteins such as procaspase 3, PARP and Bcl-xL. RUE and GUE also inhibited the mitochondrial dysfunction and excessive reactive oxygen species (ROS) production induced by AA and iron. In addition, RUE and GUE activated liver kinase B1 (LKB1), by increasing phosphorylation. Moreover, RUE and GUE treatment decreased liver injuries induced by CCl₄, as evidenced by decreases in histological liver damage as well as serum alanine amino transferase (ALT) level.Conclusions : These data suggest that RUE and GUE has anti-oxidant and liver protective effects against AA and iron-induced oxidative stress and CCl₄-induced liver injury.

• 약학회지
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• 제46권2호
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• pp.129-136
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• 2002

The pathogenesis of cholestatic liver injury as well as the modulation of hepatic fibrogenesis is causally associated with involvement of reactive oxygen species (ROS) and free radical reactions. In this study, we investigated whether dried extracts of oriental medicine (LH) have antioxidant and antifibrotic effect under the biliary liver fibrosis (cirrhosis) c ondition. The female Sprague-Dawley rats were divided in six groups (Normal, N-LH, op-2, op-4, opLH-2, opLH-4) and were observed in 2 weeks or 4 weeks. For this purpose the rats were operated by bile duct ligation/scission (BDL/S), which induced to liver fibrosis and cirrhosis. After surgery, the prepared LH was administered p.o. 2 mι/day/rat in 2 weeks or 4 weeks for opLH groups. During the observation period, jaundices appeared in eyes, ears and tail of all BDL/S operated rats. And at the time of sacrifice, cholestasis was observed in proximal bile duct, especially the color of bile juice and urine in opLH-4 group showed more clear than op-2, op-4 and opLH-2 group. The value of clinical parameters and product of lipid peroxidation (MDA) in sera and the hydroxyproline (hyp) content in liver tissue were significantly increased in all liver fibrosis (cirrhosis) developed rats (p＜0.001~0.05). Among the clinical parameters of sera, value of BUN, ALP in opLH-4 group showed significantly lower than in op-4 group (p＜0.05, p＜0.001). The content of hyp in opLH-2, opLH-4 group (478.0 $\pm$ 134.3 $\mu\textrm{g}$/g 897.5 $\pm$ 118.2 $\mu\textrm{g}$/g) showed lower than in op-2, op-4 group (528.9 $\pm$ 220.7 $\mu\textrm{g}$/g, 1023.8 $\pm$ 277.1 $\mu\textrm{g}$/g) and then the value of MDA in opLH-4 was also significantly reduced to 59.4% of that in op-4 group (p＜0.001). The histological change (bile duct proliferation, fibrosis, collagen bundle) was similarly observed in op-2 group and in opLH-2 group, but the weak fibrosis and bile duct proliferation were observed in opLH-4 group compared with in op-4 group. Our data indicate that the 4 weeks treatment with LH extract suppressed lipid peroxidation and inhibited fibrotic (cirrhosis) process, and experimental cholestatic liver disease is associated with increased lipid peroxidation in BDL/S operated rats. Hence we concluded that the measurement of MDA and hyp can be useful monitor for the screening of antioxidant and antifibrotic effect in experimental liver fibrosis (cirrhosis), and LH has been shown to have hepatoprotective effect, antifibrotic effect and antioxidant effect.

• 한국식품영양과학회지
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• 제39권3호
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• pp.350-355
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• 2010

아세트아니모펜(APAP)으로 유도된 간독성 모델에 미치는 theanine의 간 보호 작용에 대하여 간 기능 지표효소의 활성 측정, 항산화 및 GSH량 측정, 조직학적 변화 등을 통해 확인하였다. Theanine은 그 자체로 항산화 효과를 보였으며, 과량 투여된 APAP에 의해 발생하는 간조직의 지질과산화의 감소와 GSH가 회복되는 것을 동물실험을 통해 확인할 수 있었다. 또한 지질과산화와 GSH의 감소로 인해 발생한 간세포의 손상이 theanine의 처리 농도에 비례하여 감소하는 것을 간수치 검사와 간조직 검사를 통해 최종 확인하였다. 지금까지 간보호에 효과를 보이는 녹차의 카테킨이 주로 연구되어 왔으나, 본 연구를 통해 녹차의 theanine도 간 보호작용을 알 수 있었다. 이러한 연구 결과는 주 아미노산 성분인 theanine을 강화시킨 기능성 녹차 및 건강기능식품 개발의 기초 자료로 활용 가능할 것으로 사료된다.

• Preventive Nutrition and Food Science
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• 제12권1호
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• pp.16-22
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• 2007

In order to evaluate the hepatoprotective effect of an herb distillate, ie., a mixture of 28 traditional Korean herbs, germanium, tormarine and Gijangsoo (Gijang water), $CCl_4$ was intraperitoneally administered to rats before or after supplementation of the diluted herb distillate (HD) for 2 weeks. Then hepatic xanthine oxidase activity and serum lipid profiles were determined. The experimental groups had higher feed intake than the normal control (NC), but had lower weight gain. Water intake and the amount of feces were not significantly different, but urine was excreted in lower amounts in all the experimental groups compared to the NC. Liver weights in the HD-supplemented groups were lower than that of the distilled water-supplemented groups (DW-groups) after $CCl_4$-administration. Serum ALT activities in all the experimental groups were higher than that of the NC-group. However, the increasing activity of serum ALT in the HD-supplemented groups (HD-groups) was lower than that of the DW-groups. Total serum and LDL-cholesterol levels were higher in all the $CCl_4$-administered groups than in the NC-groups, and serum HDL-cholesterol levels were lower in all the experimental groups compared with the NC-groups. Meanwhile, the increasing rate of total serum and LDL-cholesterol levels and the decreasing rate of HDL-cholesterol in the HD-groups were lower than that of the DW-groups. But, levels of serum TG were similar among all the experimental groups. The activities of hepatic xanthine oxidase (XOD) type O of the $CCl_4$-administered rats showed a significant increase in and an increasing rate of XOD in the HD-groups, which was lower than that of the DW-groups. On the other hand, GST activities in all the experimental groups were significantly decreased, and the decreasing rate was lower in the HD-groups than in the DW-groups. The hepatic contents of GSH and LPO in all the rats were not changed by $CCl_4$ administration. These results suggest that the decreased liver damage in the HD-supplemented groups was due to the inhibition of XOD-type O activity by constituents of HD, as well as by a prevention/inhibition of serum lipid profile changes in $CCl_4$-treated rats. However, further detailed studies are needed to support this hypothesis.

• 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.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제40권
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• pp.44.1-44.17
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• 2018

Background: Coffee extract has been investigated by many authors, and many minor components of coffee are known, such as polyphenols, diterpenes (kahweol and cafestol), melanoidins, and trigonelline, to have anti-inflammatory, anti-oxidant, anti-angiogenic, anticancer, chemoprotective, and hepatoprotective effects. Therefore, it is necessary to know its pharmacological effect on hepatocytes which show the most active cellular regeneration in body. Methods: In order to determine whether coffee extract has a beneficial effect on the liver, 20 C57BL/6J mice were intraperitoneally injected once with dialyzed coffee extract (DCE)-2.5 (equivalent to 2.5 cups of coffee a day in man), DCE-5, or DCE-10, or normal saline (control), and then followed by histological observation and IP-HPLC (immunoprecipitation high performance liquid chromatography) over 24 h. Results: Mice treated with DCE-2.5 or DCE-5 showed markedly hypertrophic hepatocytes with eosinophilic cytoplasms, while those treated with DCE-10 showed slightly hypertrophic hepatocytes, which were well aligned in hepatic cords with increased sinusoidal spaces. DCE induced the upregulations of cellular proliferation, growth factor/RAS signaling, cellular protection, p53-mediated apoptosis, angiogenesis, and antioxidant and protection-related proteins, and the downregulations of NFkB signaling proteins, inflammatory proteins, and oncogenic proteins in mouse livers. These protein expression changes induced by DCE were usually limited to the range ± 10%, suggesting murine hepatocytes were safely reactive to DCE within the threshold of physiological homeostasis. DCE-2.5 and DCE-5 induced relatively mild dose-dependent changes in protein expressions for cellular regeneration and de novo angiogenesis as compared with non-treated controls, whereas DCE-10 induced fluctuations in protein expressions. Conclusion: These observations suggested that DCE-2.5 and DCE-5 were safer and more beneficial to murine hepatocytes than DCE-10. It was also found that murine hepatocytes treated with DCE showed mild p53-mediated apoptosis, followed by cellular proliferation and growth devoid of fibrosis signaling (as determined by IP-HPLC), and subsequently progressed to rapid cellular regeneration and wound healing in the absence of any inflammatory reaction based on histologic observations.

• 한국식품저장유통학회지
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• 제24권1호
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• pp.107-115
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• 2017

동물실험에서 실크단백질 산 가수분해물을 투여하고 t-BHP투여한 군의 혈액 생화학적 검사 결과 t-BHP만 투여한 군과 비교하였을 때 AST, ALT 그리고 LDH가 실크단백질 산 가수분해물의 투여 농도가 높아질수록 수치가 감소하는 것으로 나타났고 세포가 손상할 시에 증가하는 MDA를 간 조직을 대상으로 측정한 결과 실크단백질 산 가수분해물의 농도가 높아질수록 수치가 대조군과 유사한 정도로 감소하는 것으로 보아 간 손상에 관여하는 효소의 누출 억제효과가 있는 것으로 사료된다. HPLC로 간 조직에서의 GSH 측정결과 t-BHP만 투여한 군과 비교하였을 때 유의적으로 증가하였고 조직학적 검사 결과 t-BHP만 투여한 군과 비교하였을 때 실크단백질 산 가수분해물을 투여한 군이 대조군과 가까운 모습을 보이는 것으로 관찰되어 실크단백질 산 가수분해물이 산화적 스트레스로부터의 간 보호 효과가 있는 것으로 사료된다. 따라서 실크단백질 산 가수분해물의 기능적 소재로서의 이용가능성이 확대될 것으로 사료된다.

• 생명과학회지
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• 제19권7호
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• pp.934-942
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• 2009

40% 알코올을 1주간 경구투여한 후 마늘 및 한약재 복합물을 각각 0.5%와 1%(GMP-I) 및 1%씩 (GMP-II) 식이에 혼합하여 3주간 급이하였을 때, 흰쥐의 체내 지질 성분 및 간 기능에 미치는 영향을 분석하였다 in vitro상에서 마늘 추출물의 ADH 활성은 20% 알코올농도에서 시료의 첨가량이 많아질수록 유의적으로 활성이 증가하였다. ALDH 활성은 마늘 추출물 첨가 시 무첨가구보다 활성이 낮았으나, 한약재 추출물 첨가 시 40%의 알코올농도에서 시료 첨가량의 증가에 따라 유의적으로 상승되었다. 알코올 투여 흰쥐에서 혈당은 마늘과 한약재 복합물의 급이시 마늘의 급이량이 많아질수록 혈당 저하에 효과적이었다. 혈중 총 지질, 총 콜레스테롤, 중성지방 및인지질은 마늘과 한약재 복합물 급이군에서 유의적으로 감소되었으며, 마늘의 첨가량이 많아질수록 체내 지질 감소 효과가 높았다. GOT, GPT, r-GTP 및 ALP 활성은 마늘 및 한약재 복합물의 급이로 대조군에 비해 유의적으로 감소되었다. 혈중 TBARS 함량은 마늘 및 한약재 복합물 급이 시 대조군에 비해 유의적으로 감소되었다. 간조직의 총 지질, 총 콜레스테롤 및 중성지방도 마늘 및 한약재 복합물 급이시 유의적으로 감소되었으며, TBARS 함량은 마늘의 첨가량이 증가될수록 생성이 억제되었다.