B16F10 흑색종 세포의 이동과 침윤에 미치는 동의보감 "유암" 처방에 근거한 한약복합처방들의 영향

최은옥,권다혜,황보현,김민영,지선영,홍수현,박철,황혜진,최영현,Choi, Eun Ok,Kwon, Da Hye,Hwang-Bo, Hyun,Kim, Min Young,Ji, Seon Yeong,Hong, Su Hyun,Park, Cheol,Hwang, Hye-Jin,Choi, Yung Hyun 대한한의학방제학회 2018 大韓韓醫學方劑學會誌 Vol.26 No.3

Objectives : We compared the inhibitory effects of herb-combined remedies, which were recorded on "Yooam" prescription of Dongeuibogam, on cell migration and invasion, two critical cellular processes that are often deregulated during metastasis, in B16F10 melanoma cells. For this purpose, water extracts of Sipyukmiryukieum (SYMRKU), Danjacheongpitang (DJCPT), Cheongganhaeultang (CGHUT) and Jipaesan (JPS) were used. Methods : Cytotoxicity was assessed by an MTT assay. Wound healing and matrigel transwell assays were used to examine on B16F10 cell migration and invasion. The levels of mRNA and protein expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) were analyzed by RT-PCR and Western blotting. Results : Our data showed that DJCPT showed the strongest inhibitory effect among the four prescriptions in inhibiting cell motility of B16F10 melanoma cells within the concentration range that was not cytotoxic. The inhibitory potential of colony formation was higher in DJCPT and SYMRKU compared to the other two types of prescriptions, and the inhibitory effect of invasiveness is shown in order of DJCPT, SYMRKU, CGHUT and JPS. DJCPT, and SYMRKU strongly inhibited the activity and expression of MMP-2 and MMP-9, which are important mediators in cancer invasion, compared to CGHUT and JPS, and the increased expression of TIMP-1 and TIMP-2 was also more effective in these two prescriptions. In conclusion, DJCPT is expected to exhibit the most potent blocking effect on migration and invasion among four herb-combined remedies compared in B16F10 melanoma cells. Conclusion : Overall, the results of this study will be used as an important source to validate these prescriptions in animal models and to understand the mechanism of action of herbal remedies recorded in Dongeuibogam.

C2C12 근아세포의 산화적 손상에 대한 고삼, 감초 및 백선피 복합 추출물의 보호효과

최은옥,황보현,김민영,손다희,정진우,박철,홍수현,김민주,이지영,신수진,최영현,Choi, Eun Ok,Hwang-Bo, Hyun,Kim, Min Young,Son, Da Hee,Jeong, Jin Woo,Park, Cheol,Hong, Su Hyun,Kim, Min Ju,Lee, Ji Young,Shin, Su Jin,Choi, Yung Hyun 대한한의학방제학회 2017 大韓韓醫學方劑學會誌 Vol.25 No.2

Objectives : Increased oxidative stress by reactive oxygen species (ROS) has been suggested as a major cause of muscle fatigue. Although several studies have demonstrated the various biological properties of Sophora flavescens Aiton, Glycyrrhiza uralensis Fischer and Dictamnus dasycarpus Turcz, but the antioxidative potentials have not been clearly demonstrated. The present study was designed to investigate the protective effects of their water and ethanol extract mixtures (medicinal herbal mixtures, MHMIXs) on hydrogen peroxide ($H_2O_2$)-induced cell damage and apoptosis in C2C12 myoblasts. Methods : Cytotoxicity was assessed by an MTT assay. Quantitative evaluation of apoptosis induction and ROS production was evaluated by flow cytometry analysis. Expression levels of apoptosis regulatory and DNA-damage proteins were detected by Western blotting. Result : The inhibition of $H_2O_2$-induced cell proliferation was effectively blocked in extracts of 3: 1: 1 (EMHMIXs-1) or 2: 2: 1 (EMHMIXs-2) of S. flavescens, G. uralensis and D. dasycarpus Turcz, ethanol extracts from various complex extracts in C2C12 myoblasts. EMHMIXs-1 and EMHMIXs-2 also effectively attenuated $H_2O_2$-induced C2C12 cell apoptosis, which was associated with the restoration of the upregulation of Bad and death receptor 4, and downregulation of XIAP and cIAP-1 induced by $H_2O_2$. In addition, these herbal mixtures significantly blocked the $H_2O_2$-induced ROS generation and phosphorylation of $p-{\gamma}H2A.X$, which suggests that they can prevent $H_2O_2$-induced cellular DNA damage. Conclusions : The results suggest that EMHMIXs-1 and EMHMIXs-2 could block the DAN damage and apoptosis of C2C12 myoblasts by oxidative stress through blocking ROS generation.

유암 처방에 사용되어온 한약재 복합 처방전의 항산화 및 항균활성에 관한 연구

최은옥(Eun-Ok Choi),손다희(Da Hee Son),김민영(Min Young Kim),황보현(Hyun Hwang-Bo),김홍재(Hong Jae Kim),정진우(Jin-Woo Jeong),홍수현(Su Hyun Hong),박철(Cheol Park),최영현(Yung Hyun Choi) 한국생명과학회 2016 생명과학회지 Vol.26 No.6

본 연구에서 동의보감에 기록된 유암 치료에 사용되어온 5가지 한약재 처방전인 십육미류기음, 단자청피탕, 지패산 Ⅰ, 지패산 Ⅱ와 청간해울탕의 열수와 에탄올 추출물에 대한 총 페놀 함량의 비교 분석과 항산화능 및 항균활성능을 비교 조사하였다. 열수와 70% 에탄올 추출물의 수율은 각각 지패산 Ⅱ와 단자청피탕이 가장 높았으며, 총 페놀 함량은 다른 한약재에 비해 단자청피탕이 가장 높았다. 열수 추출물의 총 페놀 함량은 지패산 Ⅰ < 청간해울탕 < 지패산 Ⅱ < 십육미류기음 < 단자청피탕 순으로 높게 나타났다. 70% 에탄올 추출물의 총 페놀 함량은 지패산 Ⅱ < 지패산 Ⅰ < 청간해울탕 < 십육미류기음 < 단자청피탕 순으로 풍부하였다. 그 중 단자청피탕과 십육미류기음의 환원력과 DPPH radical과 ABTS radical 소거능이 가장 뛰어났으며, 이들 시료의 총 페놀 함량과 그들의 항산화능과의 밀접한 상관도가 관찰되었다. 또한 Staphylococcus aureus 및 Escherichia coli에 대한 항균활성은 열수보다 70% 에탄올 추출물에서 효과가 높게 관찰되었다. 결론적으로 유암의 치료에 사용되었던 조사 대상 한약재 처방전은 항산화와 항균 활성은 그들의 총 페놀 함유량과 연관성이 높았으며, 본 연구의 결과는 각 처방전에 대한 구체적인 생리활성 비교를 위한 자료로서 활용될 것이다. Sipyukmiryuki-eum (SYMYKE), Danjacheongpi-tang (DJCPT), Jipae-san Ⅰ (JPS Ⅰ), Jipae-san Ⅱ (JPS Ⅱ), and Chungganhaeul-tang (CGHUT) are representative herb-combined remedies used in traditional Korean medicine for treating breast cancer patients, as mentioned in "Dongeuibogam." In this study, we investigated the total phenolic contents (TPCs) and the anti-oxidant and anti-microbial activities of hot water and 70% ethanol extracts of these herbal prescriptions. Among the five herb-combined remedies, the extraction yields of the hot water extracts and 70% ethanol extracts were the highest in JPS Ⅱ (34.30%) and DJCPT (30.50%), respectively. The TPCs of the hot water extracts from the herb medicines were rich in the order of JPS Ⅰ < CGHUT < JPS Ⅱ < SYMYKE < DJCPT. In addition, the 70% ethanol extracts from the herb medicines were rich in the order of JPS Ⅱ < JPS Ⅰ < CGHUT < SYMYKE < DJCPT. Among them, DJCPT and SYMYKE displayed a strong anti-oxidant capability, which was determined using ferric-reducing anti-oxidant power and scavenging of 2,2"-diphenyl-1-picrylhydrazyl and 2,2"-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical activity assays. In addition, anti-microbial activities against Staphylococcus aureus and Escherichia coli were stronger in the 70% ethanol extracts than in the hot water extracts. Together, these findings reveal a positive relationship between TPCs and their anti-oxidant activities.

초등학생의 김치 인식이 호의적 태도와 섭취에 미치는 영향

최은옥(Eun-Ok Choi),이창현(Chang-Hyeon Lee) 한국콘텐츠학회 2021 한국콘텐츠학회논문지 Vol.21 No.7

본 연구는 초등학생의 김치에 대한 인식이 태도와 섭취 빈도 및 섭취량에 미치는 영향 관계를 살펴보았다. 김치에 대한 인식은 선행연구를 참고하여 ‘우수성’, ‘정체성’, ‘세계화’ 인식으로 구성하였고, 각 인식별로 김치에 대한 선호와 비선호를 나타내는 ‘태도’와의 영향 관계와 ‘태도’가 김치 섭취에 미치는 영향을 확인하였다. 그 결과 김치의 ‘정체성’과 ‘세계화’ 인식은 ‘호의적 태도’에 정(+)의 영향을 준다는 것을 확인하였다. ‘우수성’ 인식은 ‘호의적 태도’에 유의적 영향이 나타나지 않았으나 ‘호의적 태도’에 유의한 영향을 주는 ‘정체성’과 ‘세계화’ 인식에 정(+)의 영향을 미친다는 것을 확인하였다. 김치에 대한 ‘호의적 태도’는 ‘김치 섭취 빈도’와 ‘김치섭취량’에 정(+)의 영향을 준다는 것도 확인하였다. 이러한 연구 결과를 토대로 아동의 김치 섭취 증진을 위해서는 김치의 정체성과 세계화 인식을 자극하는 교육 콘텐츠 개발과 보급의 필요성을 확인하였다. 또 그 기본이 되는 내용은 김치의 우수성인 것으로 사료된다. In this study we examined the relationships between an elementary schoolchild cognition, attitude, and the frequency and amount of kimchi consumed. Referring to previous studies, we define cognition as being composed of benefit, identity, and globalization. We examined how each cognition affected attitude, and how attitude affected amount of kimchi consumed, on a scale of preference or non-preference. We confirmed that the identity cognition and globalization cognition of kimchi have a positive effect on favorable attitude. The benefit cognition did not have a significant effect on favorable attitude, but it did have a positive effect on identity and globalization, which had a significant effect on favorable attitude. We also confirmed that favorable attitude has a positive effect on the frequency of kimchi intake and amount of kimchi intake. Given these results, it is necessary to develop and supply the educational contents that stimulate the identity and globalization of kimchi in order to improve childrens intake of kimchi, emphasizing the benefits of consuming kimchi.

ICR 마우스를 이용한 오미자, 상엽 에탄올 단독추출물 및 복합추출물의 단회경구투여 독성시험

최은옥(Eun Ok Choi),권다혜(Da Hye Kwon),김민영(Min Young Kim),황보현(Hyun Hwang-Bo),김홍재(Hong Jae Kim),안규임(Kyu Im Ahn),정진우(Jin-Woo Jeong),이기원(Ki Won Lee),김기영(Ki Young Kim),김성구(Sung Goo Kim),최영환(Young Whan Choi),홍수 한국생명과학회 2016 생명과학회지 Vol.26 No.10

오미자(Schisandrae Fructus)와 상엽(Mori folium)은 한국, 중국, 일본을 포함한 아시아 지역에서 오랫동안 식품자원 및 전통 의약제로 광범위하게 사용되어 왔다. 최근 연구에 따르면 오미자와 상엽은 항균, 항염증, 항산화, 면역기능 조절 및 혈관신생억제 등과 같은 많은 효능을 가지는 것으로 알려져 있다. 그러나 오미자(SF), 상엽(MF) 에탄올 단독추출물 및 복합추출물(medicinal herber mixture, MHMIX)에 대한 독성 및 안전성에 대해서는 거의 알려져 있지 않은 실정이다. 따라서 본 연구에서는 SF, MF 및 MHMIX가 유발하는 급성독성 및 안전성을 확인하였다. 이를 위하여 ICR mice를 대상으로 SF, MF 및 MHMIX 5,000 ㎎/㎏을 최고농도로 설정하여 단회 경구 투여하였으며, 투여 후 14일 동안의 치사율, 체중 변화, 임상증상, 음수율 및 사료섭취량과 함께 부검 소견, 장기무게 변화, 혈액학 및 혈액생화학적 검사를 실시하였다. 결과에서 나타난 바와 같이 SF, MF 및 MHMIX의 투여 후 치사율, 임상증상, 체중 및 부검 소견 상의 유의적인 변화는 관찰되지 않았다. 또한 SF, MF 및 MHMIX 투여에 따른 각 장기의 무게, 혈액학적 및 혈청학적 임상 화학적 지표에도 유의적인 변화는 관찰할 수 없었다. 따라서 SF, MF 및 MHMIX는 단회 경구 투여에 따른 치사량이 5,000 ㎎/㎏ 이상일 것으로 추정되어 ICR 마우스에 대하여 급성 독성이 없는 비교적 안전한 물질이라는 것을 알 수 있었으며, 향후 천연물 소재로서의 효능 규명을 통한 활용이 기대된다. Schisandrae fructus (SF) and Mori folium (MF) have been used as traditional medicines for thousands of years in parts of Asia, including Korea, China, and Japan. Recent researches on SF and MF have documented a wide spectrum of therapeutic properties, including anti-microbial, anti-inflammatory, anti-oxidative, immunomodulatory and anti-angiogenesis effects. However, the toxicity and safety of SF and MF, and their mixture (medicinal herber mixture, MHMIX) were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of SF, MF and MHMIX. SF, MF and MHMIX were orally administered at a dose of 5,000 ㎎/㎏ in ICR mice. Animals were monitored for the mortality and changes in the body weight, clinical signs and gross observation during the 14 days after dosing, upon necropsy. We also measured parameters of organ weight, clinical chemistry, and hematology. No dead and no clinical signs were found during the experiment period after administration of a single oral dose of SF, MF and MHMIX. There were no adverse effects on clinical signs, body weight, or organ weight and no gross pathological findings in any treatment group. Therefore, LD50 value of SF, MF and MHMIX may be over 5,000 ㎎/㎏ and it may have no side toxic effect to ICR mice. The results on the single-dose toxicity of SF, MF and MHMIX indicate that it is not possible to reach oral dose levels related to death or dose levels with any harmful side effects.

당뇨병 환자의 혈당 변동에 대한 시스템다이내믹스 모델 개발

최은옥 ( Eun Ok Choi ),곽찬영 ( Chan Yeong Kwak ) 한국시스템다이내믹스학회 2008 한국시스템다이내믹스 연구 Vol.9 No.1

HaCaT 인간 피부 각질세포에서 과산화수소 유도 산화 손상에 대한 소청자 및 소총2호의 항산화및 세포보호 효능

최은옥(Eun Ok Choi),권다혜(Da Hye Kwon),황혜진(Hye-Jin Hwang),김국진(Kook Jin Kim),이동희(Dong Hee Lee),최영현(Yung Hyun Choi) 한국생명과학회 2018 생명과학회지 Vol.28 No.4

식품 원료로도 널리 애용되는 검은콩은 풍부한 천연 페놀 화합물을 함유하고 있기 때문에 기능성 소재로서의 개발에도 매우 유용한 자원이다. 본 연구에서는 3가지 검은콩 품종[소청자(SCJ), 소청2호(SC2) 및 청자2호(CJ2)]을 대상으로 TPCs과 항산화 능을 조사하였다. 그 중에서도 TPCs는 CJ2 <SCJ <SC2의 순서로 풍부하게 존재하였으며, DPPH, ABTS 및 FRAP 분석을 통하여 SCJ와 SC2가 CJ2 보다 높은 항산화능을 가지고 있음을 확인하였다. 이러한 결과를 토대로 우리는 산화적 스트레스에 대한 SCJ와 SC2의 세포보호 효과를 HaCaT 인간 각질세포를 대상으로 조사하였다. 본 연구의 결과에 의하면, SCJ와 SC2는 H₂O₂ 처리에 의한 HaCaT 세포의 생존력 감소를 현저히 억제하여 산화적 스트레스에 대한 보호 효과가 있음을 알 수 있었다. SCJ와 SC2 전처리는 또한 HaCaT 세포에서 mitochondrial dysfunction의 차단과 pro-apoptotic Bax의 발현 변화의 정상화를 통해 H₂O₂에 의하여 유도된 apoptosis를 효과적으로 억제하였으며, DNA 손상에 대한 보호 효과와 연관성이 있었다. 또한 SCJ와 SC2는 Nrf2와 연관된 TrxR1의 발현을 효과적으로 유도하였으나, 산화적 스트레스에 대한 SCJ와 SC2의 보호 효과는 TrxR 억제제에 의하여 상쇄되었다. 이러한 결과는 SCJ와 SC2가 Nrf2 신호전달 경로 활성을 통하여 산화적 스트레스와 관련된 세포 손상을 차단함으로써 세포 보호 활성을 갖는다는 것을 의미한다. 결론적으로, SCJ와 SC2는 산화스트레스로 인한 피부 질환의 치료와 예방을 위한 응용 가능성이 높음을 보여주었다. Black soybeans are used as food sources as well as for traditional medicines because they contain an abundance of natural phenolic compounds. In this study, total phenolic contents (TPCs) of Korean black seed coat soybean varieties Socheongja (SCJ), Socheong 2 (SC2) and Cheongja 2 (CJ2) as well as their antioxidant capacities were investigated. Among them, TPCs were abundantly present in the order of CJ2<SCJ<SC2, and we confirmed that SCJ and SC2 have a higher antioxidant potential than CJ2. Based on these results, we investigated the cytoprotective effects of SCJ and SC2 in H₂O₂- stimulated HaCaT human keratinocytes. Our results revealed that treatment with SCJ and SC2 prior to H₂O₂ exposure significantly increases the viability of HaCaT cells, indicating that the exposure of HaCaT cells to SCJ and SC2 conferred a protective effect against oxidative stress. SCJ and SC2 also effectively inhibited H₂O₂-induced apoptotic cell death through the blocking of mitochondrial dysfunction. SCJ and SC2 also attenuated the phosphorylation of Histone H2AX. Furthermore, they effectively induced the levels of thioredoxin reductase (TrxR) 1, a potent antioxidant enzyme, which is associated with the induction of nuclear transcription factor erythroid-2-like factor 2 (Nrf2); however, the protective effects of SCJ and SC2 were significantly reversed by Auranofin, a TrxR inhibitor. These results indicate that they have protective activity through the blocking of cellular damage related to oxidative stress via the Nrf2 signaling pathway. In conclusion, our study indicated that SCJ and SC2 might potentially serve as novel agents for the treatment and prevention of skin disorders caused by oxidative stress.

김태수의 희곡「꽃마차는 달려간다」의 극작술 분석

최은옥 ( Eun Ok Choi ) 우리어문학회 2012 우리어문연구 Vol.43 No.-

This study is mainly about analyzing the dramaturgy of Kim Tae Soo`s The Cortegy on the way. The author`s intention of the critical analysis lies in the conviction that the author`s literary property should be turned into that of the actors and the director in the course of the dramatization of the work. 1. The story and the stage are analysed. The drama is based on the story in which the hero, Sunbo, spends a special time in preparing himself for his impeding death. In a scene heavily laden with the meanings of death in which he sees his dead wife, Sunbo comes to repents and reflects his whole life. In this particular moment, the horizon of time experience is greatly expanded and filled with a meaningful temporality. 2. The character and the dialogue are analysed. It is shown that the protagonists are Sundo with his proper command of language and the rest of the characters plays a role of the chorus in a sense that they functional and complementary. In the play, Sunbo is nothing but a coffin-maker; however, he ends up making his own coffin. A hidden narrator as Sunbo`s alter ego, Donchun, plays a complementary role in completing Sunbo`s story. The language the most of the characters command in the play takes on more expressive functions rather than on indicative functions. Slangs, idioms, sexual banters, and play of words show the antipathy against the ordinary and the universal and a new desire for a new language.

신파극에 나타난 죽음 연구

최은옥 ( Eun Ok Choi ) 우리어문학회 2006 우리어문연구 Vol.26 No.-

HaCaT 인간 각질세포에서 산화적 스트레스에 대한 머루근 수용성 추출물의 세포 보호 효과

최은옥(Eun Ok Choi),권다혜(Da Hye Kwon),황보현(Hyun Hwang-Bo),정진우(Jin-Woo Jeong),남원석(Won Sok Nam),이연희(Youn Hee Lee),양혜경(Hye Kyung Yang),황혜진(Hye Jin Hwang),김병우(Byung Woo Kim),이승훈(Seung Hun Lee),최영현(Yung Hyun Ch 한국식품영양과학회 2018 한국식품영양과학회지 Vol.47 No.1

왕머루(Vitis amurensis Rupr.)의 뿌리(머루근)는 한국을 비롯한 아시아 각국에서 다양한 질환의 예방과 치료의 목적으로 오랫동안 사용되어 왔다. 비록 머루근 추출물의 항산화 효과에 대한 몇몇 보고가 있었지만, 근본적인 분자생물학적 기전 연구는 아직 완전히 이해되지 못하고 있다. 본 연구에서는 HaCaT 각질세포에서 산화적 스트레스(H₂O₂)에 대한 머루근 열수 추출물(WEVA)의 세포 보호 효과를 조사하였다. 본 연구의 결과에 의하면 WEVA는 H2O2에 의한 HaCaT 각질세포의 생존력 저하를 현저하게 억제시켜 WEVA가 산화적 스트레스에 대한 보호 효과가 있음을 보여주었다. WEVA는 또한 H₂O₂에 의한 PARP 분해와 pro-caspase-9와 -3의 발현 억제를 차단함으로써 H₂O₂에 의한 apoptosis를 효과적으로 억제시켰다. 이러한 WEVA의 apoptosis 억제 효과는 H₂O₂에 자극받은 HaCaT 세포에서 미토콘드리아 기능손상의 감소 및 pro-apoptotic Bax와 anti-apoptotic Bcl-2의 발현 변화의 차단과 관련이 있었다. 또한, WEVA는 H2O2에 의해 유도된 세포 내 ROS 축적과 DNA 손상을 억제하였고, Nrf2의 발현 증가와 관련된 강력한 항산화 효소인 HO-1과 NQO-1의 발현을 유도하였다. 이러한 결과는 WEVA가 ROS의 생성 억제 및 Nrf2 신호 전달계 활성을 통하여 각질세포를 산화적 스트레스에 의한 apoptosis 및 DNA 손상으로부터 보호하였음을 의미한다. 따라서 본 연구의 결과는 WEVA가 산화적 스트레스로 인한 피부질환의 치료 및 예방을 위한 기능성 소재로 유용성이 있음을 보여주었다. Root of Vitis amurensis Rupr., a wild-growing grape species, has been used as a traditional medicine for the treatment of various diseases in Asian countries, including Korea. Although several studies on the antioxidant effects of V. amurensis root extracts have been carried out, the underlying molecular mechanisms remain largely unresolved. In the present study, we investigated the cytoprotective efficacies of water extract of V. amurensis root (WEVA) against oxidative stress (hydrogen peroxide, H₂O₂) in HaCaT human keratinocytes. Our data show that treatment with WEVA prior to H₂O₂ exposure significantly increased HaCaT cell viability, indicating that exposure of HaCaT cells to WEVA conferred a protective effect against oxidative stress. WEVA preconditioning also effectively inhibited H₂O2₂-induced apoptotic cell death by blocking degradation of poly (ADP-ribose) polymerase and down-regulation of pro-caspases-9 and -3. The anti-apoptotic effects of WEVA were associated with attenuation of mitochondrial dysfunction and normalization of expression changes of pro-apoptotic Bax and anti-apoptotic Bcl-2 in H₂O₂-stimulated HaCaT cells. In addition, WEVA abrogated H₂O₂-induced intracellular reactive oxygen species (ROS) accumulation and phosphorylation of histone H2AX at serine 139, a widely used marker of DNA damage. Moreover, WEVA increased the levels of hemeoxygenase-1 and NAD(P)H-quinone oxidoreductase-1, potent antioxidant enzymes associated with induction of nuclear transcription factor erythroid-2-like factor 2 (Nrf2). Thus, the present study demonstrates that WEVA protects human keratinocytes against oxidative stress-induced apoptosis and DNA damage, possibly through prevention of ROS generation and activation of Nrf2 signaling. Our data indicate that WEVA may potentially serve as an agent for treatment and prevention of skin disorders caused by oxidative stress.