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      • Breeding brittle super sweet corn using tropical germplasm : 열대유전자원을 이용한 brittle 초당옥수수 신교잡종 육성

        이석기 Dongguk University 2003 국내박사

        RANK : 232223

        본 실험은 열대지역으로부터 도입된 brittle 유전자원을 이용하여 초당옥수수 신교잡종을 육성하고자 수행되었다. 2002년에 생산된 147개의 교잡종에 대하여 동국대학교 실험농장에서 포장실험을 하였으며 그 특성을 조사하였다. 1. 출웅기의 범위는 65.7일부터 79.0일까지 였으며, 출사기도 이와 비슷하였고, 출웅기와 출사기의 평균은 각각 71.8일, 72.5일 이었다. 20여 품종은 대조품종보다 빠르거나 비슷하였다. 2. 초장의 범위는 168.3cm에서 238.3cm, 착수고는 43.3cm에서 95.0 cm로 나타났으며, 초형에서는 대조품종보다 우수하거나 유사한 6개 교잡종 (67, 68, 70, 71, 72, 75)을 선발하였다. 3. 조사형질간의 상관관계분석에서는 개화기와 초장 (0.42), 착수고 (0.32)간에는 정의 상관관계를 개화기와 초형 (-0.29)간에는 부의 상관관계를 보였고, 초형과 수형 (0.43)간에는 고도의 정의 상관관계를 보였다. 4. 풋옥수수에서 가장 중요한 형질인 이삭형태와 초형의 수치를 기준으로, 대조품종인 'Cambella 90'과 유사 또는 우수한 20여 신교잡종을 선발하였다. The brittle super sweet corn germplasms, which were introduced from the tropical region, were crossed to su inbred lines to improve photoperiod sensitivity and some agronomic characters, such as flowering date, plant characters, and ear characters. After crossing, F1 was selfed to produce inbred lines adapted in temperate region by ear-to-row method until S_(5)∼S_(6) generations. In 2002, inbred lines were crossed to each other within the same flowering time and 137 brittle sweet corn hybrids were produced at the Agricultural Experimental Station of Dongguk University. The objectives of this study were both to evaluate their agronomic performance and select new superior brittle super sweet hybrids. Days to tasseling (TASS) of 88 new hybrids was between 65.0 and 79.0 days. Days to silking (SILK) was similar to days to tasseling. The means of TASS and SILK were 71.8 and 72.5 days, respectively. The plant height ranged from 168.3cm to 238.3cm and the ear height ranged from 43.3cm to 95.0cm. Since sweet corn is often consumed directly in the ear, ear traits, such as ear aspect, the number of kernel rows, row configuration (straightness and arrangement), tipfill, and ear size, are critical for fresh market. Among them, ear aspect (EA) would be the most important character to be considered during the selection for elite hybrids. Hybrid 75 showed superior EA Highly significant correlation coefficients were observed between TASS and SILK (0.57), plant height (PH: 0.42), ear height (EH: 0.32), and plant aspect (PA; -0.29). SILK was highly significantly correlated with PH (0.39). Relations between TASS, SILK and other traits were important for the selection of early-maturing hybrids. TASS and SILK showed negative correlation coefficients with PA. Based on the plant and ear aspects, 20 hybrids were selected. Among selected 20 hybrids, hybrid 2 and 101 were earlier in maturity than 'Cambella 90'. Although there were many superior hybrids, they need further evaluation for commercial use. Disease and various stress resistances and yield trial tests should be carried out under different environmental conditions.

      • A Study of the Letters of Korean Seon Master Hanam

        靑高 Dongguk University Graduate School 2003 국내석사

        RANK : 232207

        The Seon Master Hanam Sunim was one of several outstanding Seon Masters who appeared in Korea in the turbulent years that characterized the end of the Yi dynasty and the Japanese occupation of Korea. He was influential in encouraging people to develop their spirituality and attain awakening. He encouraged both Seon and Pure Land practice, and taught Sutras as well as meditation. His own life was an example of upholding the precepts and diligent spiritual practice. Despite the role he played sustaining the Seon Buddhism of Korea, there has been very little research on his life or thought in any language. Thus, the purpose of this study is to examine those aspects of Hanam Sunim's life and thought that appear in his letters. While his letters may not be able to provide a complete overview, they should be able to provide a reasonable sampling of his life and thought. Any examination of Hanam Sunim's life would be incomplete unless it examined the ending of the Yi dynasty and the Japanese occupation of Korea. For in the space of one generation, Buddhism in Korea went from being officially persecuted by the Confucian government to being permitted by the Japanese, but at the cost of being forced to serve the Japanese occupation. The Japanese installed a hierarchal organization through which they could control or at least strongly influence the activities of the temples and sunims in Korea. With this organization, they also tried to change the precepts, the Vinaya, that governed the lives of monks, by allowing people who were married, ate meat, and drank alcohol to be ordained as monks. Hanam Sunim's Dharma Teacher was the Seon Master Kyo˘ngho˘ Sunim. Kyo˘ngho˘ Sunim was perhaps single-handedly responsible for revitalizing Seon in Korea. Traveling throughout the country, he stressed the importance of awakening to one's inherent Buddha-nature. He had five main disciples who carried on his work and ensured that the seeds he had planted were to flourish in the years to come. One of these disciples was Hanam Sunim. Hanam Sunim was born to an upper-class family in 1876 and received a traditional education in the Confucian classics, but at the age of 20, he left home and became a monk. After several years, he came across a passage by the Koryo Dynasty Seon Master, Bojo Jinul, which precipitated his first enlightenment experience. The essence of that passage, "don't search for the Buddha outside of yourself," stayed with Hanam Sunim throughout his life. Hanam Sunim was famous for the diligence of his spiritual practice, and it is often said that during the last 25 years of his life he never once left his temple in the Odae Mountains. Many people, hearing of this, assume that it was because of his spiritual practice that he wouldn't leave. However, a close examination of Hanam Sunim's letters reveals that he actually did leave the Odae Mountains twice between 1926 and 1933. What kept him there in later years was his sense of responsibility for the sunims practicing in the Odae mountains, combined with his ill-health. Hanam Sunim repeatedly refused to go to Seoul, where he would have been at the bidding of the Japanese government, and it seems that people confused this as a desire to stay in the Odae Mountains. However, several times in his letters Hanam Sunim talks about moving to Tongdo Temple or to Haein Temple, both of which are in the deep mountains. It seems he just didn't want to go to Seoul. The thread that runs through all of Hanam Sunim's thought about spiritual practice is his emphasis on the need for determination and putting one's understanding into practice. Hanam Sunim taught people to practice using reflective illumination, chanting, and also hwadu's. However, regardless of the method used, Hanam Sunim said that if they practiced diligently, then they would become like a burning flame, where was no place for discriminations or delusions to stick. He also emphasized that the Buddha-dharma exists everywhere, thus there is no need to seek it anyplace else. In his letters can be seen examples of other attitudes and beliefs that Hanam Sunim held. He had great faith in the law of cause and effect and attributed whatever happened to him as the results of his own actions. He was very humble and accepted impermanence as the basic condition of the universe. Hanam Sunim probably would have criticized modern scholars for engaging in the debate about sudden enlightenment versus gradual practice and then tried to harmonize their different perspectives. However, in his letters he did include several valuable cautions about the need for continued practice even after an enlightenment experience. Rather than saying that Hanam Sunim was influenced by the thought of Bojo Jinul on this issue, it may be more accurate to say Hanam Sunim's own experiences were consistent with what Jinul had written about sudden enlightenment and gradual practice. Although Hanam Sunim was one of the foremost Seon Masters of his day, he was also known for teaching sutras to the monks during the meditation retreats. This is very unusual but Hanam Sunim felt that the proper time to study the sutras was precisely when one was practicing meditation in earnest. It was then that one would be most likely to perceive the deeper meanings of the sutras. He also viewed the sutras as useful tools to guide one's practice. In his first letter to Kyongbong Sunim, he says how careful study of the sutras can guide and prevent one from going astray in their practice. This study has been confined to only the letters of Hanam Sunim, so it has not been possible to go into depth about many of the themes that appear in Hanam Sunim's thought. However, I hope it has been sufficient to provide an overview of the major areas of his thought, and hopefully this will help entice future scholars to more closely examine Hanam Sunim and the other great Korean monks and nuns of the late 19^(th) and early 20^(th) centuries. 한암대선사는 구한말에서 한일합방이라는 한국역사의 대혼란기에 출현했던 가장 뛰어난 선사들 중의 한 사람이었다. 그는 사람들이자신들의 영성을 발전시켜 깨달음을 얻도록 하는데 큰 영향력을 미쳤다. 그는 선수행과 정토수행 두가지를 다 독려하였으며 경은 물론이고 참선도 가르쳤다. 그 자신의 삶은 계행을 몸소 실천하고 부단없이 참선을 수행하는 전형 그 자체였다. 한국의 선불교를 지탱해나가는데 그가 행한 역할의 전적에도 불과하고, 그의 삶과 사상의 궤적에 대한연구는 어느 나라의 언어로도 거의 찾아 볼 수 없는 실정이다. 따라서 본 연구의 목적은 서간문에 나타난 한암선사의 삶과 사상을 검토하는데 있다. 서간문이 선사의 삶과 사상의 전체적인 모습을 완벽하게 제공할 수는 없을지 모르지만, 적어도 상당한 부분을 담아낼 수 있으리라고 본다. 한암스님의 삶에 대한 연구는 구한말과 일제 통치기를 검토 하지 않고서는 불완전하게 된다. 왜냐하면 한 세대동안 한국불교는 유교국가에서 공적으로 박해를 받아왔던 상태에서 일본인들에 의해서는용인되는 상태로 바뀌었지만, 일본의 식민지 지배에 강제로 동참한다는 대가를 치르고서 였기 때문이다. 일본은 위계체제적인 조직을 만들어서 한국내의 사찰과 스님들의 활동을 통제하거나 강력히 규제할 수 있도록 하였다. 그 조직을 통해서 일본인들은 승려들의 삶을 지배하는 계를 바꾸려고 시도하여, 계를 받은 승려들이 혼인을 하고, 육식을 하며, 음주을 하도록 허용하였다. 한암스님의 법사 스님은 경허선사였다. 경허선사는 아마도 혼자의 힘으로 한국의 선불교를 다시 일으키신 분이라고 할 수 있을 것이다. 경허스님은 온 나라를 이곳 저곳 다니시며, 자성을 깨달음이 얼마나 중요한지를 가르치셨다. 그는 당신의 작업을 이어갈 다섯 명의 제자를 두었는데 당신이 뿌린 씨가 앞으로 올 시대에 번성하리라는 것을 확신하셨으며, 그 제자들 중의 한 사람이 바로 한암스님이시다. 한암스님은 1876년 양반집안에 태어나셨으며, 유학의 고전을 배우는 전통적인 교육을 받으셨지만, 스무살 되던 해에 출가하여 스님이 되셨다. 몇 해 뒤에 스님은 당신의 첫번째 깨달음을 촉발시키는, 고려시대의 선사인 보조 지눌대사의 말씀과 조우하게 된다. 그 말씀의 골자는 "밖에서 부처를 찾지 말라."였으며, 한암스님은 평생동안 이 말씀을 수지하셨다. 한암스님은 당신의 근면한 참선수행으로 유명하였는데, 생의 마지막 25년 동안 오대산에 있는 당신이 머무시던 절에서 한번도 나와 보신 적이 없는 것으로 알려져 있다. 이 얘기를 듣고 많은 사람들은 당신이 절을 떠나시지 않은 것은 참선 수행 때문이었을 것이라고 추측한다. 그러나, 한암스님의 서간문을 자세히 살펴보면, 스님은 1926년과 1933년 사이에 오대산을 두번 떠나신 적이 있음이 드러난다. 생의 말년에 스님이 산에 머무르셨던 이유는 오대산에 수행하고 있는 승으로서의 책임감과 악화된 건강상태 때문이었다. 한암스님은 서울로 가시기를 여러 번 거절하셨다. 서울에 가셨더라면 스님은 일본정부의 뜻대로 움직이실 수 밖에 없었기 때문이다. 이것을 사람들은 스님이 오대산에 머물기를 바라신다고 여겼던 것 같다. 그러나, 서간문의 곳곳에서 한암스님은 통도사나 해인사로 옮기시는 문제를 말씀하고 계신데, 이 두 사찰 다 깊은 산중에 있다. 스님은 그저 서울에는 가고 싶어하지 않으신 것처럼 보인다. 참선 수행에 관한 한암스님의 사상을 관통해서 흐르고 있는 맥은 수행자의 단호한 결의의 필요성과 수행자가 이해한 바를 실제로 실행에 옮기는 것을 강조하신 점이다. 한암스님은 사람들로 하여금 화두, 묵언수행, 염불을 하도록 가르치셨다. 그러나, 스님은, 방법이 무엇이건 간에 부지런히 수행만 하면 타오르는 불꽃과 같이 되어서, 분별심이나 망상이 붙을 자리가 없는 경지에 이르게 된다고 말씀하셨다. 그는 또한 불법은 어디에나 있으므로 불법을 찾기 위해 다른 장소를 찾아 다닐 필요가 없다고 강조하셨다. 서간문에서 우리는 한암스님이 가지셨던 믿음과 그 밖의 스님의 마음 가짐을 엿볼 수도 있다. 스님은 인과법을 철두철미하게 믿으셨고, 당신에게 벌어진 일은 무엇이든지 간에 당신그것을 당신이 저질렀던 행의 결과로 돌리셨다. 스님은 매우 겸허하셨고, 일시성(영원한 것이 없음)을 우주의 기본적인 조건으로 받아드리셨다. 한암스님은 아마도 돈오 점수에 관한 논쟁을 벌이는 지금의 학자들을 비판하시면서, 학자들이 지닌 각기 다른 시각들이 조화를 이루도록 노력하실지도 모른다. 그러나, 그의 서간문에는 깨달음의 경험을 한 이후에 조차도 지속적인 수행을 할 필요가 있음을 여러번 강조하여 주의를 주고 계신 것을 볼 수 있다. 이 문제에 대해서는 한암스님이 보조 지눌대사의 사상에 영향을 받았다기 보다는, 한암스님 자신의 체험이 지눌대사가 돈오와 점수에 대해 서술해 놓은 것과 일치했다고 말하는 편이 더 정확하리라고 본다. 비록 한암스님이 당대 최고의 선사중의 한 분이었다고는 하지만, 안거 기간 중에는 승려들에게 경도 가르치셨다는 사실 역시 잘 알려져 있다. 이것은 대단이 이례적인 것이지만, 한암스님은 수행자가 경을 공부해야 하는 최적의 시기는 참선 수행을 진실하게 하고 있을 때라고 느끼셨다. 그 시기야말로 수행자가 경의 깊은 뜻을 파악하기에 가장 좋은 때이기 때문이다. 그는 또한 경은 수행를 이끌어가는 매우 유용한 도구하고 보았다. 경봉스님께 보낸 첫 편지에서 한암스님은 경을 조심스레 공부하는 것이 어떻게 수행자가 제대로 수행할 수 있도록 이끌어 주며, 잘못된 수행으로 빠지지 않도록 막아주는지를 말하고 있다. 본 연구는 한암스님의 쓰신 서간문에만 한정되어 있다. 따라서 한암스님의 사상에서 나타나고 있는 여러 주제들을 보다 심도 있게 파고든다는 것은 가능하지 않았다. 그러나, 필자는 본 논문이 한암스님의 사상의 여러 영역을 개괄적으로 소개하기에는 충분하며, 이것이 앞으로 다른 학자들로 하여금 한암스님을 비롯하여 19세기 말과 20세기 초반의 한국의 다른 위대한 남녀 선사들에 대한 연구로 이어지는 촉발제가 되기를 바라마지 않는다.

      • Effects of compost and NPK fertilizer on biomass production and quality traits of moringa oleifera lam

        Muhammad Sarwar Dongguk University 2018 국내박사

        RANK : 231967

        This research was conducted to investigate the role of compost and NPK fertilizer application on vegetative growth, biochemical characteristics and antioxidant activities of Moringa oleifera hybrid PKM-1 under field and greenhouse conditions. Two independent experiments were conducted to evaluate the growth development through plant height, stem girth, number of leaves per plant, number of branches per plant, whereas quality traits and antioxidant activities by analyzing biochemical and DPPH scavenging activity, ABTS scavenging activity, Nitric oxide scavenging activity and ferric reducing antioxidant potential (FRAP). The research was done in the field and greenhouse of Dongguk University Biomedi Campus during 2016-2017. In field experiment, six treatments with control were replicated three times in a randomized complete block design (RCBD) and equal size of seedlings at the rate of 75 per plot was transplanted. The greenhouse experiment was designed with six treatments including control which were replicated three times with completely randomized design (CRD). There were 30 plants per block (i.e. 5 plants per treatment level in a block). There were 90 plants in three replications. The compost was applied one week before transplanting the seedlings and NPK was applied after one week of seedling transplanting. From the field experiment it is evident that NPK 120 kg ha-1 was the optimum dose significantly to get better biomass production along with maximum protein contents. Whereas combined application of NPK and compost (50+50%) was superior to all other treatments to produce highest carbohydrates and antioxidant activities. The highest carbohydrate contents were observed in the month of August while the highest phenolic and flavonoid contents were observed in the month of October. Enhanced antioxidant activities were observed in the month of August in terms of DPPH, ABTS, and NOX scavenging activities while FRAP activity in the month of October. In greenhouse experiment it is observed that highest vegetative growth attributes and protein contents were obtained with the application of 2 g NPK. Whereas highest carbohydrates, phenolic and flavonoid contents along with highest antioxidant activities were observed in plants treated 100 g compost. Therefore, it is concluded that NPK fertilizer alone is effective for maximum biomass production and higher protein contents of moringa whereas compost alone or combine with NPK fertilizer increased the quality traits of moringa oleifera Lam. 본 논문은 가축분퇴비와 무기질 비료의 시용이 Moringa oleifera hybrid PKM-1의 생장, 생화학적 특성 및 항산화 활성에 미치는 영향을 확인하기 위해 수행되었다. 모링가의 생장 발달은 초장, 경직경, 엽수, 가지수를 측정하여 평가하였으며, 생육 조사와 품질 특성 평가 모두 노지와 온실 조건에서 독립적으로 진행하였다. 모링가 종자는 온실에서 2주 간 발아시킨 뒤 성장한 유묘를 동국대학교 바이오메디캠퍼스 내에 위치한 노지와 온실에 이식하였으며 2016년 04월부터 2017년 10월까지 실험을 수행하였다. 노지 실험을 위해 가축분퇴비와 무기질 (NPK) 비료를 처리 별로 시용한 뒤 멀칭 후 동일한 크기의 유묘를 plot 당 75개체씩 이식하였으며, 처리 당 3 plot씩 난괴법 (RCBD)을 적용하였다. 온실에서는 block 당 30 개체 (처리 수준 당 5 개체, 6 처리)를 3 반복씩 총 90 개체를 완전임의배치법 (CRD)으로 설계하였으며, 토양은 묘목 이식 1주 전에 가축분퇴비를 시용 후, 유묘 이식 1주 뒤 NPK 비료를 처리하였다. 노지 실험에서는 NPK 120 kg ha-1 처리구에서 최대의 생장 발달을 보였고, 단백질 함량도 가장 높게 나타났다. 반면 가축분퇴비와 NPK의 50:50 혼용 처리구에서 가장 높은 탄수화물 함량과 항산화 활성이 확인되었으며, 탄수화물 함량은 8월에 수집한 처리구에서, 페놀 및 플라보노이드 함량은 10월에 수집한 처리구에서 높게 측정되었다. 항산화 활성은 DPPH, ABTS 및 NOX assay의 경우 8월, FRAP assay에서는 10월에 수집한 처리구에서 가장 높게 측정되었다. 온실 실험에서는 NPK 2g을 처리했을 때 최대 생장 발달을 보였고, 단백질 함량도 가장 높게 조사되었다. 한편, 가축분퇴비 100g 단독 처리구에서 탄수화물 함량과 페놀 및 플라보노이드 함량이 가장 높게 나타났으며, 항산화 활성도 모든 처리구 중에 가장 우수한 것으로 확인되었다. 따라서 본 연구결과, 모링가의 높은 바이오매스 생산을 위해서는 NPK 비료의 단독 시용이 효과적이며, 고품질의 모링가 재배를 위해서는 가축분퇴비 단독 또는 혼용 처리가 효과적인 것으로 판단된다.

      • Neurotrophic effects of stigmasterol in dissociated rat hippocampal cultures

        Haque, Md. Nazmul Dongguk University 2019 국내박사

        RANK : 231967

        Neurotrophic Effects of Stigmasterol in Dissociated Rat Hippocampal Cultures 흰쥐 배양해마신경세포에서 Stigmasterol의 신경성장효능 Md. Nazmul Haque Department of Anatomy Graduate School of Dongguk University College of Medicine 지도교수 : 문일수 의료서비스의 향상으로 인간의 수명이 증가되었지만 동시에 퇴행성뇌질환이 증가되어 사회적 문제가 되고 있다. 뇌신경세포의 퇴행은 신경성장인자(neurotrophic factor)의 부족이 중요 원인이며, 신경성장인자의 보급은 신경세포신생(neurogenesis) 및 신경망의 회복으로 퇴행성뇌질환을 호전시킬 수 있음이 밝혀졌다. 스테롤(sterol)은 동식물 유래의 많은 식품에 풍부히 포함되어 있으며, 식물성 스테롤은 sitosterol, campesterol, stigmasterol이 대표적이다. 이 가운데 Stigmasterol (ST)은 많은 채소류, 견과류, 콩, 씨앗 및 약초에서 발견된다. ST은 혈액-뇌 관문을 통과할 수 있고, androgens, corticoids-1, estrogens, progesterone 및 vitamin D3의 합성에 필요하다. 또한 ST은 흥분성 글루탐산 신경전달(glutamatergic neurotransmission)을 촉진하고acetylcholinesterase 활성을 억제하여 기억증진효능이 증명되었다. 본 연구에서는 ST이 신경세포의 성장과 발달에 미치는 영향을 분자 및 세포수준에서 연구하였다. 먼저 ST이 유전자표현에 미치는 영향을 조사한 75 μM 농도에서 신경돌기생성효능이 있어 축삭과 가지돌기의 성장을 촉진하였다. 전사체(transcriptomics) 분석을 통하여 24 유전자(up/down; 20/4)가 p <0.05 및 q <0.05를 통과하였고, FDR q-value cutoff <0.2를 적용할 경우, immediate early genes (IEGs), CNS 발달(neurite outgrowth 및 synaptic transmission) 유전자들이 특징적으로 영향을 받았다. CNS development Gene Ontologies (GOs)의 Venn diagram을 분석하면 Reln이 중심적 역할을 함이 들어나며, 이는 또한 Dcx, Egr1, Ntrk2, Slc24a2과 같은 'heb' 유전자와 co-expression network을 형성하였다. 다음으로, ST은 Erk1/2 및 Creb signaling과 Arp2 및 Cdc42 증가를 통하여 actin organization과 spine head 발달을 촉진하였다. 마지막으로 신경세포의 이주(neuronal migration)를in vitro neurosphere migration assay을 통하여 조사하였다. E-14 cortical neuron의 neurosphre 배양에 ST을 첨가하면, 이주신경세포의 수와 이주거리가 현저히 증가하였다. ST은 Relin과 그 아래 신호단백질 phospho-c-Jun N-terminal kinase, doublecortin 및 dynein heavy chain을 증가시켰으며,in silico molecular docking simulation 결과 Relin receptor ApoER2와 결합하는 것으로 나타났다. 결론적으로 본 연구는 ST이 세포이주, 신경돌기 발달, 글루탐산 흥분성 연접의 생성을 촉진하여 정상뇌의 발달에 기어함이 밝혀졌다. 이 결과는 또한 손상뇌의 회복에 중요한 작용을 할 것으로 예상된다. ABSTRACT Neurotrophic Effects of Stigmasterol in Dissociated Rat Hippocampal Cultures Md. Nazmul Haque Department of Anatomy Graduate School of Dongguk University College of Medicine 지도교수 : 문일수 Global improvement of life style and medical facilities increases the life expectancy of people together with the prevalence of age related neurodegenerative disorders, which is a growing concern in modern healthcare. The decreased level of neurotrophic factors is primarily responsible for the pathogenesis of neurological disorders associated with the region specific neuronal degeneration and atrophy. Although current pharmacotherapies can manage some of the disease symptoms but there is no complete cure for neurodegenerative diseases so far. Several studies have demonstrated that induction of neuritogenesis either by neurotrophic factors or drugs can ameliorate, halt or even reverse the disease symptoms through the reconstruction of partially damage neuronal network. Therefore, now a day’s research effort is being paid to explore potential neuromodulatory drug candidate for effective treatment of neurodegenerative diseases. Sterols are lipids which are abundantly present in a western type diet of animal and plant origin. Depending on the nature of the diet, most commonly available plant sterols are sitosterol (65%), campesterol (32%), and stigmasterol (3%). Among them Stigmasterol, which have high structural and functional similarity to cholesterol is found in many vegetables, nuts, legumes, seeds and herbs. It can easily cross blood brain barrier and serves as a precursor for the synthesis of androgens, corticoids-1, estrogens, progesterone and vitamin D3. Furthermore, it has stimulating effect on glutamatergic neurotransmission and inhibitory effect on acetylcholinesterase activity and also possesses enhancing ability of memory. However, it remains elusive if stigmasterol could contribute beneficial effect on the development of nervous system neuron and facilitates reconstruction of damaged neuronal cytoarchitecture and synaptic network, the major pathophysilogical feature in most of the neurodegenerative disorders. Therefore, in my doctoral study, I have paid efforts to evaluate the neurotrophic effect of stigmasterol in the development of central nervous system neurons and their molecular basis of actions using different morphometric and cell biological assays at in vitro condition. To begin with this, I have optimized the concentration of stigmasterol via the evaluation of the neuritogeneic properties using rat primary hippocampal cell as a model system. I have found stigmastrol at 75 μM concentration promotes the maximum neuritogenic activity compared to vehicle [ethanol (EtOH) final concentration <0.4% (v/v)]. At this optimal concentration ST flourished neuronal cytocrchitecture by increasing the complexity of both dendrites and axon by extending their lengths and sprouting arbors, and enhances functional synaptic plasticity by accumulating the ready to release synaptic vesicle. Then, as an approach to identify the molecular basis of promising neuronal cytoarchitectural modulation by ST, I have carried out transcriptomics study and further analysis to identify the ST induced changes in potential gene expression profiles. Total mRNA-Sequencing was performed, and I have found that of the activated genes, 24 genes (up/down; 20/4) passed the more stringent criterion of both p <0.05 and q <0.05. After applying a stringent FDR q-value cutoff of <0.2, it was found ST induced many immediate early genes (IEGs), and that a major proportion of upregulated genes were CNS development (neurite outgrowth or synaptic transmission). In a Venn diagram for CNS development Gene Ontologies (GOs) (i.e., axon development, dendrite development, modulation of synaptic transmission), Reln emerged as a central player in these processes, and highly interconnected ‘hub’ genes, including Dcx, Egr1, Ntrk2, and Slc24a2, were revealed by gene co-expression networks. Finally, transcriptomic data was confirmed by immunocytochemistry of primary hippocampal neurons. Next, I sought to investigate the potential abilities ST to modulate the synaptic plasticity towards the induction of immediate early genes (IEGs) and demonstrated that ST triggered glutametergic synapse formation by increasing the densities of pre- and post synaptic proteins and their colocalized punctae. At the molecular leve, ST activated Erk1/2 and Creb signaling and upregulated Arp2 and Cdc42, which both plays central roles in actin organization and spine head development. Furthermore, DiO ((benzoxazolium, 3-octadecyl-2- [3-(3-octadecyl-2(3H) -benzoxazolylidene)-1- propenyl]-,perchlorate/34215-57-1) staining of live neurons showed ST increased the densities of dendritic filopodia and mushroom-type mature spines. Finally, to evaluate roles of ST on neuronal migration, I have performed in vitro neurosphere migration assay of E-14 cortical neuron and found ST significantly increased not only the numbers of migratory neurons but also the distance of their movement from the centers of neurospheres as compared to vehicle cultures. ST upregulated the expressions of Relin and its downstream signaling molecules like phospho-JNK (c-Jun N-terminal kinase), doublecortin and dynein heavy chain in migratory neurons. Furthermore, computational receptor-ligand binding in silico molecular docking simulation study indicated that ST interacts with Relin receptor ApoER2 by forming a strong hydrogen bond with Lys2467 and other van der Waals interactions. Together, this study have shown that ST activates signaling pathways leading to neuronal migration, neurite development, and formation of glutamatergic excitatory synapses, which are essential process during both normal brain development and recovery of damaged brains. Therefore, this study provides cell and molecular evidence that ST be viewed as a potential neurotrophic, therapeutic and preventative agent for diverse neurodegenerative diseases.

      • Breeding of superior shrunken-2(sh2) corn inbreds using introduced germplasm

        Cha, Sung Won Dongguk University Graduate School 2001 국내석사

        RANK : 231967

        본 실험은 외국유전자원을 이용하여 국내 초당옥수수 자식계통을 육성하고자 2000년 동국대학교 실험농장에서 S4~S5세대에 3개의 tester로 톱교잡 검정교배 교잡종을 대상으로 포장실험을 실시하였다. 1. 이삭모양과 관능검사, 개화기에 대한 GCA값을 기준으로 20개의 우수 계통을 선발하였다. 2. 선발된 20개의 계통 중 5개 계통은 선발된 계통 내에서 상대적으로 조생계통이며, 5개 계통은 만생계통이었다. 3. 개화기와 이삭길이, 이삭당 열수, 열당 립수, 이삭중, 이삭모양간에는 상관관계가 나타나지 않았다. 4. 개화기와 이삭의 직경(r=-0.32**), 간장(r=0.39**), 수장(r=0.57**), 분열(r=-0.28**), 식물모양(r=0.43**), 관능검사(r=0.25*)간에는 유의성 있는 상관관계가 있었다. 5. 개화기와 초형(r=0.43**), 초형과 수형(r=0.49**), 수형과 관능검사(r=0.43**)간에는 각각 고도의 유의성이 있는 상관관계를 보였다. 6. 선발된 우량 계통의 기원은 조생계통으로 Upmost(Breeding line 1, 2), Ia2132(35), UFYS1314(62), HMX2384S(66)이었고, 만생계통으로 Krispy King(22, 54, 56), Prime Time(24), HMX2345BS(51)이었다. Upmost에서 2개의 조생계통이 유래되었고, Krispy King에서 3개의 만생계통이 유래된 것으로 보아 이 유전자원이 각각 조생, 만생계통 육성을 위한 육종재료로 활용하는 것이 바람직하다고 생각된다. 7. 선발된12개 계통에 대한 발아실험결과, Breeding line 1(40%), 33(67%), 49(77%)는 발아력이 낮았다. 저온하의 발아율은 41%이었고, 정상온도 하에서 평균 발아력은 83%이었으며, 일부 계통은 저온하에서도 60% 이상의 발아율을 나타내었다. Collection of germplasm is important for the successful breeding work of sweet corn(Zea mays L.). Genetic variation of sweet corn is more narrow and limited than that of field corn. Since most sweet corns are used to consumption for human, quality characters are more important than quantitative characters for the sweet corn breeding; However, the selection effect for the qualitative characters is much lower than that of quantitative characters. Introduced commercial super sweet corn hybrids and populations were selfed and selected according to the phenotypic performance. The selected lines were tested for their combining abilities with 3 testers at the Agricultural Experiment Station of the Dongguk University in 2000. Major agronomic characters including ear quality characters such as bite test were observed and superior breeding lines were selected based on the GCA. And germination tests were performed on selected elite breeding lines. The obtained results are summarized as follows: 1) Superior inbred lines which were shown low GCA for flowering and ear quality characters were selected. 2) Among the selected lines, five lines would be classified to early maturity groups and five lines to late maturity group. 3) GCA for days to tasseling had no trend with number of kernel row, number of kernels per row, ear length, ear aspect, and plant aspect. 4) Highly significant correlations were showed between days to tasseling and plant aspect(r=0.44**), between plant and ear aspects(r=0.49**), and between ear aspect and bite test(r=0.43**). 5) The origins of selected breeding lines were as follow; Upmost, Ia2132. UFYC1314, HMX2384S, Krispy King, Prime Time, Top Notch, Seneca Apploosa, and HMX2345BS. 6) Mean germination rates were 41% and 83% under low and normal temperature conditions, respectively. Some lines showed good germination under low temperature condition.

      • Study of antiviral activities of HCV genome replication inhibitors and their antiviral mechanism of actions

        이성진 Dongguk University 2017 국내박사

        RANK : 231951

        C 형 간염 바이러스 (HCV)는 만성 간염, 간경화 및 간암 등 간질환을 유발하는 임상 적으로 중요한 바이러스이다. 현재의 기본적인 HCV 치료 요법으로는 인터페론 알파와 리바비린 을 사용한다. 인터페론 알파와 리바비린의 경우 낮은 임상 효능과 심각한 부작용을 가지고 있다. 따라서 이보다 안전하고 효과적인 항 바이러스 약물을 개발하기 위해 저 분자 라이브러리 스크리닝을 통해 바이러스 게놈 복제를 억제하는 전임상 후보 화합물을 찾고 메커니즘을 확인한다. 이 연구에서 renilla luciferase-linked HCV replicon 세포를 이용하였고 WST 와 renilla luciferase 활성 실험 방법을 통해 세포 독성과 항 바이러스 효능을 분석 했다. 이 후 낮은 세포 독성과 매우 강력한 항 HCV 복제 활성을 나타내는 여러 화합물 및 천연물을 확인했다 High throughput screening 을 통해 HCV 복제 억제 제를 발견하기 위해 Renilla luciferase-linked genotype을 사용하여 6500 개의 합성 화합물과 344 개의 전통적인 아시아 식물 추출물을 스크리닝 했다. HCV 복 제 저해활성을 갖는 인돌 화합물 12 와 올리고스틸벤을 함유하는 포도근 추출물을 발견했다. 첫 번째 3개 그룹의 인돌 화합물 유도체가 합성되었고 HCV 복제 저해에 대한 효과를 확인하였다. 인돌 화합물 유도체에 대한 구조 활성 연구에서 E)-N-(4-tert-butylphenyl)-3-(5-cyano-1H-indol-3-yl)-2-methylacrylamide (12e)가 가장 낮은 세포 독성 (EC50 = 1.1 μM, EC90 = 2.1 μM 및 CC50 = 61.8 μM)을 보였고 또한 HCV RN 복제를 저해 하는 가장 강력한 억제제로 확인 하였다. 이후 유전자형 2a (J6 / JFH1) HCV RNA 와 유전자형 1b (Bart79I sub genome replicon) HCV RNA를 transfection 한 세포에서 바이러스 RNA 수준 과 단백질 저해 수준을 확인 한 결과 용량 및 시간 의존적으로 감소 시키는 것을 확인하였다. 메커니즘 연구를 위해12e에 내성을 갖는 돌연변이 바이러스의 유전자 분석 연구를 수행하였다. 12e 의 내성을 같은 돌연변이 HCV 의 유전자 분석 결과를 통해 HCV 의 NS5B RNA 중합 효소가 12e의 잠재적 표적이 될 수 있다고 확인 했다. 이 결과를 토대로 in-vitiro NS5B RNA 중합효소 활성 실험을 통해 12e가 RNA 중합효소를 억제 하는 것을 입증하였다 (IC50 = 292nM). 또한 PCR array 분석을 수행 한 결과, 12e가 CXCL-8, IL-1α, TNF-α, IL-3, IRAK-1, DDX58 등의 항 염증성 사이토카인 유전자의 전사를 활성화 한다는 것을 발견했고 12e가 HCV 복제 억제 활성을 가진 가용성 인자의 분비를 유발 할 수 있음을 발견하였다. 더 나아가, 재조합 CXCL-8 단백질을 처리한 HCV 감염 세포에서 HCV 복제를 감소시키는 것을 확인 하였다. 두 번째로344 개의 전통 아시아 식물로 구성된 에탄올 추출물 라이브러리를 이용하여 세포 기반 스크리닝을 수행했다. 스크리닝 결과 포도 덩굴 뿌리 추출물 (GRE)이 세포 독성 없으며 강력한 HCV 복제 억제 활성을 가지고 있었다. GRE를 분석한 결과 resveratrol tetramer 구조인 vitisin B가 HCV 복제를 억제 (EC50 = 6nM 및 CC50> 10μM) 하며 나노 몰 단위의 활성을 보였다. 또한, vitisin B와 NS5B polymerase inhibitor (sofosbuvir)의 병용 치료는 시너지 효과 또는 적어도 추가적인 항 바이러스 활성을 보였다. Vitisin B 는 다수의 vitisin B 내성 HCV 변이의 유전자 분석을 통해 NS3 헬리케이즈를 vitisin b의 표적으로 밝혀 냈다. DARTS assay를 통해 vitisin B와 NS3 helicase 사이의 직접적인 결합을 확인 했고 시험관 내 헬리케이즈 저해 확인 실험 에서 vitisin B 가 HCV NS3 헬리케이즈 (IC50 = 3 nM) 를 강력하게 저해 하는 것을 확인했다. 마지막으로, 임상 적으로 유효한 농도의 vitisin B 를 쥐에게 복막 주사 후 확인 한 결과 vitisin B가 간에 분포하는 것을 관찰했다. 두 가지의 HCV RNA복제의 강력한 저해제 인 12e 와 vitisin B를 발견하였고 더 나아가 HCV RNA복제 억제 메커니즘을 밝혀냈다. 12e는 NS5B RNA중합효소를 억제하고, 항 염증성 및 항 바이러스 사이토카인 유전자를 유도하여 HCV RNA를 복제를 저해 하는 것을 확인 하였다. 또한 강력한 HCV 복제 저해제인 vitisin B는 NS3 헬리케이즈 에 직접 결합하여 NS3 헬리케이즈 활성 저해를 통해 HCV RNA 복제를 억제한다. 이로써12e와 vitisin B가 가까운 장래에 새로운 HCV 치료제로 사용될 수 있기를 희망한다. Hepatitis C virus (HCV) is a clinically important pathogen responsible for fatal liver diseases including chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Although interferon alpha and ribavirin are two key components of current standard anti-HCV therapy, they have shown a suboptimal clinical efficacy and serious side effects. Therefore, in order to develop more safe and efficacious antiviral drugs, I aimed to identify preclinical candidate compounds which inhibit virus genome replication through small molecules library screening. In this study, I tested anti-HCV replication activities as well as cytotoxicities of in-house compounds and natural plants extracts by using a renilla luciferase-linked HCV replicon and a WST-based cell viability assay. I identified several compounds which exhibited a highly potent anti-HCV replication activity with a minimal cytotoxicity. In order to identify the inhibitors of HCV replication with a novel scaffold via a mechanistically unbiased approach, I screened our in-house library composed of 6500 synthesized compounds and 344 traditional Asian herbal plants extracts with various chemical structures by using the renilla luciferase-linked genotype 2a reporter virus, and I identified a series of compounds containing either indole or oligostilbene moieties that were active against HCV replication. First, three groups of indole derivatives were synthesized and their inhibitory effects on HCV replication were evaluated. In the present structure activity relationship study of these indole derivatives, I discovered that (E)-N-(4-tert-butylphenyl)-3-(5-cyano-1H-indol-3-yl)-2-methylacrylamide (12e) was the most potent inhibitor of HCV replication with a minimal cytotoxicity (EC50 = 1.1 μM, EC90 = 2.1 μM, and CC50 = 61.8 μM). Also I confirmed that 12e caused a dose- and time- dependent reduction of viral RNA as well as viral protein levels in both genotype 2a J6/JFH1 RNA-transfected cells and genotype 1b Bart79I sub-genomic replicon cells. I performed genetic mapping study of mutant viruses resistant to 12e. This study suggested that NS5B RNA polymerase could be a potential target for 12e. This finding was further validated by demonstration of inhibition of NS5B RNA polymerase in vitro by 12e (IC50 = 292 nM). Also I performed PCR array analyses and found that 12e was able to activate transcription of a number of pro-inflammatory as well as antiviral cytokine genes including CXCL-8, IL-1α, TNF-α, IL-3, IRAK-1, and DDX58. Their induction by 12e was verified by individual RT-PCR analyses. I found that 12e was able to stimulate secretion of soluble factors with an anti-HCV replication activity. Interestingly, a recombinant CXCL-8 protein was also able to reduce HCV replication. Second, I performed cell-based screening of an ethanol extract library composed of 344 traditional Asian herbal plants. I found that the grapevine root extract (GRE) possessed the greatest anti-HCV replication activity with a minimal cytotoxicity. Particularly, the resveratrol tetramer, vitisin B from GRE showed single-digit nanomolar potency against HCV replication (EC50 = 6 nM and CC50> 10 μM). In addition, combined treatment of vitisin B with an NS5B polymerase inhibitor (sofosbuvir) exhibited a synergistic or at least additive antiviral activity. Analysis of a number of vitisin B-resistant HCV variants suggested an NS3 helicase as its potential target. I confirmed a direct binding between vitisin B and a purified NS3 helicase in vitro. I also found a potent inhibitory activity of vitisin B against an HCV NS3 helicase (IC50 = 3 nM) in vitro. Finally, I observed that a preferred tissue distribution of vitisin B in the liver after a peritoneal injection into rats at clinically attainable concentrations. In conclusion, I discovered 12e and vitisin B, potent inhibitors of HCV replication and identified a mechanism of HCV replication. 12e inhibit NS5B polymerase, and induction of pro-inflammatory genes as well as antiviral cytokine genes. Also vitisin B was directly binding NS3 helicase and inhibit HCV replication through inhibition of NS3 helicase activity. I hope that 12e and vitisin B could be further developed in the near future to serve as a new class of anti-HCV therapeutics with a novel mode of action.

      • Bootstrap-based kNN novelty weight control chart for non-normal multivariate processes

        류이치 Dongguk University 2017 국내석사

        RANK : 231951

        Statistical process control methods have been widely used to improve processes reducing variations and preventing defects. The control chart is one of the most important statistical process control tools that can monitor processes and improve product quality. The traditional control charts mostly require a specific probability distribution to set up their control limits. But in modern manufacturing, the processes always have a great deal of complexity and variability. Most existing control charts cannot efficiently deal with situations that the patterns of observations are nonlinear or multimodal. One recent trend about control charts is based on the novelty score algorithms which can effectively describe and reflect the characteristics of the data monitored. In this paper, we propose a bootstrap-based kNN novelty weight control chart (kNW chart) that can efficiently monitor a process when observations' distribution is unknown. This control chart is based on a simulation study which is conducted to evaluate its performance. And it is also compared with the traditional (bootstrap) Hotelling's T2 control charts and some of the novelty score-based multivariate control charts. The comparative performance showed that the proposed kNW chart is acceptable to be used and has its own advantages in an interpretation of monitoring statistics.

      • Design, synthesis and characterization of dihydrodipyrrolo pyrazine derivative for optoelectronic applications

        Meti, Puttavva Dongguk University 2018 국내박사

        RANK : 231951

        Pyrazine is an important molecular scaffold employed in organic optoelectronic materials. Here we report efficient methods for the synthesis of dipyrrolopyrazine, and pyrrolothieno-pyrazine derivatives that involve regio-selective amination reactions of dihalopyrrolopyrazines. The developed protocol readily affords either 2-amino- or 3-aminopyrrolopyrazines from the corresponding 2-bromo-3-chloro-5H-pyrrolo[2,3-b]pyrazines. When the amination reactions are carried under metal free under microwave irradiation, 3- amino-pyrrolopyrazines are obtained exclusively. In contrast, Buchwald cross coupling of the 2-bromo-3-chloro-5H-pyrrolo[2,3-b]pyrazines affords only 2-amino-pyrrolopyrazine. The pyrrolopyrazine scaffolds were converted to the respective 1,7- and 1,5-dihydrodipyrrolo[2,3- b]pyrazines derivatives using Sonogashira reactions. A comprehensive study of the optical properties, thermal properties, and molecular packing of the synthesized compounds was carried out. The results indicate that the 1,5-derivatives may be promising organic materials for optoelectronic applications. Microfibers and nanorods with promising application in optoelectronics are desirable in current material synthesis. Synthetic method has been developed for the preparation of dipyrrolopyrazine derivatives by employing palladium catalysed Buchwald and Sonogashira coupling reactions. A comprehensive study on the synthesis, optical properties, thermal stability and morphology of DP-DPP derivatives were carried out. Surface morphological analysis showed the formation of microfibers, square facets and nanorods. Electrochemical studies revealed HOMO energy levels in the range of -5.10 to -5.88 eV and LUMO energy levels in the range -2.49 to -3.12 eV. All compounds exhibited a high degree of thermal stability and decomposition temperature of 322-372 oC. The enhanced air durability and thermal stability combined with good morphology makes DPP as a promising candidate for optoelectronic application. Further we extended our work with thiophene to construct D-A molecules. Synthesis and characterization of two new D-A-D molecules have been reported via Pd catalyzed C–C and C–N coupling reactions. The dipyrrolopyrazine scaffold comprises an electron-accepting core flanked by two thiophene moieties. To reveal the molecular geometry and molecular packing of 3DT-DPP, X-ray single crystal analysis was carried out. The surface morphological analysis shows the formation of microrods. The photophysical properties of these systems were characterized by UV-Vis, fluorescence spectroscopy, and cyclic voltammetry. The thermal properties reveal that both the isomers are thermally stable up to 300 oC. This study clearly demonstrates that DT-DPP can be used to build D-A molecules to produce promising conjugated materials for various optoelectronic applications.

      • Corporate governance systems and firm performance evidence from Tunisia

        Turki, Zayneb Dongguk University 2018 국내석사

        RANK : 231951

        This paper aims to contribute to the corporate governance literature in emerging economies by examining the effect of some corporate governance factors on firm performance in Tunisian listed companies. A multiple regression model is used to examine the association between firm performance and corporate governance systems in listed Tunisian companies for a sample period of 3 years (2014-2016). In particular, it examines the effect of board size, duality, institutional investors, audit type and gender diversity on the performance proxy Return on Asset ROA. Although some researchers tackled corporate governance effects on Tunisian firms and financial institutions performance, to the best of our knowledge, no study yet has examined the influence of corporate governance on firm performance in Tunisia after the Arab Spring (Tunisian revolution 2010), which shed a new light on corporate governance factors effectiveness in developing economies. The result of this research analysis indicates a positive relation between duality, number of females on the board and the performance of the firm, but it shows a negative relation between the percentage of institutional investors and Return on Asset. The results of this study may be of interest to managers who should be aware of the importance of the implementation of effective internal and external corporate governance systems, while embracing international corporate governance standards. These findings can also be beneficial to policy makers by attracting their attention to important issues related to corporate governance and firm performance. This will allow them to put in place effective corporate governance systems by improving its current corporate governance framework.

      • Effects of Scutellaria baicalensis extract on pharmacokinetics, tissue exposure and pharmacodynamics of metformin in rats

        Yim, Sreymom Dongguk University 2017 국내석사

        RANK : 231951

        Drug-herbal combination therapies have been reported to have synergistic efficacy and safety on anti-diabetic agents. Diabetes mellitus is a multi-factorial disease accompanying with other metabolic diseases which requires chronic therapy. Metformin was used for diabetes mellitus treatment in combination with herbs. Due to the possession of anti-diabetic and anti-obesity activities, the metformin combined Scutellaria baicalensis have been known for clinical potential effects in disease treatments. Organic cation transporter (OCT) and multi-drug and toxin extrusion protein (MATE) are involved in metformin distribution to liver, the target organ for glucose control, and kidneys, the main eliminating organ. Therefore, we investigated the effects of S. baicalensis extract (SB) on metformin pharmacokinetics and distribution focusing on OCT or MATE-mediated interactions. SB inhibited metformin uptake via OCT1 and MATE1 in in vitro, while metformin pharmacokinetics were not altered by 1-day, 7-day or 28-day metformin treatment with and without SB. However, higher hepatic concentrations of metformin were observed in rats receiving metformin with SB for 28 days exhibited strong inhibition of hMATE1 and slightly low inhibition of hOCT1, showed the increases of glucose lowering effect of metformin. SB treatment did not affect renal distribution or excretion of metformin, since rOCT2, metformin elimination controller, was not inhibited by SB. These results suggested that transporter-mediated interactions between metformin and SB were different during systemic exposure and in specific tissues. The determination of potential efficacy of this combination therapy was taken in order to control glucose level in blood. 당뇨병은 대사성 질환을 수반하는 만성적 질병으로 약물-천연물 병용 요법이 항당뇨 치료 요법으로 널리 이용되고 있다. Scutellaria baicalensis (SB)의 추출물이나 유효성분은 메트포르민과 함께 항당뇨 및 항비만에 효과를 나타낸다는 보고가 있으나, 약동학적 상호작용에 관한 연구는 미흡한 실정이다. 특히 유기 양이온 전달체 (OCTs)와 복합약물 및 독소압출 단백질 (MATEs)은 주로 간과 신장에 분포하며, 메트포르민의 간 또는 신장 분포를 조절한다. 메트포르민은 혈당 조절의 주요 기관인 간에서는 포도당 생성을 억제하며, 신장은 메트포르민의 주 배설 기관이다. 따라서 SB와 메트포르민 병용투여시 OCTs 쪼는 MATEs를 경유한 메트포르민의 분포 및 배설의 변화가 메트포르민의 효능 및 안전성에 영향을 줄 수 있다. 이에 본 연구에서는 SB와 메트포르민이 OCTs 및 MATEs 에서의 상호작용과 약물 동력학 및 체내 분포에 관하여 상호작용을 평가하였다. SB는 시험관에서 OCT1 과 MATE1을 통한 메트포르민 uptake를 억제하였다. 하지만 1, 7 그리고 28일 동안 메트포르민 단독 투여 및 SB와 메트포르민 병용 투여 시 메트포르민의 약동학적 파라미터는 유의한 차이가 없었다. 그러나 28동안 SB와 메트포르민 변용 투여 시, 간에서 메트포르민의 농도가 증가하였는데, 간에서 MATE1의 저해로 인한 메트포르민의 uptake감소에 의한 것으로 보인다. 이는 메트포르민 보다 효율적인 혈당 강하 효과에 영향을 주었다. 그에 반해 28일동안 SB와 메트포르민 병요 투여 시 SB는 메트포르민의 신장 분포와 배설에 영향을 주지 않았으며, 이는 SB에 의해 메트포르민 제거를 조절하는 OCT2가 영향을 받지 않았기 때문이다. 이 연구의 결과는 메트포르민 그리고 SB의 전신노출과 특정 수송체를 경유하는 약동학적 상호작용이 낮으며, 체내의 당 조절 효과는 증가한다는 결과를 보여주었다. 이는 메트포르민과 천연물과의 병용 요법의 가능성 및 평가 방법을 제시하였다.

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