• Title/Summary/Keyword: Natural product

Search Result 3,145, Processing Time 0.029 seconds

An International Collaborative Program To Discover New Drugs from Tropical Biodiversity of Vietnam and Laos

  • Soejarto, Djaja D.;Pezzuto, John M.;Fong, Harry H.S.;Tan, Ghee Teng;Zhang, Hong Jie;Tamez, Pamela;Aydogmus, Zeynep;Chien, Nguyen Quyet;Franzblau, Scott G.;Gyllenhaal, Charlotte;Regalado, Jacinto C.;Hung, Nguyen Van;Hoang, Vu Dinh;Hiep, Nguyen Tien;Xuan, Le Thi;Hai, Nong Van;Cuong, Nguyen Manh;Bich, Truong Quang;Loc, Phan Ke;Vu, Bui Minh;Southavong, Boun Hoong
    • Natural Product Sciences
    • /
    • v.8 no.1
    • /
    • pp.1-15
    • /
    • 2002
  • An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.

The Effect of Gingko Biloba Extract on Energy Metabolic Status in C3H Mouse Fibrosarcoma : Evaluated by in vivo $^{31}P$ Magnetic Resonance Spectroscopy (Gingko biloba extract가 C3H 마우스 섬유육종의 에너지 대사 상태에 미치는 영향 : 생체내 $^{31}P$ 자기공명 분광법을 이용한 분석)

  • Ha Sung Whan;Kim Won Dong;Ahn Yong Chan;Park Chan Il;Lim Tae Hwan;Lee Tae Kuen
    • Radiation Oncology Journal
    • /
    • v.20 no.2
    • /
    • pp.147-154
    • /
    • 2002
  • Purpose : Gingko biloba extract (GBE), a natural product extracted from Gingko leaves, is known to increase the radiosensitivity of tumors. This radiosensitization probably arises from the increase in the peripheral blood flow by decreasing the blood viscosity and relaxing the vasospasm. The influence of a GBE on the metabolic status in fibrosarcoma II (FSall) of a C3H mouse was investigated using $^{31}P$ magnetic resonance spectroscopy (MRS). Materials and Methods : Eighteen C3H mice with fibrosarcoma II $(from\;100\;mm^3\;to\;130\;mm^3)$ were prepared for this experiment. The mice were divided into 2 groups; one (9 mice) without a priming dose, and the other (9 mice) with a priming dose of GBE. The GBE priming dose (100 mg/kg) was administered by an intraperitoneal (i.p.) injection 24 hours prior to the measurement. First $^{31}P$ MRS spectra were measured in the mice from each group as a baseline and test dose of GBE (100 mg/kg) was then administered to each group. One hour later, the $^{31}P$ MRS spectra were measured again to evaluate the change in the energy metabolic status. Results : In the group without the priming dose, the mean pH, PCr/Pi, PME/ATP, Pi/ATP, PCr/(Pi+PME) values 1 hour after the test dose were not changed significantly compared to the values at the baseline. However, in the group with the priming dose, the mean PCr/Pi, Pi/ATP, PCr/(Pi+PME) values 1 hour after the test dose changed from the baseline values of 0.49, 0.77, 0.17 to 0.74, 0.57, 0.28 respectively. According to the paired t-test, the differences were statistically significant. Conclusion : The above findings suggest that the metabolic status is significantly improved after administering GBE if the priming dose is given 24 hours earlier. This shows that the radiosensitizing effect of GBE is based on the increase of tumor blood flow and the improvement in the metabolic status.

Experimental Study for the Development of the Mixing Ratio as a Compaction Pile (다짐말뚝 재료로서 쇄석과 저회의 적정 혼합비 도출을 위한 실험적 연구)

  • Leem, Hansoo;Kim, Sunkon;Lee, Jooho;Chun, Byungsik
    • Journal of the Korean GEO-environmental Society
    • /
    • v.13 no.9
    • /
    • pp.5-16
    • /
    • 2012
  • In the case of using the soil materials created by cutting in-situ ground directly without adjusting particle size, it is recommendable to seek the compaction property or material constant required for filling design or density control through indoor test, and many studies on this subject have been carried out during that time. The researches conducted during that time, however, were focused on the mixed materials with different diameters that exist in a natural condition. There has been no study conducted using coal fly ash that is by-product of the thermal power plant that is actively considered as the building materials. Therefore, this study was aimed at implementing compaction test and examining the basic engineering property in order to explore the influence of crushing the particles through compacting the admixture of crushed stone and coal fly ash produced from thermal power plant on its engineering property, and then the impact of the admixture volume of each material on compaction property and material property by conducting the One-Dimensional Compression Test. As result of compaction test, the optimum moisture ratio of coal fly ash was shown to be approx. 23%. As result of compaction test in accordance with the mixed ratio of coal fly ash and crushed stone under the same compaction energy and moisture ratio, dry unit weight tended to drop when the mixed ratio of coal fly ash exceeded 30%, while it reached approx. $1.81gf/cm^3$ when the mixed ratio was 30%. As result of One-Dimensional Compression Test in accordance with the mixed ratio of crushed stone and coal fly ash, the change in void ratio by particle crushing was at the highest level in the case of coal fly ash 100%, while the lowest level in the case of crushed stone 100%. In the case of mixed materials of crushed stone and coal fly ash, compression index was at the lowest level in case of coal fly ash 30%, and therefore this ratio of mixed material was judged to be the most stable from an engineering aspect.

Suppressive effects of ethanol extract of Aralia elata on UVB-induced oxidative stress in human keratinocytes (자외선 B를 조사한 인간유래각질세포에서 두릅순 에탄올추출물의 산화적 스트레스 억제효과)

  • Kwak, Chung Shil;Yang, Jiwon
    • Journal of Nutrition and Health
    • /
    • v.49 no.3
    • /
    • pp.135-143
    • /
    • 2016
  • Purpose: Ultraviolet (UV)-induced oxidative stress contributes to several adverse biological effects on skin. Many phenolic phytochemicals have been shown to have antioxidant properties and protect skin cells from UV-induced oxidative damage. In this study, we investigated whether or not Aralia elata (AE) has a protective effect against UVB-induced reactive oxygen species (ROS), ultimately leading to photoaging. Methods: Phenolic content of dried AE and antioxidant properties of AE extract in 70% ethanol weredetermined by measuring DPPH and ABTS radical scavenging activities and ferric reducing antioxidant power (FRAP). The effect of AE extract on cellular ROS generation and expression levels of oxidative stress-response proteins such as superoxide dismutase (SOD)-1, catalase, nuclear factor-erythroid 2-related factor (Nrf)-2, and heme oxygenase (HO)-1 in UVB-irradiated ($75mJ/cm^2$) human keratinocytes (HaCaT) were further determined by 2'-7'-dichlorofluoresceine diacetate assay and Western blotting, respectively. Results: The total phenolic and flavonoid contents of dried AE were 20.15 mg tannic acid/g and 18.75 mg rutin/g, respectively. The $IC_{50}$ of AE extract against DPPH radical was $98.5{\mu}g/mL$, and ABTS radical scavenging activity and FRAP upon treatment with $1,000{\mu}g/mL$ of AE extract were $41.8{\mu}g\;ascorbic\;acid\;(AA)\;eq./mL$ and $29.7{\mu}g\;AA\;eq./mL$,m respectively. Pretreatment with AE extract significantly reduced (p < 0.05) ROS generation compared to that in UVB-irradiated control HaCaT cells. Pretreatment with AE extract reversed reduction of Nrf-2 and SOD-1 protein expression and induction of HO-1 protein expression caused by UVB exposure in HaCaT cells, whereas it did not affect catalase expression. Conclusion: AE extract in 70% ethanol demonstrated a protective effect against UVB-induced oxidative stress and decreased expression of Nrf-2 and SOD-1 in human keratinocytes. These findings suggest that AE ethanol extract might have potential as a natural resource for a skin anti-photoaging product in the food and cosmetic industry.

Interpretation of C.C.L.Hirschfeld's Theory of Garden Art in Contemporary Meaning and Its Significance (히르시펠트(C.C.L.Hirschfeld) 정원예술론의 의미와 가치의 현대적 해석)

  • Zoh, Kyung-Jin
    • Journal of the Korean Institute of Traditional Landscape Architecture
    • /
    • v.32 no.3
    • /
    • pp.58-68
    • /
    • 2014
  • Christian Cay Lorenz Hirschfeld is often regarded as 'a father of landscape garden art.' He was an aesthetics professor and garden theoretician in the $18^{th}$ century. He put forth the most comprehensive garden theory book in five volumes between 1779 and 1785. His book, Theorie der Gartenkunst, was translated and widely circulated in his contemporary. The book, which dealt with diverse aspects of garden art such as history, design, material, and type, urged to promote the prevalence of landscape garden in European continents as well as in Germany. However, there have scarcely been discourses in the Hirschfeld's garden theory. This essay aims to review Hirschfeld's garden thoughts in his book critically and to reinterpret some issues in the contemporary landscape theory and practice. Hirschfeldian theory was the product of $18^{th}$ century German Enlightenment and romanticism. At that time, Nature was regarded as divine realm. There was a German affinity with natural world. The spread of reading culture and the fashion of travel literature were another background of the success of his garden literature. Several issues in Hirschfeld garden theory will discussed here. First, privileging garden art was the most significant contribution in his theory. He emphasized that garden art was the most advanced art form among all art genres. Second, garden art was grounded on the mimesis of nature. The ambiguous relationship between nature and art still existed in garden making. However, garden art can be flourished when utilizing the potency of nature in itself. Third, there was the association between the image and the idea in experiencing the garden. Some garden scenes stimulated the related emotional responses such as cheerful and merry, softly melancholic, romantic, solemn etc. Fourth, the movement was the essential aspect of garden art. Motion and emotion are come together in garden experience. To represent the landscape garden style in suitable way, the sketch or image seems to be preferable than the plans and views. Finally, garden art was composing of not only the physical space but also the spirit of place. He maintained the garden art as hortus moralis should be a social metaphor. Hirschfeldian garden theory has often been criticized as the lack of practical power and the old fashioned idea. However, his theory influenced on formulating the idea of public park in $19^{th}$ century. Moreover, there are still some visionary aspects of his theory such as the reevaluation of garden art, the emphasis of locality and the introduction of Mittelweg idea. Recently, gardening culture are prevalent in various realms of art and life. Hirschfeld's garden theory as humanistic landscape theory can provide us some insights in the contemporary practices.

consumers' purchasing behavior of functional cosmetics and Inula based functional cosmetics merchandising research (국내 소비자의 기능성화장품 구매행태 및 선복화 활용 기능성화장품 상품화를 위한 연구)

  • Han, Do-Kyung;Lee, Hyun-Jun;Lee, Eun-Hee;Paik, Hyun-Dong;Shin, Dong-Kyoo;Park, Dae-Sub;Hwang, Hye-Seon;Hong, Wan-Soo
    • Journal of the Korea Academia-Industrial cooperation Society
    • /
    • v.17 no.8
    • /
    • pp.236-250
    • /
    • 2016
  • This study was conducted to provide baseline data regarding functional cosmetics so that Inula. based cosmetics can increase its competitiveness in the market as well as to understand current trends to enable anticipation of demands for future product development. For this research, general consumers over the age of 20 residing in Seoul and the Gyeonggi district were surveyed. The results show consumers preferred serum-type products among various types of cosmetics, and that they purchased these once every 1-3 months. Consumers also preferred these products in less than 10-30ml capacity, and at costs of less than 30,000-50,000 KRW. For whitening, functional cosmetics consumers also preferred the serum type, in less than 30-50ml capacity and priced less than 30,000-50,000 KRW. Consumers preferred to purchase functional cosmetics in single units. The major purchasing location, with a high preference rate, was cosmetic stores, and the major sources of information, also with high preference rates, were 'experienced reviews from family, friends and acquaintances' and 'TV advertisements'. Respondents selected 'over 50,000 KRW' the most for all items when responding to 'Purchase Intent for Functional Cosmetics containing Inula', and responded that they were willing to pay 10%-30% more for functional cosmetics containing Inula compared to standard functional cosmetics. These results show that businesses in the cosmetics industry need to take consumer demand into account when developing new functional cosmetic products, as well as establish plans to create specialized spaces that provide better quality service and increase word of mouth effect through better utilization of various types of offline media, social media, and blogs. The study also shows a need for businesses to develop products fully utilizing the Inula flower, which has been shown to be effective as a natural skin whitener, wrinkle reducer and skin moisturizer, to appeal to the increasing number of customers interested in health and beauty.

Kinetics and mechanism of hydrolysis of insecticidal buprofezin (살충제 buprofezin의 가수분해 반응 메카니즘)

  • Sung, Nack-Do;Yu, Seong-Jae;Choi, Kyung-Sub;Kwon, Ki-Sung
    • The Korean Journal of Pesticide Science
    • /
    • v.2 no.1
    • /
    • pp.46-52
    • /
    • 1998
  • The hydrolysis rate of insecticidal buprofezin(IUPAC : tert-butylimino-3-isopropyl-5-phenylperhydro-1,3,5-thiadiazin-4-one) in the range of pH 2.0 and 12.0 have been examined in 15%(v/v) aqueous dioxane at $45^{\circ}C$. The hydrolysis mechanism of buprofezin is proposed from the pH-effect, solvent effect(${\ell}{\gg}m$), thermodynamic parameter(${\Delta}H^{\neq}$=11.12 $Kcal{\cdot}mol^{-1}$ &, ${\Delta}S^{\neq}=5.0e.u.$), rate equation and hydrolysis product, l-isopropyl-3-phenyl urea. General acid catalyzed hydrolysis and specific acid catalyzed($k_{H3O+}$) hydrolysis through $A-S_{E}2$ and A-2(or $A_{AC}2$) reaction mechanism with orbital-control reaction proceed below pH 8.0 and above pH 9.0, the nucleophilic addition-elimination, $Ad_{N}-E$ mechanism via tetrahedral($sp^{3}$) intermediate is initiation by general base catalyzed($k_{H2O}$) reaction. Buprofezin was more stable in alkaline ($k=10^{-8}sec.^{-1}$) than acid solutions from the sigmoid pH-rate profile. And the half-life($t=\frac{1}{2}$) of hydrolysis reaction in neutral aqueous solution(pH 7.0) at $45^{\circ}C$ was about 3 months.

  • PDF

Studies on the Chemical Constituents of the New Zealand Deer Velvet Antler Cervus elaphus var. scoticus-(I)

  • Lee, Nam Kyung;Shin, Hyun Jung;Kim, Wan Seok;Lee, Jong Tae;Park, Chae Kyu
    • Natural Product Sciences
    • /
    • v.20 no.3
    • /
    • pp.160-169
    • /
    • 2014
  • 44 compounds and 9 minerals were isolated from and detected in the New Zealand deer velvet antler Cervus elaphus var. scoticus L$\ddot{o}$nnberg. The chemical structures of (1 - 26) were identified on the basis of the spectroscopic methods and comparisons with literature, respectively. The structures were identified as cholesterol (CS, 6), 7-keto-CS (7), $7{\beta}$-hydroxy-CS (8), and $7{\alpha}$-hydroxy-CS (9), and included 12 steroid $3{\beta}$-O-(palmitic/stearic/myristic acid esters; PM/SA/MS) [CS-$3{\beta}$-O-PM (1 - 1), CS-$3{\beta}$-O-SA (1 - 2), CS-$3{\beta}$-O-MR (1 - 3), 7-keto-CS-$3{\beta}$-O-PM (2 - 1), 7-keto-CS-$3{\beta}$-O-SA (2 - 2), 7-keto-CS-$3{\beta}$-O-MR (2 - 3), $7{\beta}$-hydroxy-CS-$3{\beta}$-O-SA (3 -1), $7{\beta}$-hydroxy-CS-$3{\beta}$-O-PM (3 - 2), $7{\beta}$-hydroxy-CS-$3{\beta}$-O-MR (3 - 3), $7{\alpha}$-hydroxy-CS-$3{\beta}$-O-SA (4 - 1), $7{\alpha}$-hydroxy-CS-$3{\beta}$-O-PM (4 - 2), and $7{\alpha}$-hydroxy-CS-$3{\beta}$-O-MR (4 - 3)], dinonyl phthalate (5), 8 nucleic acids analogues [uracil (10), deoxyguanosine (11), deoxyuridine (12), uridine (13), deoxyadenosine (14), adenosine (15), inosine (16), and guanosine (17)], and the 9 free amino acids [L-phenylalanine (18), L-isoleucine (19), L-leucine (20), L-tyrosine (21), L-valine (22), L-proline (23), L-threonine (24), L-alanine (25), and L-hydroxyproline (26)]. Also, there are 8 kinds of amino acids [asparagine, serine, glutamine, glycine, histidine, arginine, methionine, and lysine], 2 sialic acids [N-acetylneuraminic acid (27), ketodeoxynonulosonic acid (28)], and 9 minerals [Na > K > Ca > Mg > Fe > Zn > B > Al > Cu] were detected from the autoaminoacid analyzer and ICP spectrometer, HPAEC-PAD/HPLC-FLD, respectively. 9 kinds of oxycholesterol-$3{\beta}$-O-fatty acid ester (2 - 1, 2 - 2, 2 - 3, 3 - 1, 3 - 2, 3 - 3, 4 - 1, 4 - 2, and 4 - 3) and 3 nucleic acids (12, 14, and 15) were isolated from the velvet antler for the first time. 6 kinds of steroids (7, 8, 9, 2 - 1, 3 - 1, and 4 - 1) were examined for their anti-proliferative effects against L1210, P388D1, K562, MEG-01, KG-1, MOLT-4, A549, HepG2, MCF-7, SK-OV-3, and SW-620 cancer cell lines. They showed anti-proliferative effects with $IC_{50}$ values of 0.06, 2.16, 2.42, > 50.0, 1.66 and $8.31{\mu}M$ against L1210, while the values were 24.05, 9.44, 5.22, 0.25. 9.48 and $49.77{\mu}M$ against P388D1, respectively. The others were inactive.

Preventive Effect of Milk Products against Diabetes Mellitus Type 2: A Review (유제품의 제2형 당뇨병 예방 효과: 총설)

  • Kim, Dong-Hyeon;Chon, Jung-Whan;Kim, Hyun-Sook;Kim, Hong-Seok;Song, Kwang-Young;Kim, Young-Ji;Kang, Il-Byung;Lee, Soo-Kyung;Jeong, Dong-Gwan;Kim, Soo-Ki;Seo, Kun-Ho
    • Journal of Dairy Science and Biotechnology
    • /
    • v.33 no.2
    • /
    • pp.129-137
    • /
    • 2015
  • Diabetes mellitus type 2 is a metabolic disorder that is characterized by hyperglycemia (high blood sugar level) in the context of insulin resistance and relative lack of insulin. Recently, much scientific evidence has shown that the risk of diabetes mellitus type 2 could be reduced by dairy intake. A significantly strong relationship has been noted between this disease and dairy intake. In particular, from the different types of fat in dairy foods that were reported to have a beneficial impact, low-fat dairy foods have been found to have the best effect with respect to reducing the risk of diabetes mellitus type 2. Therefore, the role of specific components of dairy foods, such as calcium, vitamin D, dairy fat, and trans-palmitoleic acid, which could be responsible for this effect and for the positive effect of dairy foods in obesity and metabolic syndrome, needs to be identified. There is a strong and relatively consistent body of accumulating evidence indicating that dairy foods may significantly reduce the risk of diabetes mellitus type 2, likely in a dose-response manner. Dairy recommendations should be an essential part of public health guidance, and identifying strategies to increase dairy food consumption to optimal levels is of utmost importance. Hence, this review summarizes various positive effects of dairy foods with respect to reducing the risk of diabetes mellitus type 2, based on available evidence, and discusses the need for further research on preventing or decreasing the risk of diabetes mellitus type 2.

  • PDF

Reduction of Mitochondrial Electron Transferase in Rat Bile duct Fibroblast by Clonorchis sinensis Infection (간흡충(Clonorchis sinensis)감염에 의한 흰쥐 담관 섬유모세포 미토콘드리아 전자전달효소의 감소)

  • Min, Byoung-Hoon;Hong, Soon-Hak;Lee, Haeng-Sook;Kim, Soo-Jin;Joo, Kyoung-Hwan
    • Applied Microscopy
    • /
    • v.40 no.2
    • /
    • pp.89-99
    • /
    • 2010
  • Fibroblasts are the most common cells in connective tissue and are responsible for the synthesis of extracellular matrix components. The fibrosis associated with chronic inflammation and injury may contribute to cholangiocarcinoma pathogenesis, particularly through an increase in extracellular matrix components, which participate in the regulation of bile duct differentiation during development. Mitochondria produce ATP through oxidative metabolism to provide energy to the cell under physiological conditions. Also, mitochondrial dysfunction and oxidative stress have been implicated in cellular senescence and aging. Alternations in mitochondrial structure and function are early events of programmed cell death or apoptosis and mitochondria appear to be a central regulator of apoptosis in most somatic cell. Clonorchis sinensis, one of the most important parasite of the human bile duct in East Asia, arouses epithelial hyperplasia and ductal fibrosis. Isolated fibroblast from the bile ducts of rats infected by C. sinensis showed increase of cytoplasmic process. In addition, decrease of cellular proliferation was observed in fibroblasts which was isolated from normal rat bile duct and then cultured in media containing C. sinensis excretory-secretory product. However, the effects of C. sinensis infection on the mitochondrial enzyme distribution is not clearly reported yet. Therefore, we investigated the structural change of C. sinensis infected bile duct and mitochondrial enzyme distribution of the cultured fibroblast isolated from the C. sinensis infected rat bile duct. As a result, C. sinensis infected SD rat bile ducts showed the features of chronic clonorchiasis, such as ductal connective and epithelial tissue dilatation, or ductal fibrosis. In addition, fibroblast in ductal connective tissue was damaged by physical effect of fibrotic tissue and chemical stimulation. Immunohistochemically detected mitochondrial electron transferase (ATPase, COXII, Porin) was decreased in C. sinensis infected rat bile duct and cultured fibroblast from infected rat bile duct. It can be hypothesized that the reason why number of electron transferase decrease in fibroblast isolated from the rat bile duct infected with C. sinensis is because dysfunction of electron transport system is occurred mitochondrial dysfunction, increase of ROS (reactive oxygen species) and apoptosis after chemical damage on the cell caused by C. sinensis infection. Overall, C. sinensis infection induces fibrotic change of ductal connective tissue, mutation of cellular metabolism in fibroblast and mitochondrial dysfunction. Consequently, ductal fibrosis inhibits fibroblast proliferation and decreases mitochondrial electron transferase on fibroblast cytoplasm. It was assumed that the structure of bile duct could not normalized and ductal fibrosis was maintained for a long period of time according to fibroblast metamorphosis and death induced by mitochondrial dysfunction.