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題名 探討紫蘇對百草枯引起果蠅毒害之影響
Effects of Perilla on Paraquat-induced Toxicity in Drosophila作者 陳玫汝 貢獻者 詹銘煥
陳玫汝關鍵詞 帕金森氏症
PINK1
Parkin
紫蘇
百草枯
果蠅
Drosophila
Parkinson’s disease
PINK1
Parkin
Perilla
Paraquat日期 2016 上傳時間 3-Aug-2016 10:15:30 (UTC+8) 摘要 帕金森氏症是現今常見的神經退化性疾病，其特徵主要表現在運動功能上的缺失包含靜止時振顫、步態不穩及肢體僵硬等特徵。而基因研究指出當PTEN-induced putative kinase 1 (PINK1)及Parkin基因發生突變可能會導致粒腺體功能失常，進而導致帕金森氏症之神經退化性疾病，另外PINK1基因突變的果蠅亦會產生嗅覺辦識功能障礙。在環境因素方面，一種廣效使用的除草劑百草枯(paraquat)被認為與誘發帕金森氏症有關。根據中醫生理學概念，消化系統功能紊亂，不但影響腸道功能亦會影響其他系統的運作,包含中樞神經系統。因此本實驗採用中草藥紫蘇初萃取物作為實驗藥物，紫蘇(Perilla frutescens)在中醫臨床的主要功能用於治療因飲食不節而導致的腸胃氣滯，進而減緩其他表症的不適感，另外紫蘇另一項功能在於能解食魚蟹之毒。因此我們評估紫蘇可能對於野生型及突變型果蠅因百草枯引發之毒性具有保護作用。實驗結果顯示，紫蘇可以有效的降低因曝露在百草枯(24-72小時)下的致死率，不論在野生型Oregon-R品系及PINK1B9或Parkin25的突變型(年齡：3-7天, 10-14天)。然而紫蘇對於果蠅的運動爬行功能只有在施予百草枯後的野生型Oregon-R 品系(年齡：3-7天)有些微改善，但是在嗅覺辨識功能被百草枯破壞的PINK1B9 突變果蠅，則能經由紫蘇而減少嗅覺辨識的損害。綜合以上實驗結果得知紫蘇對於百草枯所造成的毒性具有保護效果，期望未來可作為治療帕金森氏症的潛在藥物。
Parkinson’s disease (PD) is the most common neurodegenerative disease characterized by motor deficits including resting tremor, akinesia, and rigidity. The olfactory disturbance appears to be an earlier symptom prior to the onset of motor dysfunction in PD. Genetic research has shown that mutations of the PTEN-induced putative kinase 1 (PINK1) and Parkin genes could lead to mitochondrial dysfunction and neuronal degeneration in PD. Moreover, the environmental neurotoxin paraquat (PQ), a widely used pesticide, is known to induce PD-like symptoms. According to Traditional Chinese medicine physiology theory, that the central nervous system and gut interact bidirectionally in functional gastrointestinal disorders. Perilla frutescens, a traditional herbal medicine, is mainly prescribed for the treatment of gastrointestinal discomfort after eating and symptom of qi stagnation. In addition, perilla has an important role in detoxification of seafood intake. Therefore, this study evaluated the protective effects of perilla on paraquat-induced toxicity in Drosophila PINK1 and parkin mutants and wild type flies. Result showed that perilla can effectively alleviate lethality of drosophila, including PINK1 and parkin mutant flies, exposed to paraquat for 24-72 hours. However, their motor dysfunctions induced by paraquat were little ameliorated by perilla. Importantly, the olfactory dysfunction, particularly olfactory discrimination, elicited by paraquat in PINK1 mutant fly was improved by perilla. Taken together, our findings provide the protective potential of perilla for treatment of PD syndromes.參考文獻 Bonilla, E., Medina-Leendertz, S., Villalobos, V., Molero, L. & Bohorquez, A. (2006) Paraquat-induced oxidative stress in drosophila melanogaster: effects of melatonin, glutathione, serotonin, minocycline, lipoic acid and ascorbic acid. Neurochemical research, 31, 1425-1432.Casey, G. (2013) Parkinson`s disease: a long and difficult journey. Nursing New Zealand (Wellington, N.Z. : 1995), 19, 20-24.Chen, C.-Y., Leu, Y.-L., Fang, Y., Lin, C.-F., Kuo, L.-M., Sung, W.-C., Tsai, Y.-F., Chung, P.-J., Lee, M.-C. & Kuo, Y.-T. (2015) Anti-inflammatory effects of Perilla frutescens in activated human neutrophils through two independent pathways: Src family kinases and Calcium. Scientific reports, 5.Choi, U.-K., Lee, O.-H., Lim, S.-I. & Kim, Y.-C. (2010) Optimization of antibacterial activity of Perilla frutescens var. acuta leaf against Pseudomonas aeruginosa using the evolutionary operation-factorial design technique. International journal of molecular sciences, 11, 3922-3932.Feany, M.B. & Bender, W.W. (2000) A Drosophila model of Parkinson`s disease. Nature, 404, 394-398.Gawarammana, I.B. & Buckley, N.A. (2011) Medical management of paraquat ingestion. British Journal of Clinical Pharmacology, 72, 745-757.Hughes, J.T. (1988) Brain damage due to paraquat poisoning: a fatal case with neuropathological examination of the brain. Neurotoxicology, 9, 243-248.Jang, J.Y., Kim, T.S., Cai, J., Kim, J., Kim, Y., Shin, K., Kim, K.S., Lee, S.P., Kang, M.H., Choi, E.K., Rhee, M.H. & Kim, Y.B. (2014) Perilla oil improves blood flow through inhibition of platelet aggregation and thrombus formation. Lab Anim Res, 30, 21-27.Jankovic, J. & Aguilar, L.G. (2008) Current approaches to the treatment of Parkinson’s disease. Neuropsychiatric Disease and Treatment, 4, 743-757.Jeon, I., Kim, H., Kang, H., Lee, H.-S., Jeong, S., Kim, S. & Jang, S. (2014) Anti-Inflammatory and Antipruritic Effects of Luteolin from Perilla (P. frutescens L.) Leaves. Molecules, 19, 6941.Kim, D.-H., Kim, Y.-C. & Choi, U.-K. (2011) Optimization of antibacterial activity of Perilla frutescens var. acuta leaf against Staphylococcus aureus using evolutionary operation factorial design technique. International journal of molecular sciences, 12, 2395-2407.Makino, T., Furuta, Y., Wakushima, H., Fujii, H., Saito, K.i. & Kano, Y. (2003) Anti‐allergic effect of Perilla frutescens and its active constituents. Phytotherapy Research, 17, 240-243.Marder, K.S., Tang, M.X., Mejia-Santana, H. & et al. (2010) Predictors of parkin mutations in early-onset parkinson disease: The consortium on risk for early-onset parkinson disease study. Archives of Neurology, 67, 731-738.Ohlstein, B. & Spradling, A. (2006) The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature, 439, 470-474.Park, J., Lee, S.B., Lee, S., Kim, Y., Song, S., Kim, S., Bae, E., Kim, J., Shong, M. & Kim, J.-M. (2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature, 441, 1157-1161.Poddighe, S., Bhat, K.M., Setzu, M.D., Solla, P., Angioy, A.M., Marotta, R., Ruffilli, R., Marrosu, F. & Liscia, A. (2013) Impaired sense of smell in a Drosophila Parkinson`s model. PloS one, 8, e73156.Raudone, L., Burdulis, D., Raudonis, R., Janulis, V., Jankauskiene, L., Viskelis, P. & Trumbeckaite, S. (2016) EFFECT OF PERILLA FRUTESCENS EXTRACTS AND ROSMARINIC ACID ON RAT HEART MITOCHONDRIAL FUNCTIONS. Acta poloniae pharmaceutica, 73, 135-145.Samaranch, L., Lorenzo-Betancor, O., Arbelo, J.M., Ferrer, I., Lorenzo, E., Irigoyen, J., Pastor, M.A., Marrero, C., Isla, C., Herrera-Henriquez, J. & Pastor, P. (2010) PINK1-linked parkinsonism is associated with Lewy body pathology. Brain : a journal of neurology, 133, 1128-1142.Semchuk, K.M., Love, E.J. & Lee, R.G. (1992) Parkinson`s disease and exposure to agricultural work and pesticide chemicals. Neurology, 42, 1328-1335.Smeyne, R.J. & Jackson-Lewis, V. (2005) The MPTP model of Parkinson`s disease. Molecular Brain Research, 134, 57-66.Stefanis, L. (2012) α-Synuclein in Parkinson`s Disease. Cold Spring Harbor Perspectives in Medicine, 2, a009399.Ueda, H., Yamazaki, C. & Yamazaki, M. (2002) Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. Biological & pharmaceutical bulletin, 25, 1197-1202.Valente, E.M., Abou-Sleiman, P.M., Caputo, V., Muqit, M.M.K., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A.R., Healy, D.G., Albanese, A., Nussbaum, R., González-Maldonado, R., Deller, T., Salvi, S., Cortelli, P., Gilks, W.P., Latchman, D.S., Harvey, R.J., Dallapiccola, B., Auburger, G. & Wood, N.W. (2004) Hereditary Early-Onset Parkinson`s Disease Caused by Mutations in PINK1. Science (New York, N.Y.), 304, 1158-1160.van der Merwe, C., Jalali Sefid Dashti, Z., Christoffels, A., Loos, B. & Bardien, S. (2015) Evidence for a common biological pathway linking three Parkinson`s disease-causing genes: parkin, PINK1 and DJ-1. The European journal of neuroscience, 41, 1113-1125.伍永富, 秦少容 & 劉世琪 (2007) 紫蘇葉油的研究進展. 時珍國醫國藥, 18, 2019-2020. 描述 碩士
國立政治大學
神經科學研究所
103754009資料來源 http://thesis.lib.nccu.edu.tw/record/#G0103754009 資料類型 thesis dc.contributor.advisor 詹銘煥 zh_TW dc.contributor.author (Authors) 陳玫汝 zh_TW dc.creator (作者) 陳玫汝 zh_TW dc.date (日期) 2016 en_US dc.date.accessioned 3-Aug-2016 10:15:30 (UTC+8) - dc.date.available 3-Aug-2016 10:15:30 (UTC+8) - dc.date.issued (上傳時間) 3-Aug-2016 10:15:30 (UTC+8) - dc.identifier (Other Identifiers) G0103754009 en_US dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/99613 - dc.description (描述) 碩士 zh_TW dc.description (描述) 國立政治大學 zh_TW dc.description (描述) 神經科學研究所 zh_TW dc.description (描述) 103754009 zh_TW dc.description.abstract (摘要) 帕金森氏症是現今常見的神經退化性疾病，其特徵主要表現在運動功能上的缺失包含靜止時振顫、步態不穩及肢體僵硬等特徵。而基因研究指出當PTEN-induced putative kinase 1 (PINK1)及Parkin基因發生突變可能會導致粒腺體功能失常，進而導致帕金森氏症之神經退化性疾病，另外PINK1基因突變的果蠅亦會產生嗅覺辦識功能障礙。在環境因素方面，一種廣效使用的除草劑百草枯(paraquat)被認為與誘發帕金森氏症有關。根據中醫生理學概念，消化系統功能紊亂，不但影響腸道功能亦會影響其他系統的運作,包含中樞神經系統。因此本實驗採用中草藥紫蘇初萃取物作為實驗藥物，紫蘇(Perilla frutescens)在中醫臨床的主要功能用於治療因飲食不節而導致的腸胃氣滯，進而減緩其他表症的不適感，另外紫蘇另一項功能在於能解食魚蟹之毒。因此我們評估紫蘇可能對於野生型及突變型果蠅因百草枯引發之毒性具有保護作用。實驗結果顯示，紫蘇可以有效的降低因曝露在百草枯(24-72小時)下的致死率，不論在野生型Oregon-R品系及PINK1B9或Parkin25的突變型(年齡：3-7天, 10-14天)。然而紫蘇對於果蠅的運動爬行功能只有在施予百草枯後的野生型Oregon-R 品系(年齡：3-7天)有些微改善，但是在嗅覺辨識功能被百草枯破壞的PINK1B9 突變果蠅，則能經由紫蘇而減少嗅覺辨識的損害。綜合以上實驗結果得知紫蘇對於百草枯所造成的毒性具有保護效果，期望未來可作為治療帕金森氏症的潛在藥物。 zh_TW dc.description.abstract (摘要) Parkinson’s disease (PD) is the most common neurodegenerative disease characterized by motor deficits including resting tremor, akinesia, and rigidity. The olfactory disturbance appears to be an earlier symptom prior to the onset of motor dysfunction in PD. Genetic research has shown that mutations of the PTEN-induced putative kinase 1 (PINK1) and Parkin genes could lead to mitochondrial dysfunction and neuronal degeneration in PD. Moreover, the environmental neurotoxin paraquat (PQ), a widely used pesticide, is known to induce PD-like symptoms. According to Traditional Chinese medicine physiology theory, that the central nervous system and gut interact bidirectionally in functional gastrointestinal disorders. Perilla frutescens, a traditional herbal medicine, is mainly prescribed for the treatment of gastrointestinal discomfort after eating and symptom of qi stagnation. In addition, perilla has an important role in detoxification of seafood intake. Therefore, this study evaluated the protective effects of perilla on paraquat-induced toxicity in Drosophila PINK1 and parkin mutants and wild type flies. Result showed that perilla can effectively alleviate lethality of drosophila, including PINK1 and parkin mutant flies, exposed to paraquat for 24-72 hours. However, their motor dysfunctions induced by paraquat were little ameliorated by perilla. Importantly, the olfactory dysfunction, particularly olfactory discrimination, elicited by paraquat in PINK1 mutant fly was improved by perilla. Taken together, our findings provide the protective potential of perilla for treatment of PD syndromes. en_US dc.description.tableofcontents 圖表目錄 3縮寫表 5第一章、緒論 6 第一節、前言 6 第二節、帕金森氏病 7 第三節、帕金森氏症之治療 8 第四節、百草枯之毒害機轉及疾病動物模式 9 第五節、PINK1與Parkin病變基因 10 第六節、紫蘇的簡介 13 第七節、紫蘇的成份與藥理作用 14第二章、實驗動機與方法 16 第一節、實驗材料與方法 16 第二節、實驗動物 17 第三節、實驗藥品配置 17 第四節、實驗方法 20 第五節、實驗流程設計 22第三章、實驗結果 25 第一節、紫蘇對果蠅在百草枯毒害下之存活率影響 25 第二節、紫蘇對果蠅在百草枯毒害下之爬行能力影響 29第三節、紫蘇對果蠅在百草枯毒害下之嗅覺能力影響 31第四章、討論與結論 33 第一節、討論 33 第二節、結論 38第五章、圖表與附錄 39 第一節、圖表 39 第二節、附錄 60參考文獻 62 zh_TW dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G0103754009 en_US dc.subject (關鍵詞) 帕金森氏症 zh_TW dc.subject (關鍵詞) PINK1 zh_TW dc.subject (關鍵詞) Parkin zh_TW dc.subject (關鍵詞) 紫蘇 zh_TW dc.subject (關鍵詞) 百草枯 zh_TW dc.subject (關鍵詞) 果蠅 zh_TW dc.subject (關鍵詞) Drosophila en_US dc.subject (關鍵詞) Parkinson’s disease en_US dc.subject (關鍵詞) PINK1 en_US dc.subject (關鍵詞) Parkin en_US dc.subject (關鍵詞) Perilla en_US dc.subject (關鍵詞) Paraquat en_US dc.title (題名) 探討紫蘇對百草枯引起果蠅毒害之影響 zh_TW dc.title (題名) Effects of Perilla on Paraquat-induced Toxicity in Drosophila en_US dc.type (資料類型) thesis en_US dc.relation.reference (參考文獻) Bonilla, E., Medina-Leendertz, S., Villalobos, V., Molero, L. & Bohorquez, A. (2006) Paraquat-induced oxidative stress in drosophila melanogaster: effects of melatonin, glutathione, serotonin, minocycline, lipoic acid and ascorbic acid. Neurochemical research, 31, 1425-1432.Casey, G. (2013) Parkinson`s disease: a long and difficult journey. Nursing New Zealand (Wellington, N.Z. : 1995), 19, 20-24.Chen, C.-Y., Leu, Y.-L., Fang, Y., Lin, C.-F., Kuo, L.-M., Sung, W.-C., Tsai, Y.-F., Chung, P.-J., Lee, M.-C. & Kuo, Y.-T. (2015) Anti-inflammatory effects of Perilla frutescens in activated human neutrophils through two independent pathways: Src family kinases and Calcium. Scientific reports, 5.Choi, U.-K., Lee, O.-H., Lim, S.-I. & Kim, Y.-C. (2010) Optimization of antibacterial activity of Perilla frutescens var. acuta leaf against Pseudomonas aeruginosa using the evolutionary operation-factorial design technique. International journal of molecular sciences, 11, 3922-3932.Feany, M.B. & Bender, W.W. (2000) A Drosophila model of Parkinson`s disease. Nature, 404, 394-398.Gawarammana, I.B. & Buckley, N.A. (2011) Medical management of paraquat ingestion. British Journal of Clinical Pharmacology, 72, 745-757.Hughes, J.T. (1988) Brain damage due to paraquat poisoning: a fatal case with neuropathological examination of the brain. Neurotoxicology, 9, 243-248.Jang, J.Y., Kim, T.S., Cai, J., Kim, J., Kim, Y., Shin, K., Kim, K.S., Lee, S.P., Kang, M.H., Choi, E.K., Rhee, M.H. & Kim, Y.B. (2014) Perilla oil improves blood flow through inhibition of platelet aggregation and thrombus formation. Lab Anim Res, 30, 21-27.Jankovic, J. & Aguilar, L.G. (2008) Current approaches to the treatment of Parkinson’s disease. Neuropsychiatric Disease and Treatment, 4, 743-757.Jeon, I., Kim, H., Kang, H., Lee, H.-S., Jeong, S., Kim, S. & Jang, S. (2014) Anti-Inflammatory and Antipruritic Effects of Luteolin from Perilla (P. frutescens L.) Leaves. Molecules, 19, 6941.Kim, D.-H., Kim, Y.-C. & Choi, U.-K. (2011) Optimization of antibacterial activity of Perilla frutescens var. acuta leaf against Staphylococcus aureus using evolutionary operation factorial design technique. International journal of molecular sciences, 12, 2395-2407.Makino, T., Furuta, Y., Wakushima, H., Fujii, H., Saito, K.i. & Kano, Y. (2003) Anti‐allergic effect of Perilla frutescens and its active constituents. Phytotherapy Research, 17, 240-243.Marder, K.S., Tang, M.X., Mejia-Santana, H. & et al. (2010) Predictors of parkin mutations in early-onset parkinson disease: The consortium on risk for early-onset parkinson disease study. Archives of Neurology, 67, 731-738.Ohlstein, B. & Spradling, A. (2006) The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature, 439, 470-474.Park, J., Lee, S.B., Lee, S., Kim, Y., Song, S., Kim, S., Bae, E., Kim, J., Shong, M. & Kim, J.-M. (2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature, 441, 1157-1161.Poddighe, S., Bhat, K.M., Setzu, M.D., Solla, P., Angioy, A.M., Marotta, R., Ruffilli, R., Marrosu, F. & Liscia, A. (2013) Impaired sense of smell in a Drosophila Parkinson`s model. PloS one, 8, e73156.Raudone, L., Burdulis, D., Raudonis, R., Janulis, V., Jankauskiene, L., Viskelis, P. & Trumbeckaite, S. (2016) EFFECT OF PERILLA FRUTESCENS EXTRACTS AND ROSMARINIC ACID ON RAT HEART MITOCHONDRIAL FUNCTIONS. Acta poloniae pharmaceutica, 73, 135-145.Samaranch, L., Lorenzo-Betancor, O., Arbelo, J.M., Ferrer, I., Lorenzo, E., Irigoyen, J., Pastor, M.A., Marrero, C., Isla, C., Herrera-Henriquez, J. & Pastor, P. (2010) PINK1-linked parkinsonism is associated with Lewy body pathology. Brain : a journal of neurology, 133, 1128-1142.Semchuk, K.M., Love, E.J. & Lee, R.G. (1992) Parkinson`s disease and exposure to agricultural work and pesticide chemicals. Neurology, 42, 1328-1335.Smeyne, R.J. & Jackson-Lewis, V. (2005) The MPTP model of Parkinson`s disease. Molecular Brain Research, 134, 57-66.Stefanis, L. (2012) α-Synuclein in Parkinson`s Disease. Cold Spring Harbor Perspectives in Medicine, 2, a009399.Ueda, H., Yamazaki, C. & Yamazaki, M. (2002) Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. Biological & pharmaceutical bulletin, 25, 1197-1202.Valente, E.M., Abou-Sleiman, P.M., Caputo, V., Muqit, M.M.K., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A.R., Healy, D.G., Albanese, A., Nussbaum, R., González-Maldonado, R., Deller, T., Salvi, S., Cortelli, P., Gilks, W.P., Latchman, D.S., Harvey, R.J., Dallapiccola, B., Auburger, G. & Wood, N.W. (2004) Hereditary Early-Onset Parkinson`s Disease Caused by Mutations in PINK1. Science (New York, N.Y.), 304, 1158-1160.van der Merwe, C., Jalali Sefid Dashti, Z., Christoffels, A., Loos, B. & Bardien, S. (2015) Evidence for a common biological pathway linking three Parkinson`s disease-causing genes: parkin, PINK1 and DJ-1. The European journal of neuroscience, 41, 1113-1125.伍永富, 秦少容 & 劉世琪 (2007) 紫蘇葉油的研究進展. 時珍國醫國藥, 18, 2019-2020. zh_TW
