京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第17792号 / 農博第2013号 / 新制||農||1016(附属図書館) / 学位論文||H25||N4783(農学部図書室) / 30599 / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 阪井 康能, 教授 小川 順, 教授 梅澤 俊明 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

Perilla L. are significant for multi-pharmacological effect. The aim of this work is to study Perilla L. growth and develop¬ment tendencies, productivity; composition of biologically active compounds and their variations during the vegetation period, and the biological effect of the extracts; to select perspective plants for cultivation in Lithuania and for production of medicinal preparations. The objectives of the Study: To investigate and determine growth dynamics of Perilla L. species and varieties during the vegetation period and to assess the influence of climate conditions on the vegetation rhythmic. To assess the quantity dynamics of Perilla L. species and varieties herbal medicinal raw material and to compare the productivity of Perilla L. species and varieties. To determine the quantity of the essential oil in Perilla L. species and varieties and to identify the chemotypes of the plants. To determine the qualitative composition and variation dynamics of the phenolic acids in Perilla L. species and varieties. To determine the composition and variation dynamics of the flavone complex in Perilla L. species and varieties. To determine the composition and variation dynamics of antho¬cyanidines in Perilla L. species and varieties. To assess the radical scavenging activity of the extracts of Perilla L. species and varieties raw materials. To research the effect of Perilla L. extracts on the oxidative phosphorylation in the rat heart mitochondria. / Perilla L. genties vienmečiai vaistiniai augalai yra augaliniai imunomoduliatoriai, pasižymintys daugeliu farmakologinių poveikių. Darbo tikslas: Ištirti Vidurio Lietuvoje auginamų Perilla L. rūšių ir varietetų augimo ir vystymosi dėsningumus, biologiškai aktyvių junginių sudėtį ir jų įvai¬ravimą vegetacijos metu bei ekstraktų biologinį poveikį; atrinkti perspek¬tyvius augalus auginimui Lietuvoje. Uždaviniai: Ištirti ir nustatyti Perilla L. augimo dinamiką vegetacijos metu ir įvertinti klimatinių veiksnių įtaką augalų vegetacijai. Įvertinti Perilla L. vaistinės augalinės žaliavos kiekio dinamiką vege¬tacijos metu ir palyginti Perilla L. rūšių ir varietetų produk¬tyvumą. Nustatyti Perilla L. rūšių ir varietetų eterinio aliejaus kiekį auga¬luose vegetacijos metu ir identifikuoti augalų chemotipus. Nustatyti Perilla L. rūšių ir varietetų fenolinių rūgščių kokybinę sudėtį ir jų kitimo dėsningumus vegetacijos metu. Nustatyti Perilla L. rūšių ir varietetų flavonų komplekso sudėtį ir kitimo dinamiką vegetacijos metu. Nustatyti Perilla L. rūšių ir varietetų antocianidinų sudėtį bei kitimo dinamiką vegetacijos metu. Įvertinti Perilla L. rūšių ir varietetų žaliavų ekstraktų antiradikalinį aktyvumą. Ištirti Perilla L. rūšių ir varietetų ekstraktų poveikį žiurkės širdies mitochondrijų oksidaciniam fosforilinimui. Tyrimų rezultatai ir poveikiu pasižyminčių junginių identifikavimas atveria perspektyvas ateities tyrimams, kurie reikalingi kuriant preparatus iš perilių augalinių žaliavų.

1. INTRODUCTION The incidence of diseases whose pathogenesis chain includes changes in the functioning of the immune system is currently on the increase. The increasing prevalence of primary and secondary immunodeficiencies is a relevant issue in immunopathology. Secondary immunodeficiencies, caused by such factors as bacteria, viruses, helminths, chemical substances, medications, radiation, stress, etc., result in higher morbidity. Immunosuppression occurs in cases of oncological or allergic diseases, bronchial asthma, etc. immunosuppression is relevant in cases of malignant tumors whose incidence in Lithuania has been increasing with every year during the recent period. Oncological treatment involves the application of radiotherapy and chemotherapy with cytostatics that are strong immunosuppressants, and thus the restoration of the immune system with immunostimulants is becoming a relevant issue. Insufficient nutrition, disturbed nutrient resorption, negative nitrogen balance, chronic alcoholism, and drug abuse – all these factors result in the deceleration of cell proliferation and decreased T-lymphocyte counts and function. Immunodeficiency increases morbidity with infectious diseases, since the organism becomes incapable of the rapid destruction of the causative agents. Such conditions increase the probability of the spreading of the infection, and condition the increased activity of the opportunistic infections caused by adenoviruses, cytomegaloviruses, etc... [to full text]

The results of the investigation of Perilla frutescens (L.) Britton growth, vegetation rhythmic dependence upon meteorological factors is given here. Experiments were carried out in 2001 – 2005 during vegetation period at Kaunas Botanical Garden of Vytautas Magnus University. Object of investigations - Perilla frutescens (L.) Britton a medicinal, herbal immunomodulator, annual herbaceous deadnettle family (Lamiaceae Lindl.) plant originated from Asia passes all development cycle in middle Lithuanian climatic conditions. P. Frutescens vegetation length on the average is 167 days. Earliest initiation of vegetation and optimal climatic conditions for growth are when HTC=1,60-1,80, that is excess heavy humidity. Optimal climatic conditions for massive flowering and seed ripeness are when HTC=1,20, then massive flowering starts 10 days earlier and Lasts for 25 days. Strong correlation interdependence was established between massive flowering and HTC (R2=0,9406). After the investigation of P.frutescens terraneous parts (high, relative plain area) consistent patterns of vegetation rhythmic, the optimal harvest time, which determines raw material’s quality and quantity, was established, by using mathematical – statistical methods.

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.

京都大学 / 新制・課程博士 / 博士(薬科学) / 甲第23133号 / 薬科博第132号 / 新制||薬科||14(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 中山 和久, 教授 二木 史朗, 准教授 伊藤 美千穂 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM