臺灣博碩士論文加值系統

在台灣「一條根」之同名異物藥材雜多，其來源可追溯計分屬於5科12屬19種的不同植物。本研究主要針對目前市售品中較為主流的4種「千斤拔屬」、2種「大豆屬」以及僅產於金門的「蠅子草屬」女婁菜等7種「一條根」，進行藥學相關的文獻考察、市售調查、顯微及分子生物學鑑定、特定藥理活性成分含量比較、藥理試驗研究，並對金門特產的闊葉大豆（習稱：金門一條根）進行保健功能及安全性評估研究。
從本研究中發現目前市售的一條根類藥材在台、澎地區以「蔓性千斤拔」為主，係傳統的一條根，做為民間藥，使用歷史最久。該植物在本土野生或栽培之數量現極為稀少，評估其醫療保健效能及可開發性優良，值得於國內加以復育，並在成分藥理學上更進一步繼續深入探討。
金門市售的一條根以「闊葉大豆」根部藥材為主，該植物為一種野生大豆，現經該縣農試所推廣栽培以及業者開發系列性保健產品，已發展成為該地區特有的一項產業。
在本研究之各項試驗中，生藥組織學顯微鑑別及DNA定序鑑別研究的結果，能清楚地將各種一條根類藥材比較並區分。
針對不同一條根類藥材所可能含有daidzin、daidzein、genistin、genistein四個異黃酮成分的含量，利用HPLC的方法進行比較分析，結果顯示各同名異物藥材中異黃酮類成分含量差異甚大。其中genistein的含量以球穗花千斤拔最高，達2.29 μg/g； genistin的含量以大葉千斤拔最，達1.29 μg/g。
從各種不同致發炎劑所誘發的抗炎試驗中發現闊葉大豆的抗發炎作用與傳統一條根的千斤拔頗相似。比較台灣產4種千斤拔屬植物根部的抗發炎試驗結果發現蔓性千斤拔及球穗花千斤拔的抑制作用較強。
在抗過敏試驗中發現該4種千斤拔及闊葉大豆皆能明顯地抑制第四型過敏反應，當中又以球穗花千斤拔根部50％乙醇粗萃取物的作用最強。另也發現大葉千斤拔亦能抑制第三型過敏反應。
探討金門才有的女婁菜根部50％乙醇粗萃取物對肝損傷改善作用的試驗結果顯示其能明顯防止CCl4及acetaminophen給藥所造成化學性肝損傷的進展。
針對闊葉大豆根部水粗萃取物(AGT)保健功能評估所進行的各項試驗，發現其對高血脂倉鼠，能降低其總膽固醇、低密度脂蛋白，增加高密度脂蛋白，顯示其對高脂血症有一定的改善作用。對腸胃功能影響的動物試驗中，也發現其在餵食28天後，能明顯增加腸道內益生性乳酸桿菌的數目，此有可能係由於其成分中含有益菌之益生物質如寡糖等。此外，AGT能增加腸道的消化酵素及glutathione之活性，促進胃腸蠕動，卻不影響胃酸分泌的作用，顯示其對胃腸功能具有一定的改善效能。AGT的保肝功能試驗結果則發現其對化學性肝損傷未具改善作用。
AGT所進行的各項安全性評估試驗，顯示其對大鼠的急性毒性大於10g/kg（相當於生藥乾品80g/kg）。28天餵食毒性試驗及 90天餵食毒性試驗的結果顯示其安全劑量宜在1.7 g/kg（相當於生藥乾品15.45 g/kg）以下。致畸試驗中未見AGT有引起致畸胎之作用；以Amest test及鼷鼠骨髓細胞之微核測試法來評估AGT的基因毒性，其結果均顯示AGT並無致突變作用。
本研究針對國內同名異物混雜的一條根類藥材進行系列性的評估及研究，期望這些試驗的結果能提供學術界和醫藥、保健產品、生物技術產業界及農政、藥政等主管單位在後續對一條根進行評估、研究及開發上作為有益之參考。

Like other Traditional Chinese Materia Medica, numerous homonymic commercial I-Tiao-Ken (ITKs) were frequently found in the herbal market of Taiwan. These ITKs were identified to be originated from plant roots of 19 different species of 12 genera in 5 families.
In this study, 7 major ITKs of genus Flemingia (4s), Glycine (2s) and Silene (1s) were initially targeted and investigated through literature review, market survey, comparative anatomical and molecular biological identification, comparative analysis on certain active components as well as several pharmacological experiments. In addition, Glycine tomentella HAYATA (a wild soybean, as also called: Kinmen ITK), a unique drug material of ITK from Kinmen Area was extraordinarily studied for its effectiveness on health care and safety in this study.
From the market investigation, the traditional and the early-used ITK -Flemingia prostrata ROXB. was found to be the major commercial item of ITKs in Taiwan and Penghu Islands (Pescadores Islands ).
At present, the indigenous quantity or plantation of F. prostrata is found scarce locally. Considering its fine efficacy and potential for health care, it is therefore suggested worthily to cultivate and propagate as well as to investigate its ingredients and pharmacological effects .
On the contrary, the most popular ITK commercially available in Kinmen is G. tomentella, the wild soybean. The plant is now mostly cultivated by farmers with promotion and contracting from the local County Agricultural Research Institute. A series of health products made from this herb have been developed by many stores and business companies on the islet, and a very unique industry relied on this medicinal plant has been also established locally.
In this study, difference between several ITKs were compared and distinguished by pharmacognostical microscopic and DNA sequencing identification methods.
We also analysed the content of isoflavones such as daidzin, daidzein, genistin and genistein in ITKs. Results from the comparative quantitative analysis by HPLC showed that these 4 isoflavones in the homonymic ITKs differ greatly, the largest content of genistein (2.29μg/g) was found in Flemingia strobilifera (L.) R. BR. & AIT., while the largest content of genistin (1.29μg/g) was found in F. macrophylla (WILLD.) MERR.
In the anti-inflammatory experiments caused by various inflammation inducers, the effect of G. tomentella was found similar to that of F. prostrata. Compared the 4 ITKs originated from 4 species of Flemingia genus grown in Taiwan, F. prostrata and F. strobilifera showed stronger anti-inflammatory effects than others.
In the anti-allergic experiment, all the 50% ethanolic crude extracts of ITKs of 4 Flemingia and G. tomentella showed obvious inhibitory effects to Type IV hypersensitivity, F. strobilifera was found to be the strongest in these 5 ITKs. F. macrophylla was found effective to inhibit Type III hypersensitivity also.
We also investigated the ameliorative effect of the 50% ethanolic crude extract of the root of Silene aprica TURCZ. (a plant indigenous only to Kinmen) on liver injuries induced by chemicals. Results indicated that it prevented the progress of liver damage caused by CCl4 and acetaminophen.
The aqueous crude extract of the root of G. tomentella (AGT) showed its cholesterol and low density lipoprotein lowering and high density lipoprotein elevating effects. These results suggested that it may exhibit ameliorative effect for the treatment of hyperlipidemia.
In the animal study of the effect on gastrointestinal function of AGT, it was found that after administration of AGT for 28 days, flora of probiotical Lactobacillus was increased significantly. This was proposed to be caused by some prebiotics, such as oligosaccharides in the root of G. tomentella.
Besides that, AGT also showed to increase the activities of intestinal enzymes and glutathione and enhance gastrointestinal motility but did not affect the gastric secretion. These results suggested that it had certain ameliorative effect to the gastrointestinal function.
In the animal study of liver protective function of AGT. AGT showed no ameliorative effect to the chemical-induced liver damage.
The LD50 of AGT in rats was found larger than 10g/kg (equivalent to 80 g/kg of crude drug) on acute toxicity test. Safety dose of 1.7 g/kg (equivalent to 15.45 g/kg of crude drug) was proposed after chronic toxicity tests of 28 days and 90 days administration. No teratogenicity and mutagenicity was found in the teratogenetic test and in the genetic toxicity studies of Ames test and micronucles test.
This study was focused on evaluation and investigation to the complex homonymic crude drug of ITKs in Taiwan. Results of this study are highly expected to be useful and beneficial for any academia, industries of medical, health care, biotechnologies and relative agricultural, health authorities, in the occasion of their further evaluation, research and development on ITKs.

表目錄………………………………………………………………....i
圖目錄………………………………………………………………..iii
略字表……………………………………………………………….vii
中文摘要……………………………………………………………...x
英文摘要…………………………………………………………....xiii
第一章 緒言………………………………………………………...1
第二章 總論………………………………………………………...5
第一節 研究之動機及背景………………………………………………..5
第二節 一條根類藥材之淵源……………………………………………10
第三節 研究方向及內容…………………………………………………28
第四節 豆科千斤拔屬一條根類藥材之文獻考察………………………30
壹、 千斤拔屬植物之藥用植物學文獻考察………………………30
貳、 千斤拔屬植物之藥材學文獻考察……………………………33
參、 千斤拔屬植物之生藥學文獻考察……………………………43
肆、 千斤拔屬植物之植物化學成分文獻考察……………………44
伍、 千斤拔屬植物之藥理學文獻考察……………………………46
第五節 豆科大豆屬一條根類藥材之考察………………………………53
壹、 大豆屬植物之藥用植物學文獻考察…………………………54
貳、 大豆屬植物之藥材學文獻考察………………………………56
參、 大豆屬植物之生藥學文獻考察………………………………58
肆、 大豆屬植物之植物化學成分文獻考察………………………58
伍、 大豆屬植物之藥理學文獻考察………………………………59
第六節 一條根類藥材之來源及臨床應用考察…………………………65
壹、 市售各種一條根藥材來源之調查……………………………65
貳、 一條根藥材之民間驗方及應用調查…………………………71
第三章 試驗材料與方法………………………………………….84
第一節 一條根類藥材之鑑別研究……………………………………....84
壹、 一條根類藥材之顯微鑑別…………………………………....84
貳、 一條根類藥材之DNA定序鑑別……………………………..88
第二節 一條根類藥材中異黃酮含量之比較研究……………………....92
第三節 一條根類藥材之藥理研究………………………………………95
壹、 闊葉大豆根部抗氧化作用之研究……………………………95
貳、 一條根類藥材抗發炎作用之研究……………………………98
參、 一條根類藥材抗過敏作用之研究……………………………99
肆、 球穗花千斤拔根部在遲發型過敏反應中對淋巴細胞
次族群調節作用之研究……………………………………..100
伍、 女婁菜根部抗氧化作用之研究……………………………..102
陸、 女婁菜根部對四氯化碳及乙醯胺基酚引起大鼠肝損傷
改善作用之研究……………………………………………..103
第四節 闊葉大豆根部保健功能之評估研究…………………………..106
壹、 闊葉大豆根部降血脂作用之研究…………………………..106
貳、 闊葉大豆根部對胃腸功能改善作用之研究………………..107
參、 闊葉大豆根部護肝功能之研究……………………………..111
第五節 闊葉大豆根部安全性評估之研究……………………………..114
壹、 闊葉大豆根部對大鼠急性及28天餵食毒性試驗…………114
貳、 闊葉大豆根部對大鼠90天餵食毒性試驗…………………116
參、 闊葉大豆根部致畸試驗……………………………………..117
肆、 闊葉大豆根部初步基因毒性試驗………………………......118
第四章 試驗結果………………………………………………...121
第一節 一條根類藥材之鑑別研究……………………………………..121
壹、 一條根類藥材之顯微鑑別…………………………………..121
貳、 一條根類藥材之DNA定序鑑別…………………………...137
第二節 一條根類藥材中異黃酮含量之比較研究……………………..148
第三節 一條根類藥材之藥理研究……………………………………..154
壹、 闊葉大豆根部抗氧化作用之研究…………………………..154
貳、 一條根類藥材抗發炎作用之研究…………………………..159
參、 一條根類藥材抗過敏作用之研究…………………………..169
肆、 球穗花千斤拔根部在遲發型過敏反應中對淋巴細胞
次族群調節作用之研究……………………………………..180
伍、 女婁菜根部抗氧化作用之研究……………………………..182
陸、 女婁菜根部對四氯化碳及乙醯胺基酚引起大鼠肝損傷
改善作用之研究……………………………………………..182
第四節 闊葉大豆根部保健功能之評估研究…………………………..189
壹、 闊葉大豆根部降血脂作用之研究…………………………..189
貳、 闊葉大豆根部對胃腸功能改善作用之研究………………..194
參、 闊葉大豆根部護肝功能之研究……………………………..201
第五節 闊葉大豆根部安全性評估之研究……………………………..211
壹、 闊葉大豆根部對大鼠急性及28天餵食毒性試驗…………211
貳、 闊葉大豆根部對大鼠90天餵食毒性試驗……………........220
參、 闊葉大豆根部致畸試驗……………………………………..229
肆、 闊葉大豆根部初步基因毒性試驗…………………………..232
第五章 試驗討論………………………………………………...234
第一節 一條根類藥材之鑑別研究……………………………………..234
壹、 一條根類藥材之顯微鑑別…………………………………..234
貳、 一條根類藥材之DNA定序鑑別…………………………....236
第二節 一條根類藥材中異黃酮含量之比較研究……………………..241
第三節 一條根類藥材之藥理研究……………………………………..244
壹、 闊葉大豆根部抗氧化作用之研究…………………………..244
貳、 一條根類藥材抗發炎作用之研究…………………………..247
參、 一條根類藥材抗過敏作用之研究…………………………..250
肆、 球穗花千斤拔根部在遲發型過敏反應中對淋巴細胞
次族群調節作用之研究……………………………………..253
伍、 女婁菜根部抗氧化作用之研究……………………………..256
陸、 女婁菜根部對四氯化碳及乙醯胺基酚引起大鼠肝損傷
改善作用之研究……………………………………………..257
第四節 闊葉大豆根部保健功能之評估研究…………………………..260
壹、 闊葉大豆根部降血脂作用之研究…………………………..260
貳、 闊葉大豆根部對胃腸功能改善作用之研究………………..261
參、 闊葉大豆根部護肝功能之研究……………………………..263
第五節 闊葉大豆根部安全性評估之研究……………………………..267
壹、 闊葉大豆根部對大鼠急性及28天餵食毒性試驗…………267
貳、 闊葉大豆根部對大鼠90天餵食毒性試驗…………………269
參、 闊葉大豆根部致畸試驗……………………………………..269
肆、 闊葉大豆根部初步基因毒性試驗…………………………..271
第六章 結論……………………………………………………...273
參考文獻…………………………………………………………...279
研究業績…………………………………………………………...293

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