臺灣產刀傷草(Ixeris laevigata SCHULTZ-BIP. var. oldhami KITAMURA)及崗脂麻(Helicteres angustifolia LINNAEUS)之化學成分與藥理活性評估; Evaluation of the Chemical Constituents and the Pharmacological Activities of Ixeris laevigata SCHULTZ-BIP. var. oldhami KITAMURA and Helicteres angustifolia LINNAEUS from Taiwan

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Title:	臺灣產刀傷草(Ixeris laevigata SCHULTZ-BIP. var. oldhami KITAMURA)及崗脂麻(Helicteres angustifolia LINNAEUS)之化學成分與藥理活性評估;Evaluation of the Chemical Constituents and the Pharmacological Activities of Ixeris laevigata SCHULTZ-BIP. var. oldhami KITAMURA and Helicteres angustifolia LINNAEUS from Taiwan
Authors:	盧國樑;Kuo-Liang Lu
Contributors:	中國醫藥學院中國藥學研究所
Keywords:	刀傷草;Ixeris laevigata
Date:	1999
Issue Date:	2009-11-26 12:00:05 (UTC+8)
Abstract:	摘要刀傷草（Ixeris laevigata SCHULTZ-BIP. var. oldhami KITAMURA）為菊科苦?菜屬（Ixeris）植物，在臺灣地區常被當蒲公英來代用。本研究經由對菊科苦?菜屬植物之藥用植物學、生藥學、成分與藥理學等各項之文獻考察與整理，提供做本屬植物之後續研究參考。並對刀傷草之根、莖及葉進行組織切片研究，建立生藥學研究之鑑定依據。在化學研究上，針對過去所分離得到之四種黃酮類 (luteolin, luteolin-7-O-glucoside, apigenin, apigenin-7-O-glucoside)及兩種香豆素類(esculetin, esculin)等六種指標成分，建立刀傷草之高效液相層析之良好分析條件。並應用於刀傷草檢品之萃取條件之探討或藥材鑑別之另種依據，亦可供做市場品之品質評估方法。抗發炎及抗過敏試驗方面，刀傷草粗抽物及其二氯甲烷層及乙酸乙酯分配萃取層，對fMLP誘發嗜中性白血球的去顆粒作用所釋出b-glucuronidase及lysozyme具抑制作用，顯示其抗發炎活性。其中以?元成分luteolin、apigenin及esculetin顯示強而顯著之抑制作用，為刀傷草中抗發炎作用之主要活性成分。對fMLP誘發嗜中性白血球的超氧自由基形成具抑制作用優於PMA所誘發者，且其抗發炎作用主要在周邊細胞。刀傷草之保肝作用的探討，以四氯化碳(CCl4)、半乳糖氨(D-galactosamine，D-GalN)、a-?異硫氰酸酯(a-naphthylisothiocyanate，ANIT)誘發大白鼠不同肝損傷，或以酒精(alcohol，EtOH)及乙醯酚胺(acetaminophen，APAP) 誘發大白鼠肝(腎)損傷進行刀傷草對各療法之保肝活性及療效評估。刀傷草對這幾種化學性肝傷害皆有不等程度的緩和效果。顯見其作用並非由單一之機轉所達成，可能是經由數種作用機轉之綜合。抗氧化作用在此扮演著重要的角色。其黃酮類成分apigenin、luteolin，香豆素成分esculetin及其帶糖?都可能是保肝作用之活性成分。崗脂麻（Helicteres angustifolia LINNAEUS）為梧桐科（Sterculiaceae）山芝麻屬（Helicteres）植物，在臺灣地區常被當山豆根來代用。經由對梧桐科山芝麻屬植物之藥用植物學、生藥學、成分與藥理學等各項之文獻考察與整理，供做本屬植物之後續研究參考。並對崗脂麻之根及莖進行組織切片研究，建立生藥學研究之鑑定依據。在成分研究方面，從崗脂麻根分離得到betulin（1）, betulinic acid（2）, betulinic acid methyl ester（3）, b-sitosterol（4）, oleanolic acid（5）, 3b-acetoxy-27-benzoyloxylup -20(29)en-28-oic acid methyl ester (methyl helicterate)（6）, 3b-acetoxy-27-benzoyloxylup-20(29)en-28-oic acid（7）, 3b-acetoxy-27-(p-hydroxyl)-benzoyloxylup-20(29)en-28-oic acid methyl ester（8） and 3-(E)-coumaroyl-betulinic acid（9）等三?類為主之化合物。並對其中化合物6, 7, 8等三種指標成分建立高效液相層析之良好分析條件。應用於崗脂麻檢品萃取條件之探討，發現在甲醇為溶劑時，顯示最佳之抽出率。在市售藥材之評估比較中，著者發現三指標成分主要存在於根皮部，而於木質部幾乎無法檢測到其存在，且根部的長成粗細與三指標成分含量有關。崗脂麻根之甲醇粗抽物對小鼠口服給藥之半致死劑量（LD50）為2.54 g/kg，顯示其毒性，在使用上宜多注意。崗脂麻根之甲醇粗抽物及各有機溶媒萃取層對A-549，HT-29，KB-16及P-388等四種癌細胞之體外試驗均有明顯抑制作用，其中乙酸乙酯萃取層對HT-29之ED50為0.581 mg/ml最強。然所分離得到之9個化合物，對四種癌細胞均未顯示其抗癌活性。在抗發炎活性方面，乙酸乙酯層及正丁醇層對fMLP誘發嗜中性白血球的去顆粒作用所釋出b-glucuronidase之釋出具顯著抑制作用，其IC50分別為16.7及56.3 mg/ml。並對lysozyme之釋出亦具有顯著抑制作用，故可確認崗脂麻之抗發炎活性。; Abstract Ixeris laevigata SCHULTZ-BIP. var. oldhami KITAMURA, of Compositae family, is a folk medicine commonly used in Taiwan. It is often substituted for Pwu-Gong-Ing (Taraxaci Herba) on the Taiwan market. This study was first based on the investigations and literature survey of pharmacobotany, pharmacognosy, phytochemistry and pharmacology of Ixeris genus. We hope to provide some information for the subsequent research. The present studies show the pharmacognostical anatomy of the root, stem and leaf of I. laevigata var. oldhami for identification. To evaluate the quality of I. laevigata var. oldhami, a simple, rapid, and accurate high-performance liquid chromatographic (HPLC) method was developed for the assay of four flavonoids: apigenin, apigenin-7-O-glucoside, luteolin and luteolin-7-O-glucoside, and two coumarins, esculetin and esculin, which we isolated from this plant previously. It was helpful for both identification of medicinal herbs and the extraction solvent choice in the evaluation of market crude samples. This study also compares their constituents with those of similar folk herbs, I. chinensis and Taraxacum formosanum, commonly used as an adulterant by their HPLC chromatograms. The pharmacological study showed that the crude methanol extract and its fractions partitioned by n-hexane, dichloromethane, ethyl acetate and n-butanol exhibited parallel effects against the release of b-glucuronidase and lysozyme on neutrophil degranulation induced by fMLP. Among them, the dichloromethane and the ethyl acetate fractions showed the best anti-inflammatory effect. The aglycone constituents, luteolin, apigenin and esculetin which are the major active components for the anti-inflammatory effect, showed strong and significant inhibitory effects. The results also revealed that the inhibitory activity of flavonoids and coumarins against the neutrophil superoxide formation induced by fMLP is better than that induced by PMA. The accu
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