蘭嶼木耳菜與黃花三七草化學成分及抗血小板凝集活性之研究暨台灣產三七草屬植物肝臟毒性之評估

摘要　　由四種具抗血小板凝集活性之三七草屬植物選擇黃花三七草及蘭嶼木耳菜進行生物活性成分之分離。由黃花三七草（Gynura japonica）的根莖部，共鑑定出75個化合物，其中包含10個新化合物： (—)-α-tocospirone、(—)-trans-gynuraone、(22E,24S)-7α-hydroperoxystigmasta-5,22-dien-3β-ol、(22E,24S)-stigmasta-1,4,22-trien-3-one、(24R)-stigmasta-1,4-dien-3-one、3-O-?-D-glucopyranosyl (22E,24S)-3β-hydroxystigmasta-5,22-dien-6-one及gynuramide I~IV。而由蘭嶼木耳菜（G. elliptica）根部迄今共得到27化合物，其中包含3個新化合物：(—)-trans-gynuraone、(+)-gynunone及(—)-gynunol。　　於抗血小板凝集實驗結果，初步發現pyrrolizidine生物鹼並不具有抗血小板凝集活性，而生物活性導引分離發現抗血小板凝集活性主要來自phenylalkanoid、chromanone derivative、caryophyllane及1,4-benzoquinone類的成分，其中又以2,6-dimethoxy-1,4-benzoquinone的抗血小板凝集活性最強。其他活性成分則包括：6-acetyl-2,2-dimethylchroman-4-one、vanillin、benzoic acid、caryophyllene oxide等成分。此外，由於(22E,24S)-7α-hydroperoxystigmasta-5,22-dien-3β-ol及(24R)-7α-hydroperoxy- stigmasta-5-en-3β-ol具有hydroperoxyl 官能基，因而具有使血小板凝集之效果。而促凝血之專利化合物：3-O-?-D-glucopyranosyl (24R)-3β-hydroxystigmasta-5-en-6-one 及3-O-?-D-glucopyranosyl (22E,24S)- 3β-hydroxystigmasta-5,22-dien-6-one亦於黃花三七草中獲得。　　在肝臟毒性的評估方面，地上部的實驗結果發現以紅鳳菜（G. bicolor）呈現出最強的致肝毒性，而地下部份的實驗結果則以蘭嶼木耳菜呈現出最強的致肝毒性，但生物鹼含量最多的蘭嶼木耳菜根部，其致肝毒性反而遠不及沒有生物鹼的紅鳳菜地上部，故推測導致肝臟毒性之化合物除傳統上認定之吡咯連啶生物鹼外，其他非生物鹼化合物也扮演了部分肝毒性角色。

關鍵字

蘭嶼木耳菜；黃花三七草；土三七；三七草屬；根莖；吡咯連啶生物鹼；肝臟毒性；抗血小板凝集

並列摘要

Abstract 　　Gynura japonica and Gynura elliptica were selected for bioactive principles isolation from 4 species of Genera Gynura with anti-platelet aggregation effect. 75 compounds were isolated from the rhizome of Gynura japonica. Of the all isolates, 10 compounds are new, viz., (—)-α-tocospirone, (—)-trans-gynuraone, (22E,24S)-7α- hydroperoxy-stigmasta-5,22-dien-3β-ol, (22E,24S)-stigmasta-1,4,22-trien-3-one, (24R)-stigmasta-1,4-dien-3-one, 3-O-?-D-glucopyranosyl (22E,24S)-3β-hydroxy- stigmasta-5,22-dien-6-one and gynuramide I~IV. 27 compounds were isolated from the root of G. elliptica. Among the all isolates, 3 are new, viz., (—)-trans-gynuraone, (+)-gynunone and (—)-gynunol. 　　From anti-platelet aggregation screen, pyrrolizidine alkaloids did not possess anti-platelet aggregation activity. Bioassay-guided fractionation has led to the isolation of phenylalkanoid, chromanone derivative, caryophyllane and 1,4-benzoquinone as active principles. From the all isolates, 2,6-dimethoxy-1,4-benzoquinone was the most potent ones against platelet aggregation. 6-Acetyl-2,2-dimethylchroman-4-one, vanillin, benzoic acid and caryophyllene oxide are also active constituents. Furthermore, (22E, 24S)-7α-hydroperoxystigmasta-5,22-dien-3β-ol and (24R)-7α-hydroperoxystigmasta- 5-en-3β-ol with hydroperoxyl moiety could induce platelet aggregation spontaneously. Compound 3-O-?-D-glucopyranosyl (24R)-3β-hydroxystigmasta-5-en-6-one and 3-O-?-D-glucopyranosyl (22E,24S)-3β-hydroxystigmasta-5,22-dien-6-one with patent on haemostatic and capillary stabilizing effect were also obtained from G. japonica. 　　Comparing on the aerial part, G. bicolor showed the most potent hepatotoxicity. On the other side, G. elliptica showed the most potent toxicity in the underground part screen. The underground part of G. elliptica where pyrrolizidine alkaloids were the most abundant showed less hepatotoxicity then the non-alkaloidal aerial part of G. bicolor. This observation indicated that all the hepetotoxicity of the plant might be not only due to pyrrolizidine alkaloids. Other non-alkaloidal constituents may also play an important role in the hepatotoxicity of Gynura plants.