蒼耳子化學成分及生物活性之研究

蒼耳 (Xanthium strumarium L.) 屬於菊科 (Compositae) 植物，分佈於歐亞與北美，在台灣全境低地，生長於河床、海岸及濕地。其種子可用來當作傳統中藥，可治療感冒、頭痛、鼻病、關節炎及具有降血糖的活性。基於對中國草藥所含生物活性成分之探討，我們選擇蒼耳，以其種子作為材料，探討其化學成分及其生物活性作用。從蒼耳子分離到二十八個化合物，包括三個thiazines：xanthiazone (1) ， xanthialdehyde (2) ， xanthiazone-?-D-glucoside (3)；一個thienocyclopyran：(8S)-(-)-xanthienopyran (4)；三個sesquiterpenes：xanthinosin (5) ， 11?,13-dihydroxanthinosin (6) ， xandiversifolide (7)；一個lactone：(2S,3R)-2,3-dihydroxy-2-methylbutyrolactone (8) ；一個lignan：pinoresinol (9)；一個neolignan：(7S,8R)-(+)-dihydrodehydroconiferyl alcohol (10) ；二個indoles：indole-3-carboxaldehyde (11) ， indole-3-carboxylic acid (12) ；十個benzenoids：2,4’-dihydroxydiphenylmethane (13) ， 4,4’-dihydroxydiphenylmethane (14) ， 3-methyl-4,4’-dihydroxydiphenylmethane (15) ， 2,4-bis(4-hydroxybenzyl)phenol (16) ， caffeic acid (17) ， methyl caffeate (18) ， coniferaldehyde (19) ， vanillin (20) ， vanillic acid (21) ， p-hydroxybenzaldehyde (22) ；四個steroids：?-sitosterol (23) 與 stigmasterol (24) 的混合物， ?-sitosteryl-?-D-glucoside (25) 與 stigmasteryl-?-D-glucoside (26) ；一個imide：succinimide (27) 及一個furan：5-(hydroxymethyl)furfural (28)。其中化合物2、3、4、6及7為新化合物； 8為首次從天然界分離得到； 9~16及27~28為第一次從蒼耳屬植物中分離得到；化合物13~16及27~28為第一次從菊科植物中分離得到；所有化合物均經由光譜及質譜分析加以證明。上述化合物在細胞毒殺活性研究方面，化合物1、3、4、8、11、14、20、23和24以及25和26人類鼻咽癌細胞 (HONE-1) 及胃癌細胞 (NUGC-3) 兩種癌細胞，在10 ?M、50 ?M和4 ?M、20 ?M濃度下，無明顯細胞毒殺效果。上述化合物在生物活性研究方面，化合物4具有良好的抗發炎活性，它對於fMLP/CB或PMA引起人類白血球產生的超氧自由基具有抑制效果。

關鍵字

蒼耳子；菊科；倍半萜抗發炎

並列摘要

Xanthium strumarium (Compositae) is distributed Eurasia and North America. In Taiwan, it grows in the river banks, seacoasts, and waste fields throughout the lowland. The seeds were used as a traditional Chinese medicine for common cold, headache, nasal discharge, arthritis and exhibited the action of lowing blood sugars. As a part of our research on the biologically active components from Chinese medicinal plants, the seeds of X. strumarium were chosen to be investigated. Twenty-eight compounds, including three thiazines : xanthiazone (1), xanthialdehyde (2), xanthiazone-?-D-glucoside (3), one thienocyclopyran : (8S)-(-)-xanthienopyran (4), three sesquiterpenes : xanthinosin (5), 11?,13-dihydroxanthinosin (6), xandiversifolide (7), one lactone : (2S,3R)-2,3-dihydroxy-2-methylbutyrolactone (8), one lignan : pinoresinol (9), one neolignan : (7S,8R)-(+)-dihydrodehydroconiferyl alcohol (10), two indoles : indole-3-carboxaldehyde (11), indole-3-carboxylic acid (12), ten benzenoids : 2,4’-dihydroxydiphenylmethane (13), 4,4’-dihydroxydiphenylmethane (14), 3-methyl-4,4’-dihydroxydiphenylmethane (15), 2,4-bis(4-hydroxybenzyl)phenol (16), caffeic acid (17), methyl caffeate (18), coniferaldehyde (19), vanillin (20), vanillic acid (21), p-hydroxybenzaldehyde (22), four steroids : a mixture of ?-sitosterol (23) and stigmasterol (24), ?-sitosteryl-?-D-glucoside (25) and stigmasteryl-?-D-glucoside (26), one imide : succinimide (27), one furan : 5-(hydroxymethyl)furfural (28), were obtained from the seeds. The structures of all isolated compounds were elucidated by modern spectral and mass analyses. Among them, 2, 3, 4, 6 and 7 are new compounds. Compound 8 is isolated from natural source first time. Compounds 9~16 and 27~28 are isolated from genus Xanthium for the first time. Compounds 13~16 and 27~28 are isolated from family Compositae for the first time. Componds 1, 3, 4, 8, 11, 14, 20, 23 and 24, 25 and 26 showed unapparent cytotoxicity against HONE-1 (human nasopharyngeal carcinoma) and NUGC-3 (human gastric cancer) cell lines at concentration of 10 μM, 50 μM and 4 μM, 20 μM respectively. Compound 4 showed significant antiinflammatory activity. It exhibits inhibitory effects on superoxide anion generation by human neutrophils in response to fMLP/CB or PMA.