關木通化學成分及其生物活性之研究

中文摘要關木通（Aristolochia manshuriensis）是一種多年生灌木植物，並分布在中國東北及韓國。馬兜鈴屬的植物在中醫藥使用上，被用於抗菌、抗發炎和平喘劑的功能，在先前的研究發現馬兜鈴酸是馬兜鈴屬植物最主要的成分並且長期使用下會有腎毒性和致癌的風險。關木通莖部在室溫下以甲醇連續抽取，其抽取液經減壓濃縮後得甲醇粗萃物。甲醇粗萃物再以二氯甲烷溶液(CH2Cl2) 和水(H2O)分配萃取，分別收集二氯甲烷溶液層及水層；水層則以正丁醇層(n-Butanol)和水層(H2O)進行再進行分配萃取，將二氯甲烷溶液層經減壓濃縮後以Celite為管柱填充物進行管柱層析，配製四種不同極性的溶液系統進行沖堤分別得到正己烷層(n-Hexane)、正己烷與乙酸乙酯(Ethyl acetate) (1:1)層、乙酸乙酯層和甲醇層(MeOH)，共得到六層。經抗發炎活性篩選得知，正己烷層、正己烷與乙酸乙酯(1:1)層、乙酸乙酯層和甲醇層具有由fMLP/CB 所誘導抑制人類嗜中性白血球之superoxide anion生成和elastase釋放的活性。將正己烷層、正己烷與乙酸乙酯(1:1)層、乙酸乙酯層和甲醇層經由管柱層析和高效能液相層析分析儀進行化學成分分離與純化，共得到本研究結果共從關木通分離純化得到二十五個化合物，分別為四個aristolochic acids︰ aristolochic acid I (4)、aristolochic acid-IIIa (7)、aristolochic acid-IV a(6)、aristolochic acid II (5)，一個sodium salt of aristolochic acids︰sodium aristolochate I (21)，五個 aristolactams ︰aristolatams IIIa (8)、aristolactam III (11)、aristolactam I (9)、aristolactam II (12)、aristolactam Ia (10) ，三個denitroaristolochic acids ︰aristolamide (2)、aristolamide II (3)、demethylaristofolin E (16)，五個aristolochic acid alkyl esters ︰aristolic acid methyl ester (17)、6-methoxyaristolic acid methyl ester (18)、aristolochic acid-I methyl ester (13)、aristolochic acid-IV methyl ester (14)、aristolochic acid IVa methyl ester (15)，二個amides︰ N-trans-feruloylmethoxytyramine (19)、aristopyridinone A (25)，一個benzenoid︰ trans-p-coumaric acid (20)，四個steroid︰??-sitosteryl-3-O-??-D-glucoside & stigmasteryl-3-O-??-D-glucoside (22)、β-stigmasterol (23)、6β-hydroxystigmast-4-en-3-one (24)、β-sitosterone (25)。其中，化合物1為新骨架之新化合物，化合物 3 為新化合物，所分離得之所有化合物都經由光譜及質譜等分析方法加以證明。在抗發炎活性測試中，化合物8對於superoxide anion generation具有很強的抑制活性，且對於elastase release具有很顯著的抑制活性，化合物3對於 elastase release具有中度的抑制活性。

關鍵字

關木通

並列摘要

Abstract Aristolochia manshuriensis (Guanmuton) (Aristolochiaceae) is a perennial shrub plant, and distributed in the northeastern of the China and Korea. Aristolochia species were used as antibacterial, antiinflammatory, antiasthmatic agents, etc. in the Chinese medicine. In previous reserches, aristolochic acids had been proved to be the most potent constituents of Aristolochia species and were reported to be nephrotoxins and carcinogens with long duration for body metabolism. The MeOH extract of the stem was partitioned into CH2Cl2 and H2O layers. The CH2Cl2 layer was subjected to Celite column chromatography into n-Hexane, n-Hexane:EA (1:1), EA, MeOH, n-BuOH and H2O-soluble layers. Among them, which was based on the anti-inflammatory assay, the n-Hexane, n-Hexane:EA (1:1), EA and MeOH-soluble layers showed inhibitory effects on superoxide anion generation and elastase release by human neutrophils which induced by fMLP/CB. In the current phytochemical investigation, the CH2Cl2-soluble layer was subjected to repeated column chromatography. The structures were elucidated by spectroscopic methods that led to the identification of twenty-five compounds, including four aristolochic acids︰ aristolochic acid I (4), aristolochic acid-IIIa (7), aristolochic acid-IVa (6),and aristolochic acid II (5), one sodium salt of aristolochic acids︰sodium aristolochate I (21), five aristolactams ︰aristolatams IIIa (8), aristolactam III (11), aristolactam I (9), aristolactam II (12), and aristolactam Ia (10), three denitroaristolochic acids ︰aristolamide (2), aristolamide II (3), and demethylaristofolin E (16), four aristolochic acid alkyl esters ︰aristolic acid methyl ester (17), 6-methoxyaristolic acid methyl ester (18), aristolochic acid-I methyl ester (13), aristolochic acid-IV methyl ester (14), and aristolochic acid-IVa methyl ester (15), two amides N-trans-feruloylmethoxytyramine (19) and aristopyridinone (25), one benzenoid︰trans-p-Coumaric acid (20), four steroids︰??-sitosteryl-3-O-??-D-glucoside & Stigmasteryl-3-O-??-D-glucoside (22), β-stigmasterol (23), 6β-hydroxystigmast-4-en-3-one (24) and β-sitosterone (25)。 In the anti-inflammatory assay, aristolactam IIIa (8) showed better inhibitory effect on superoxide anion generation and elastase release than genistein, and aristolamide II (3) showed better inhibitory effect on elastase release than genistein.

並列關鍵字

Aristolochia amnshuriensis

參考文獻

第八章參考文獻

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