中草药长叶水麻（Debregeasia Longifolia）和密脉鹅掌柴（Schefflera Venulosa）的抗癌活性成分研究
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摘要
本文采用小鼠乳腺癌细胞tsFT210，以细胞周期抑制、细胞凋亡诱导及细胞坏死为活性指标，对中草药长叶水麻(Debregeasia longifolia)和密脉鹅掌柴(Schefflera venulosa)的醇提浸膏进行了生物活性筛选。结果表明，长叶水麻的醇提浸膏对tsFT210细胞系具有细胞周期抑制作用，密脉鹅掌柴的醇提物具有细胞坏死和细胞周期抑制作用。我们遂采用活性追踪的方法对上述两种中草药的抗癌活性成分进行了初步研究。
长叶水麻生药材的乙醇提取物依次用氯仿、乙酸乙酯、正丁醇萃取，对得到的有效活性部位正丁醇层采用大孔树脂HP-20、MCI柱层析、减压硅胶柱层析、凝胶柱层析(Sephadex LH-20)、反相硅胶柱层析和反相制备高效液相(HPLC)等分离手段分离得到3个单体化合物(1～3)；密脉鹅掌柴生药材用上述同样方法得到活性部位氯仿层，再采用减压硅胶柱层析、凝胶柱层析(Sephadex LH-20)、反相硅胶柱层析和反相制备高效液相(HPLC)等手段分离得到13个单体化合物(4～16)。利用理化性质和光谱学方法(UV、IR、MS、1D-NMR和2D-NMR)阐明了其中14个化合物的结构，分别为3，5-二甲氧基苯甲酸-4-O-β-D-吡喃葡萄糖苷(1)，(-)-表儿茶素(2)，没食子酸(3)，正十六烷酸(4)，正十八烷酸(5)，正二十六烷酸(6)，大黄酚(7)，2，6-二甲氧基对苯醌(8)，2-羟基-3苯胺酰基-1-偶氮苯基-萘(9)β-谷甾醇(10)，4，22-二烯-3-酮豆甾烷(11)，5，22-二烯-7-酮-3β-羟基豆甾烷(12)，齐墩果酮酸(13)，12-α，13-二羟基-齐墩果酮酸(14)。化合物15、16的结构正在鉴定中。
生物活性测试结果表明，化合物4对tsFT210小鼠乳腺癌细胞具有显著的G_2／M期抑制作用，化合物7、13具有较弱的G_2／M期抑制作用，化合物8具有显著的细胞坏死作用，是密脉鹅掌柴的主要抗癌活性成分。
上述化合物1、2、3系首次从长叶水麻中分离得到；化合物4-9，11-14系
中草药长叶水麻和密脉鹅掌柴的抗癌活性成分h）frt 摘要
首次从赛脉鹅掌柴中分离得到，化合物7、8、9、11、12、14系首次从该属中分
离得到，其中14为新化合物；并首次发现化合物7、13具有细胞周川抑制活性。
8具有细胞坏死活性。
本项研究工作为进一步开发应用中草药长叶水麻和密脉鹅掌柴奠定了一定
的化学和生物学当即LIS。
We have undertaken the screening for novel cell cycle inhibitors and apoptosis inducers from the traditional Chinese herbal medicines by use of a mouse cdc2 mutant cell line, tsFT210. In anticipation of achieving the above objectives, traditional Chinese herbal medicines, Debregeasia longifolia and Schefflera venulosa have been screened by using this model and their ethanol-water extract showed bioactivity of inhibiting the cell cycle progression and cytoclasis of tsF210 cells. Thus, we selected them for further investigation.
The ethanol-water extract of Debregeasia longifolia was successively partitioned with CHCls, EtoAc and n-butanol to yield crude extracts. From the bioactive part, n-butanol extract, three compounds 1-3 were isolated by column chromatography on HP-20, MCI, Sephadex LH-20, silica gel and RP18, followed by reverse-phase high performance liquid chromatragraphy and recrystalization. The structures of three compounds 1-3 were elucidated mainly by use of spectroscopic method (UV, IR, MS, 1D-NMR, 2D-NMR) and according to their physicochemical properties: 3,5-diemethoxy benzene carbonic acid-4-O- β -D-Pyranglucose (1), (-)-epicatechin (2), gallic acid (3).
The ethanol-water extract of Schefflera venulosa was successively partitioned with CHCh, EtoAc and n-butanol to yield crude extracts. From the bioactive part, CHCls extract, three compounds 4-16 were isolated by repeated column chromatography on silica gel, Sephadex LH-20 and RP18, followed by recrystalization. The structures of 13 compounds 4-16 were elucidated mainly by use of spectroscopic method (UV, IR, MS, 1D-NMR, 2D-NMR) and according to their physicochemical properties: n-hexadecanoic acid (4), n-stearic acid (5), n-hexacosnic
acid (6), Chrysophanol (7), 2,6-dimethoxyl P -benzoquinone (8), 2-hydroxy-3-( phenylaninocarbonyl ) naphthalene-1-azobenzene (9), β -sitosterol (10), Stigmasta-4, 22-dien-3-one (11), 3 β -hydroxystigmasta-5,22-dien-7-one (12), 3-Oxo-olean-12-ene-28-oic acid, (Oleanonic acid 13), 12 α ,13-dihydroxyolean -3-oxo-olean-28-oic acid (14 ). The structure of compounds 15% 16 are still in deducing.
Bioassay results indicated that compound 4 showed a strong bioactivity in inhibiting the cell progression at the G2/M phase of tsFT210 cells; compound 7 and 13 showed a tender bioactivity in the cell progression at the G2/M phase of tsFT210 cells; compound 8 possessed strong cytoclasis. They are the main anticancer active compounds of this herb.
In summary, compounds 1, 2, 3 were isolated for the first time from Debregeasia longifolia the title plant. Compounds 4-9,11-14 were isolated for the first time from Schefflera venulosa the title plant; 7-9, 11,12,14 were isolated for the first time from the Schefflera genus; and 14 is a new compound. The inhibitory activity on cell cycle of compounds 7, 13 and the cytoclasis activity of compound 8 were also discovered for the first time.
长叶水麻生药材的乙醇提取物依次用氯仿、乙酸乙酯、正丁醇萃取，对得到的有效活性部位正丁醇层采用大孔树脂HP-20、MCI柱层析、减压硅胶柱层析、凝胶柱层析(Sephadex LH-20)、反相硅胶柱层析和反相制备高效液相(HPLC)等分离手段分离得到3个单体化合物(1～3)；密脉鹅掌柴生药材用上述同样方法得到活性部位氯仿层，再采用减压硅胶柱层析、凝胶柱层析(Sephadex LH-20)、反相硅胶柱层析和反相制备高效液相(HPLC)等手段分离得到13个单体化合物(4～16)。利用理化性质和光谱学方法(UV、IR、MS、1D-NMR和2D-NMR)阐明了其中14个化合物的结构，分别为3，5-二甲氧基苯甲酸-4-O-β-D-吡喃葡萄糖苷(1)，(-)-表儿茶素(2)，没食子酸(3)，正十六烷酸(4)，正十八烷酸(5)，正二十六烷酸(6)，大黄酚(7)，2，6-二甲氧基对苯醌(8)，2-羟基-3苯胺酰基-1-偶氮苯基-萘(9)β-谷甾醇(10)，4，22-二烯-3-酮豆甾烷(11)，5，22-二烯-7-酮-3β-羟基豆甾烷(12)，齐墩果酮酸(13)，12-α，13-二羟基-齐墩果酮酸(14)。化合物15、16的结构正在鉴定中。
生物活性测试结果表明，化合物4对tsFT210小鼠乳腺癌细胞具有显著的G_2／M期抑制作用，化合物7、13具有较弱的G_2／M期抑制作用，化合物8具有显著的细胞坏死作用，是密脉鹅掌柴的主要抗癌活性成分。
上述化合物1、2、3系首次从长叶水麻中分离得到；化合物4-9，11-14系
中草药长叶水麻和密脉鹅掌柴的抗癌活性成分h）frt 摘要
首次从赛脉鹅掌柴中分离得到，化合物7、8、9、11、12、14系首次从该属中分
离得到，其中14为新化合物；并首次发现化合物7、13具有细胞周川抑制活性。
8具有细胞坏死活性。
本项研究工作为进一步开发应用中草药长叶水麻和密脉鹅掌柴奠定了一定
的化学和生物学当即LIS。
We have undertaken the screening for novel cell cycle inhibitors and apoptosis inducers from the traditional Chinese herbal medicines by use of a mouse cdc2 mutant cell line, tsFT210. In anticipation of achieving the above objectives, traditional Chinese herbal medicines, Debregeasia longifolia and Schefflera venulosa have been screened by using this model and their ethanol-water extract showed bioactivity of inhibiting the cell cycle progression and cytoclasis of tsF210 cells. Thus, we selected them for further investigation.
The ethanol-water extract of Debregeasia longifolia was successively partitioned with CHCls, EtoAc and n-butanol to yield crude extracts. From the bioactive part, n-butanol extract, three compounds 1-3 were isolated by column chromatography on HP-20, MCI, Sephadex LH-20, silica gel and RP18, followed by reverse-phase high performance liquid chromatragraphy and recrystalization. The structures of three compounds 1-3 were elucidated mainly by use of spectroscopic method (UV, IR, MS, 1D-NMR, 2D-NMR) and according to their physicochemical properties: 3,5-diemethoxy benzene carbonic acid-4-O- β -D-Pyranglucose (1), (-)-epicatechin (2), gallic acid (3).
The ethanol-water extract of Schefflera venulosa was successively partitioned with CHCh, EtoAc and n-butanol to yield crude extracts. From the bioactive part, CHCls extract, three compounds 4-16 were isolated by repeated column chromatography on silica gel, Sephadex LH-20 and RP18, followed by recrystalization. The structures of 13 compounds 4-16 were elucidated mainly by use of spectroscopic method (UV, IR, MS, 1D-NMR, 2D-NMR) and according to their physicochemical properties: n-hexadecanoic acid (4), n-stearic acid (5), n-hexacosnic
acid (6), Chrysophanol (7), 2,6-dimethoxyl P -benzoquinone (8), 2-hydroxy-3-( phenylaninocarbonyl ) naphthalene-1-azobenzene (9), β -sitosterol (10), Stigmasta-4, 22-dien-3-one (11), 3 β -hydroxystigmasta-5,22-dien-7-one (12), 3-Oxo-olean-12-ene-28-oic acid, (Oleanonic acid 13), 12 α ,13-dihydroxyolean -3-oxo-olean-28-oic acid (14 ). The structure of compounds 15% 16 are still in deducing.
Bioassay results indicated that compound 4 showed a strong bioactivity in inhibiting the cell progression at the G2/M phase of tsFT210 cells; compound 7 and 13 showed a tender bioactivity in the cell progression at the G2/M phase of tsFT210 cells; compound 8 possessed strong cytoclasis. They are the main anticancer active compounds of this herb.
In summary, compounds 1, 2, 3 were isolated for the first time from Debregeasia longifolia the title plant. Compounds 4-9,11-14 were isolated for the first time from Schefflera venulosa the title plant; 7-9, 11,12,14 were isolated for the first time from the Schefflera genus; and 14 is a new compound. The inhibitory activity on cell cycle of compounds 7, 13 and the cytoclasis activity of compound 8 were also discovered for the first time.
引文
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5 Purobit M C, et al. Spermicidal activity and chemical analysis of Schefflera venulosa. Fitoterapia, 1993,64(3):274
6 羊晓东，杨丽娟等．植物来源抗肿瘤药物的研究进展．云南农业大学学报，2002，17(3)：276-280
7 张卫东，陈万生．灯盏花中两个新苷类化合物的结构鉴定．中国中药杂志，2001，26(10)：689-690
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16 汪有初，周俊等．管弯花的化学成分．中草药，1999，30(9)：644-645
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2 陈蕾，朱霁虹等．鹅掌柴属化学成分及生理活性研究概况．中药材，25(5)：363-367
3 江庆平，肖倬殷等．惠序鹅掌柴化学成分的研究．华西药学杂志，1990，5(2)：69-71
4 Purohit M C,et al. A new triterpenic acid from Schefflera venulosa. J Nat Prod, 1992,55(3):298
5 Purobit M C, et al. Spermicidal activity and chemical analysis of Schefflera venulosa. Fitoterapia, 1993,64(3):274
6 羊晓东，杨丽娟等．植物来源抗肿瘤药物的研究进展．云南农业大学学报，2002，17(3)：276-280
7 张卫东，陈万生．灯盏花中两个新苷类化合物的结构鉴定．中国中药杂志，2001，26(10)：689-690
8 姚新生主编．有机化合物波谱解析．中国医药科技出版社，2001，18
9 陈昌祥，叶海亚等．红木荷树皮的化学成分．云南植物研究，1997，19(2)：201-206
10 孟令芝，何永炳主编．有机波谱分析．武汉大学出版社，1997，32
11 王雪松，车庆明等．山楂核化学成份研究．中国中药杂志，1999，24(12)：739-740
12 王文祥，顾明等．川芎化学成份研究．中草药，2002，33(1)：4-5
13 李志诚，左春旭．荷叶化学成分的研究．中草药，1996，27(A09)：50-52
14 陶朝阳，陈万生．刺异叶花椒化学成分研究．药学学报，2001，36(7)：511-513
15 吕泰省，易杨华．铁刀目的蒽醌类成份研究．药学学报，2001，36(7)：547-548
16 汪有初，周俊等．管弯花的化学成分．中草药，1999，30(9)：644-645
17 唐恢同主编．有机化合物的光谱鉴定．北京大学出版社，1994：142
18 姚新生主编．天然药物化学(第二版)．人民卫生出版社，1988：(a) 412，(b)347
19 王岩，周莉玲．显齿蛇葡萄化学成分的研究．中药材，2002，
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