麻叶千里光抗菌活性成分的研究
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摘要
麻叶千里光(Senecio cannabifolius Less.)又名宽叶返魂草，为菊科(Compositae)千里光属(Senecio L.)多年生草本植物，主要分布于我国东北、河北等地及朝鲜、日本、前苏联远东地区，生长于山沟林缘及湿草甸上。本品味苦、性凉，具有散瘀、止血、止痛的功效，在民间被广泛用于病毒性感冒、各类炎症的治疗。以该植物为原料的中药制剂现有肺宁颗粒、返魂草注射剂等。该属植物的化学成分特征是含有吡咯里西啶类生物碱(pyrrolizidine alkaloids)，此类生物碱对人、家畜的肝脏具有很大的毒性，并且存在潜在的致癌危险。2004年美国、欧洲各药品监督管理部门对中国出口的同属植物千里光(S. scandens Buch.-Ham.ex D.Don)的各种制剂进行了封杀。为了解决本品显著疗效与较大毒性之间的矛盾，配合长春华康制药有限公司对该品种的二次开发，我们对麻叶千里光抗菌有效成分进行了较为详细的研究。
药效学实验结果表明，麻叶千里光水提取物具有较明显的抗菌、抗病毒作用，显著的解热、镇痛、抗炎、祛痰、止咳、平喘及增强免疫的作用，并有一定的抗过敏作用。其药效作用与临床作用一致。
本论文以革兰氏阳性菌金黄色葡萄球菌(Staphylococcus aureus)、枯草芽孢杆菌(Bacillus subtilis)和阴性菌大肠杆菌(Escherichia coli)为受试菌，采用体外抑菌圈法追踪抗菌活性部分，利用各种色谱技术，从麻叶千里光全草的水提醇沉物中，分离得到了52个化合物。根据理化性质和谱学数据鉴定了其中30个化合物的结构。其中新化合物有10个，分别为麻叶千里光碱A(Cannabiloid A, E-10)、麻叶千里光碱B(Cannabiloid B, B-6)、麻叶千里光碱C(Cannabiloid C, B-9)、麻叶千里光碱D(Cannabiloid D, B-10)、麻叶千里光苷A(Cannabiside A, E-15)、麻叶千里光苷B(Cannabiside B, B-2)、麻叶千里光苷C(Cannabiside C, B-5)、麻叶千里光苷D(Cannabiside D, B-13)、麻叶千里光苷E(Cannabiside E, B-20)、麻叶千里光内酯A(Cannabilactone A, C-4)；一个新天然产物：4-(吡咯烷-2-酮基)-苯基乙酸(4-(pyrrolidin-2-one)-phenyl acetic acid, C-1)。首次从千里光属植物(Senecio L.)中分离得到了14个化合物，它们分别是：对-羟基苯乙酸甲酯(methyl ρ-hydroxy ben-zeneacetate, E-3)、3，4-二羟基苯甲酸(3，4-dihydroxy benzoic acid, E-4)、2，5-
沈阳药科大学博士学位论文
中文摘要
二经基苯乙酸(2，5一ihyd『OXyl benzeneaCetic aeid，E一5)、2，5一二轻基苯乙酸甲酷
(mathyl一2，5劝hydroxy benzeneacetate，E一8)、3一轻基礴一甲氧基苯甲酸(3一hydroXy礴-
mathoXy benzoie aeid，E一11)、5一轻基毗陡一2一甲酸甲醋(methyl一5一hydrOXy.2一Pyridine-
ca由oXylate，E一13)、(6R，7as)6一HydroXy一7，7a一dihydro一2(6H)一benzofuranone(E一14)、
2一(1，4一二轻基环己烷基)一乙酸(2一(1，4一dihydroxycyclohexanyl)一acetie aeid，E一16)、
3一轻基环己酸(3一hydroxyeyelohexanecarboXylie aeid，E一17)、4一轻基苯甲醛(4一hydroxy
benzaldehyde，B一14)、节基一O一奋L一口比喃阿拉伯糖基(1一6)井D一毗喃葡萄糖昔(benZyl
6一O一全L一arabinoPyranosyl一声D一glucoPyranoside，B一16)、(6S，95)6一轻基一3一酮一a-紫罗
兰醇一g一。声。一葡萄糖昔((65，95)9.0.声D习Iucopyranosy.oxy-6一hydroX梦3一OxO一企
ionol，B一18)、(65，gR)6一轻基一3一酮一a-紫罗兰醇一9一O咨D一葡萄糖普((65，gR)9.0咨D一lu-
eoPyranosyloXy一hydroxy-3一oxo一份ionol，B一19)、消旋丁香脂素((士)liriodendrin，C一2)。
还有3个其他已知化合物:对一经基苯乙酸(P-hydroxy benzeneaCetic acid，E一1)、对-
二苯酚(1，4一benzenediol，E一2)、邻轻基苯甲酸(o一hyd『OXy benzoic acid，E一9)、对
经基苯甲酸(P-hydroXy benzoie aeid，E一12)、p一谷街醇(p一s如St6rol，C毛)。
体外抑菌实验表明，除水层外，各萃取部分均显抑菌活性，其中乙酸乙醋部分活性
最强，能够显著抑制革兰氏阳性菌(金黄色葡萄球菌、枯草芽抱杆菌)，对革兰氏阴性
大肠杆菌作用较弱。有效成分的分离鉴定结果显示，酚酸类物质是本品主要抗菌活性物
质，利用比浊法测定化合物E一1~E一12的最小抑菌浓度(Mlc)，并对其构效关系进行
了初步的讨论。
一般药理学研究显示，在高、中、低剂量下麻叶千里光提取物对试验动物中枢神经
系统、心血管系统、呼吸系统无明显影响;急性毒性、长期毒性试验表明麻叶千里光提
取物基本无毒。
本文采用均匀设计安排实验，通过高效液相色谱法和分光光度法测定麻叶千里光提
取物中绿原酸、咖啡酸、寡糖的含量，以此作为指标，考察了粉碎程度、加水量、提取
时间、提取次数、醇沉密度、醇沉浓度等6个因素对三者提取率的影响，实验结果用
UROS软件系统和人工神经智能网络技术(art币eia!neura!ne七~O水，ANN)进行处理，
优选出三者合理的提取工艺，为生产工艺参数的选择提供了实验依据。为了对该产品的
生产进行质量监控，建立一个产品质量检验的方法，我们采用非水电位滴定法对本品的
水提醇沉物?
Doctor Candidate: Bin Wu Supervisor: Prof. Lijun Wu
Prof. Chulsa Kim
Senecio cannabifolius Less., whose another name is "Kuan Ye Fan Hun Cao", as one species of Senecio genus of Compositae family, distributes mainly in the North east and Hebei Province of China, Korea, Japan and far east of pre-Soviet Union.
The taste of this plant is bitter, and natured character is cool. While its function shows the effects on dispelling ecchymoma, anastalsis and analgesic. As one kind of folk medicine, it's usually used to treat the diseases, such as virus influenza and many kinds of inflammatories.
The character on its chemical constituents lies in the pyrrolizidine alkaloids, which exhibited the chronical hepatotoxicity (liver toxicity) and cancerigenic possibility to the human beings and domestic animals.
In 2004, the importing of many kinds of preparations made from the species of Senecio genus from China had been prohibited by American and Europe drug administrative departments.
In order to deal with the contradiction between the toxicity and efficiency on the treatment, to find the antibacterial compounds and made cooperation on the exploitation of this plant with Chang Chun Hua kang Pharm. Co. Ltd., the further research on the chemical constituents and their anti-virus activity were studied.
Pharmacodynamics tests showed that the aqueous extract of Senecio cannabifolius Less, had the effect on antibiosis, antivirus, analgesic- antipyretic, anti-inflammatory antihechic, antianaphylaxis and immunoregulatory, etc., and also showed the same effect when it was used for clinical treatment.
By many kinds of isolation method, such as silica gel chromatographies, Lobar column, semi-PHPLC and so on, 52 compounds were obtained and the structures of thirty of them were identified by their physico-chemical character and spectra, and comparison the data with the reference for them.
Among the 30 compounds, ten of them were novel compounds. They were identified as Cannabiloid A (E-10), Cannabiloid B (B-6), Cannabiloid C (B-9), Cannabiloid D (B-10), Cannabiside A (E-15), Cannabiside B (B-2), Cannabiside C (B-5), Cannabiside D (B-13), Cannabiside E (B-20), Cannabilactone A(C-4). One new natural compound: 4-(pyrrolidin-2-one)-phenyl acetic acid (C-1). At same time, fourteen of them were isolated from the Senecio genus for the first time. They were elucidated as methyl p-hydroxy benzeneacetate (E-3), 3,4-dihydroxy benzoic acid (E-4), 2,5-dihydroxyl benzeneacetic acid (E-5), methyl 2,5-dihydroxy benzeneacetate (E-8), 3-hydroxy-4-methoxy benzoic acid (E-11), methyl-5-hydroxy-2-pyridinecarboxy-late (E-13), (6R,7aS)6-Hydroxy-7,7a-dihydro-2(6H)-benzofuranone (E-14), 2-(1,4-di-hydroxycyclohexanyl)-acetic acid (E-16), 3-hydroxycyclohexanecarboxylic acid (E-17), 4-hydroxy benzaldehyde (B-14), benzyl 6-O-a-L-arabinopyranosyl-B-D-glucopyrano-side (B-16), (6S,9S)9-O-B-D-glucopyranosyloxy-6-hydroxy-3-oxo-a-ionol (B-18), (6S, 9R)9-O-B-D-glucopyranosyloxy-6-hydroxy-3-oxo-a-ionol (B-19), (+)liriodendrin (C-2).
By the anti-bacteria (screening) assay in vitro, the CHCI3, EtOAc and n-BuOH soluble fractions, except for the water layer also showed the potent anti-bacteria activities. Among them, the EtOAc layer exhibited the best result, which gave the potent activity against gram-positive bacilli, such as Staphylococcus aureus, Bacillus subtilis. By the chemical isolation, the main compounds of this part were phenolic constituents, and structure-activity relationship of compounds E-1~E-12 were discussed simply.
The general pharmacological studies indicated that the high, medium and low dose of the extract had no influence on the central nervous system, cardiovascular and respiratory system. At same time, the tests of the extract on acute toxicity and secular toxicity showed no toxicity.
Contents, such as chlorogenic acid, caffeic acid and oligosaccharides from the extrat of Senecio cannabofolius Less, were examined by HPLC and spectrophoto-metry with uniform design, and six factors, such as the extent of crush, amount of water,
药效学实验结果表明，麻叶千里光水提取物具有较明显的抗菌、抗病毒作用，显著的解热、镇痛、抗炎、祛痰、止咳、平喘及增强免疫的作用，并有一定的抗过敏作用。其药效作用与临床作用一致。
本论文以革兰氏阳性菌金黄色葡萄球菌(Staphylococcus aureus)、枯草芽孢杆菌(Bacillus subtilis)和阴性菌大肠杆菌(Escherichia coli)为受试菌，采用体外抑菌圈法追踪抗菌活性部分，利用各种色谱技术，从麻叶千里光全草的水提醇沉物中，分离得到了52个化合物。根据理化性质和谱学数据鉴定了其中30个化合物的结构。其中新化合物有10个，分别为麻叶千里光碱A(Cannabiloid A, E-10)、麻叶千里光碱B(Cannabiloid B, B-6)、麻叶千里光碱C(Cannabiloid C, B-9)、麻叶千里光碱D(Cannabiloid D, B-10)、麻叶千里光苷A(Cannabiside A, E-15)、麻叶千里光苷B(Cannabiside B, B-2)、麻叶千里光苷C(Cannabiside C, B-5)、麻叶千里光苷D(Cannabiside D, B-13)、麻叶千里光苷E(Cannabiside E, B-20)、麻叶千里光内酯A(Cannabilactone A, C-4)；一个新天然产物：4-(吡咯烷-2-酮基)-苯基乙酸(4-(pyrrolidin-2-one)-phenyl acetic acid, C-1)。首次从千里光属植物(Senecio L.)中分离得到了14个化合物，它们分别是：对-羟基苯乙酸甲酯(methyl ρ-hydroxy ben-zeneacetate, E-3)、3，4-二羟基苯甲酸(3，4-dihydroxy benzoic acid, E-4)、2，5-
沈阳药科大学博士学位论文
中文摘要
二经基苯乙酸(2，5一ihyd『OXyl benzeneaCetic aeid，E一5)、2，5一二轻基苯乙酸甲酷
(mathyl一2，5劝hydroxy benzeneacetate，E一8)、3一轻基礴一甲氧基苯甲酸(3一hydroXy礴-
mathoXy benzoie aeid，E一11)、5一轻基毗陡一2一甲酸甲醋(methyl一5一hydrOXy.2一Pyridine-
ca由oXylate，E一13)、(6R，7as)6一HydroXy一7，7a一dihydro一2(6H)一benzofuranone(E一14)、
2一(1，4一二轻基环己烷基)一乙酸(2一(1，4一dihydroxycyclohexanyl)一acetie aeid，E一16)、
3一轻基环己酸(3一hydroxyeyelohexanecarboXylie aeid，E一17)、4一轻基苯甲醛(4一hydroxy
benzaldehyde，B一14)、节基一O一奋L一口比喃阿拉伯糖基(1一6)井D一毗喃葡萄糖昔(benZyl
6一O一全L一arabinoPyranosyl一声D一glucoPyranoside，B一16)、(6S，95)6一轻基一3一酮一a-紫罗
兰醇一g一。声。一葡萄糖昔((65，95)9.0.声D习Iucopyranosy.oxy-6一hydroX梦3一OxO一企
ionol，B一18)、(65，gR)6一轻基一3一酮一a-紫罗兰醇一9一O咨D一葡萄糖普((65，gR)9.0咨D一lu-
eoPyranosyloXy一hydroxy-3一oxo一份ionol，B一19)、消旋丁香脂素((士)liriodendrin，C一2)。
还有3个其他已知化合物:对一经基苯乙酸(P-hydroxy benzeneaCetic acid，E一1)、对-
二苯酚(1，4一benzenediol，E一2)、邻轻基苯甲酸(o一hyd『OXy benzoic acid，E一9)、对
经基苯甲酸(P-hydroXy benzoie aeid，E一12)、p一谷街醇(p一s如St6rol，C毛)。
体外抑菌实验表明，除水层外，各萃取部分均显抑菌活性，其中乙酸乙醋部分活性
最强，能够显著抑制革兰氏阳性菌(金黄色葡萄球菌、枯草芽抱杆菌)，对革兰氏阴性
大肠杆菌作用较弱。有效成分的分离鉴定结果显示，酚酸类物质是本品主要抗菌活性物
质，利用比浊法测定化合物E一1~E一12的最小抑菌浓度(Mlc)，并对其构效关系进行
了初步的讨论。
一般药理学研究显示，在高、中、低剂量下麻叶千里光提取物对试验动物中枢神经
系统、心血管系统、呼吸系统无明显影响;急性毒性、长期毒性试验表明麻叶千里光提
取物基本无毒。
本文采用均匀设计安排实验，通过高效液相色谱法和分光光度法测定麻叶千里光提
取物中绿原酸、咖啡酸、寡糖的含量，以此作为指标，考察了粉碎程度、加水量、提取
时间、提取次数、醇沉密度、醇沉浓度等6个因素对三者提取率的影响，实验结果用
UROS软件系统和人工神经智能网络技术(art币eia!neura!ne七~O水，ANN)进行处理，
优选出三者合理的提取工艺，为生产工艺参数的选择提供了实验依据。为了对该产品的
生产进行质量监控，建立一个产品质量检验的方法，我们采用非水电位滴定法对本品的
水提醇沉物?
Doctor Candidate: Bin Wu Supervisor: Prof. Lijun Wu
Prof. Chulsa Kim
Senecio cannabifolius Less., whose another name is "Kuan Ye Fan Hun Cao", as one species of Senecio genus of Compositae family, distributes mainly in the North east and Hebei Province of China, Korea, Japan and far east of pre-Soviet Union.
The taste of this plant is bitter, and natured character is cool. While its function shows the effects on dispelling ecchymoma, anastalsis and analgesic. As one kind of folk medicine, it's usually used to treat the diseases, such as virus influenza and many kinds of inflammatories.
The character on its chemical constituents lies in the pyrrolizidine alkaloids, which exhibited the chronical hepatotoxicity (liver toxicity) and cancerigenic possibility to the human beings and domestic animals.
In 2004, the importing of many kinds of preparations made from the species of Senecio genus from China had been prohibited by American and Europe drug administrative departments.
In order to deal with the contradiction between the toxicity and efficiency on the treatment, to find the antibacterial compounds and made cooperation on the exploitation of this plant with Chang Chun Hua kang Pharm. Co. Ltd., the further research on the chemical constituents and their anti-virus activity were studied.
Pharmacodynamics tests showed that the aqueous extract of Senecio cannabifolius Less, had the effect on antibiosis, antivirus, analgesic- antipyretic, anti-inflammatory antihechic, antianaphylaxis and immunoregulatory, etc., and also showed the same effect when it was used for clinical treatment.
By many kinds of isolation method, such as silica gel chromatographies, Lobar column, semi-PHPLC and so on, 52 compounds were obtained and the structures of thirty of them were identified by their physico-chemical character and spectra, and comparison the data with the reference for them.
Among the 30 compounds, ten of them were novel compounds. They were identified as Cannabiloid A (E-10), Cannabiloid B (B-6), Cannabiloid C (B-9), Cannabiloid D (B-10), Cannabiside A (E-15), Cannabiside B (B-2), Cannabiside C (B-5), Cannabiside D (B-13), Cannabiside E (B-20), Cannabilactone A(C-4). One new natural compound: 4-(pyrrolidin-2-one)-phenyl acetic acid (C-1). At same time, fourteen of them were isolated from the Senecio genus for the first time. They were elucidated as methyl p-hydroxy benzeneacetate (E-3), 3,4-dihydroxy benzoic acid (E-4), 2,5-dihydroxyl benzeneacetic acid (E-5), methyl 2,5-dihydroxy benzeneacetate (E-8), 3-hydroxy-4-methoxy benzoic acid (E-11), methyl-5-hydroxy-2-pyridinecarboxy-late (E-13), (6R,7aS)6-Hydroxy-7,7a-dihydro-2(6H)-benzofuranone (E-14), 2-(1,4-di-hydroxycyclohexanyl)-acetic acid (E-16), 3-hydroxycyclohexanecarboxylic acid (E-17), 4-hydroxy benzaldehyde (B-14), benzyl 6-O-a-L-arabinopyranosyl-B-D-glucopyrano-side (B-16), (6S,9S)9-O-B-D-glucopyranosyloxy-6-hydroxy-3-oxo-a-ionol (B-18), (6S, 9R)9-O-B-D-glucopyranosyloxy-6-hydroxy-3-oxo-a-ionol (B-19), (+)liriodendrin (C-2).
By the anti-bacteria (screening) assay in vitro, the CHCI3, EtOAc and n-BuOH soluble fractions, except for the water layer also showed the potent anti-bacteria activities. Among them, the EtOAc layer exhibited the best result, which gave the potent activity against gram-positive bacilli, such as Staphylococcus aureus, Bacillus subtilis. By the chemical isolation, the main compounds of this part were phenolic constituents, and structure-activity relationship of compounds E-1~E-12 were discussed simply.
The general pharmacological studies indicated that the high, medium and low dose of the extract had no influence on the central nervous system, cardiovascular and respiratory system. At same time, the tests of the extract on acute toxicity and secular toxicity showed no toxicity.
Contents, such as chlorogenic acid, caffeic acid and oligosaccharides from the extrat of Senecio cannabofolius Less, were examined by HPLC and spectrophoto-metry with uniform design, and six factors, such as the extent of crush, amount of water,
引文
[1] 中国植物志，第77卷，第1分册．中国科学院中国植物志编辑委员会．北京：科学出版社,1999年4月．
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[14] Serena Catalano, Stefano Luschi, Guido Flamini, et al. A xanthone from Senecio mikanioides leaves. Phytochemistry, 1996, 42(6): 1605-1607.
[15] Mario D'Agostino, Vincenzo De Feo, Francesco De Simone, et al. Three chalcones from Senecio pseudotites. Phytochemistry, 1991, 30(7): 2440-2441.
[16] Kenjiro Toki, Norio Saito, Harumitsu Kuwano, et al. Acylated pelargonidin 3,7-glycosides from pink flowers of Senecio cruentus. Phytochemistry, 1995, 38(6): 1509-1512.
[17] I. Piegay, J. Reynaud, J. Raynaud. Les flavonoides de Senecio aureus L. (Compos(?)es). Pharmazie, 1996, 41: 524-525.
[18] 程卫强，隋长惠，袁久志．羽叶千里光黄酮类成分的研究．中草药，1999．30(10)：727-729．
[19] S. Pena Betancourt, A. Proliac, J. Rayhaud. Quatre mono-O-glycosyl flavonoids des tiges feuillees de Senecio sanguisorbae DC. (Compos(?)es). Pharmazie, 1988, 43: 142-143.
[20] Toshio Goto, Tadao Kondo, Takatoshi Kawai, et al. Structure of cinerarin, a tetra-acylated anthocyanin isolated from the blue garden cineraria, Senecio cruentus. Tetrahedron Letters, 1984, 25(2): 6021-6024.
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[24] Ferdinnand Bohlmann, Christa Zdero, Robert M. King, et al. The first acetylenic monoterpene and other constituents from Senecio clevelandii. Phytochemistry, 1981, 20(10): 2425-2427.
[25] Elizabeth A. Jares, Maria Cristina Tettamanzi, Alicia B. Pomilio. PSitosterol 3-O-β-D-glucuronopyranoside from Senecio bonanensis, hytochemistry, 1990, 29(1): 340-341.
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[28] N.S. Hussein. Benzofurans from Senecio desfontainei. Pharmazie, 1992, 47: 468-469.
[29] 陈芬，钟越，李妍。等．麻叶千里光对免疫功能影响的实验研究．浙江中西医结合杂志．2002，12(6)：354-355．
[30] 刘方．武子斌．牛淑敏，等．中药材抗氧化及自由基清除活性的研究．中国药学杂志，2001，36(7)：442-445．
[31] 尹洪萍，袁红，华春珍，等．10种中药对耐药性肺炎链球菌的抑菌作用．医药导报。2003，22(7)：483-484．
[32] 袁昌衡，周启贵．杨飞，等．80种中药水煎液对淋球菌的抑制试验．中国医院药学杂志，1997，17(11)：508-509．
[33] 陈进军，王建华，周景明．改良千里光注射液的体内外抗菌作用及安全性．中国兽医学报，2001，21(6)：608-609．
[34] 陈进军，周景明．千里光的化学成分鉴定及体外抗菌试验．动物医学进展．1999，20(4)：35-37．
[35] 王雪芬，屠殿君．九里明化学成分的研究．药学学报．1980．15(8)：503-504．
[36] 周欣，赵超，杨小生．气相色谱．质谱分析黔产千里光挥发油的化学成分．中草药．2001，32(10)：880-881．
[37] 司红丽。王建娜，王跃虎。等．狗舌草黄酮类化合物对3种肿瘤细胞的药物敏感试验．药物生物技术，2003，10(4)：229-231．
[38] 吴树荣，蔡定国，卢涌泉，等．峨眉千里光A碱的提取和抗肿瘤作用．中草药，1983，14(5)：45．
[39] 曾美怡．李敏民．赵秀文．含吡咯双烷生物碱中草药的毒性(一)——吡咯双烷生物碱的毒性反应中药．新药与临床药理．1996，7(3)：44-47．
[40] 赵显国，王峥涛，张勉，等．肝毒吡咯里西啶生物碱与中草药．中草药，1998．29(5)：343-345．
[41] 陈鹭声，宋万志．中国菊科药用植物研究概况．中草药．1987．18(9)：37-45．
[42] 余诚方．双稠吡咯啶生物碱的生物活性及药效研究．中国药学杂志，1989，24(10)：585-587．
[43] 罗金花．千里光、白饭树治疗新生儿脓疱疮的临床观察．医学文选．1999，18(5)：802-803．
[44] 张卫明，赵泊涛，马世宏．等．千里光在皮肤洗剂中的应用．中国野生植物资源．1995．3：48．
[45] 项迎春，王建平．千里光滴眼液的研制及临床应用．中国药业，2001，10(12)：34-35．
[46] 张庆莲，陈艳，施晓哲，等．返魂草滴眼液对单纯疱疹性角膜炎的疗效观察．长春中医学院学报．1999，15(4)：91．
[47] 董亮．杨锡远．草药千里光临床疗效观察．现代医药卫生，2002．18(6)：498．
[48] 张云，王湖．返魂草冲剂治疗慢性气管炎30例疗效观察．佳木斯医学院学报．1994，17(2)：45-46．
[49] 俞荣森，周光军，李茂才．光花栓治疗慢性前列腺炎疗效观察．浙江中西医结合杂志，1999，9(4)：250-251．
[50] Zhi-Ben Tu, Chohachi Konno, D.Doel Soejarto, et al. Indentiflcation of senecionine and senecionine N-oxide as antifertility constituents in Senecio vulgaris. Journal of Pharmaceutical Scienecen, 1988, 77(5):461-463.
[51] 俸士林，韦旭日．土三七外敷治疗急性软组织损伤160例报告．中华临床新医学，2002，2(6)：574．
[52] 汤效群，沈悦．通络止痛法治疗带状疱疹后遗神经痛60例．安徽中医学院学报，1997，16(4)：28．
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[7] 赵显国，王峥涛，徐国钧，等．肝毒吡咯里西啶生物碱与中草药．中草药，1998，29(5)：343．
[8] 袁继丽．中草药致肝损害的研究近况．中草药．1999．30(9)：711．
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[13] 胡金锋，冯孝章．贾忠建．高属和千里光属植物中桉烷型倍半萜的光谱特征．天然产物研究与开发．1999．11(4)：95-102．
[14] Serena Catalano, Stefano Luschi, Guido Flamini, et al. A xanthone from Senecio mikanioides leaves. Phytochemistry, 1996, 42(6): 1605-1607.
[15] Mario D'Agostino, Vincenzo De Feo, Francesco De Simone, et al. Three chalcones from Senecio pseudotites. Phytochemistry, 1991, 30(7): 2440-2441.
[16] Kenjiro Toki, Norio Saito, Harumitsu Kuwano, et al. Acylated pelargonidin 3,7-glycosides from pink flowers of Senecio cruentus. Phytochemistry, 1995, 38(6): 1509-1512.
[17] I. Piegay, J. Reynaud, J. Raynaud. Les flavonoides de Senecio aureus L. (Compos(?)es). Pharmazie, 1996, 41: 524-525.
[18] 程卫强，隋长惠，袁久志．羽叶千里光黄酮类成分的研究．中草药，1999．30(10)：727-729．
[19] S. Pena Betancourt, A. Proliac, J. Rayhaud. Quatre mono-O-glycosyl flavonoids des tiges feuillees de Senecio sanguisorbae DC. (Compos(?)es). Pharmazie, 1988, 43: 142-143.
[20] Toshio Goto, Tadao Kondo, Takatoshi Kawai, et al. Structure of cinerarin, a tetra-acylated anthocyanin isolated from the blue garden cineraria, Senecio cruentus. Tetrahedron Letters, 1984, 25(2): 6021-6024.
[21] Ferdinand Bohlmann, Christa Zdero. Sandaracopimarene derivatives from Senecio subrubriflorus.Phytochemistry, 1982, 21 (7): 1697-1700.
[22] Dong-Liang Cheng, Xiao-Ping Cao, Jie-Kai Cheng, et al. Diterpene glycosides from Senecio rufus. Phytochemistry, 1993, 32(1): 151-153.
[23] N. Di. Tommasl, L. Rastrelli, M. R. Lauro, et al. Polyhydroxylated trierepenes from Senecio pseudotites. Phytochemistry, 1998, 49(4): 1123-1125.
[24] Ferdinnand Bohlmann, Christa Zdero, Robert M. King, et al. The first acetylenic monoterpene and other constituents from Senecio clevelandii. Phytochemistry, 1981, 20(10): 2425-2427.
[25] Elizabeth A. Jares, Maria Cristina Tettamanzi, Alicia B. Pomilio. PSitosterol 3-O-β-D-glucuronopyranoside from Senecio bonanensis, hytochemistry, 1990, 29(1): 340-341.
[26] Elizabeth Jares, Alicia B. Pomilio. Pyrrolizidine alkaloids and other components of Senecio vira-vira. Journal of Natural Products, 1986, 50(3): 514.
[27] Alejando F. Barrero, Juan F. Sanchez, E. J. Alvarez-Manzaneda R., et al. Di-O-acyl derivatives of shikimic acid from Senecio nerbrodensis. Phytochemistry, 1988, 27(4): 1191-1193.
[28] N.S. Hussein. Benzofurans from Senecio desfontainei. Pharmazie, 1992, 47: 468-469.
[29] 陈芬，钟越，李妍。等．麻叶千里光对免疫功能影响的实验研究．浙江中西医结合杂志．2002，12(6)：354-355．
[30] 刘方．武子斌．牛淑敏，等．中药材抗氧化及自由基清除活性的研究．中国药学杂志，2001，36(7)：442-445．
[31] 尹洪萍，袁红，华春珍，等．10种中药对耐药性肺炎链球菌的抑菌作用．医药导报。2003，22(7)：483-484．
[32] 袁昌衡，周启贵．杨飞，等．80种中药水煎液对淋球菌的抑制试验．中国医院药学杂志，1997，17(11)：508-509．
[33] 陈进军，王建华，周景明．改良千里光注射液的体内外抗菌作用及安全性．中国兽医学报，2001，21(6)：608-609．
[34] 陈进军，周景明．千里光的化学成分鉴定及体外抗菌试验．动物医学进展．1999，20(4)：35-37．
[35] 王雪芬，屠殿君．九里明化学成分的研究．药学学报．1980．15(8)：503-504．
[36] 周欣，赵超，杨小生．气相色谱．质谱分析黔产千里光挥发油的化学成分．中草药．2001，32(10)：880-881．
[37] 司红丽。王建娜，王跃虎。等．狗舌草黄酮类化合物对3种肿瘤细胞的药物敏感试验．药物生物技术，2003，10(4)：229-231．
[38] 吴树荣，蔡定国，卢涌泉，等．峨眉千里光A碱的提取和抗肿瘤作用．中草药，1983，14(5)：45．
[39] 曾美怡．李敏民．赵秀文．含吡咯双烷生物碱中草药的毒性(一)——吡咯双烷生物碱的毒性反应中药．新药与临床药理．1996，7(3)：44-47．
[40] 赵显国，王峥涛，张勉，等．肝毒吡咯里西啶生物碱与中草药．中草药，1998．29(5)：343-345．
[41] 陈鹭声，宋万志．中国菊科药用植物研究概况．中草药．1987．18(9)：37-45．
[42] 余诚方．双稠吡咯啶生物碱的生物活性及药效研究．中国药学杂志，1989，24(10)：585-587．
[43] 罗金花．千里光、白饭树治疗新生儿脓疱疮的临床观察．医学文选．1999，18(5)：802-803．
[44] 张卫明，赵泊涛，马世宏．等．千里光在皮肤洗剂中的应用．中国野生植物资源．1995．3：48．
[45] 项迎春，王建平．千里光滴眼液的研制及临床应用．中国药业，2001，10(12)：34-35．
[46] 张庆莲，陈艳，施晓哲，等．返魂草滴眼液对单纯疱疹性角膜炎的疗效观察．长春中医学院学报．1999，15(4)：91．
[47] 董亮．杨锡远．草药千里光临床疗效观察．现代医药卫生，2002．18(6)：498．
[48] 张云，王湖．返魂草冲剂治疗慢性气管炎30例疗效观察．佳木斯医学院学报．1994，17(2)：45-46．
[49] 俞荣森，周光军，李茂才．光花栓治疗慢性前列腺炎疗效观察．浙江中西医结合杂志，1999，9(4)：250-251．
[50] Zhi-Ben Tu, Chohachi Konno, D.Doel Soejarto, et al. Indentiflcation of senecionine and senecionine N-oxide as antifertility constituents in Senecio vulgaris. Journal of Pharmaceutical Scienecen, 1988, 77(5):461-463.
[51] 俸士林，韦旭日．土三七外敷治疗急性软组织损伤160例报告．中华临床新医学，2002，2(6)：574．
[52] 汤效群，沈悦．通络止痛法治疗带状疱疹后遗神经痛60例．安徽中医学院学报，1997，16(4)：28．