藏茵陈活性组分的制备分离和化学表征
|
摘要
藏茵陈是传统高寒藏药，在治疗肝胆疾病方面具有独特疗效。龙胆科植物抱茎獐牙菜是我国青藏高原特有植物，常作为藏茵陈的主要原料入药，临床治疗急慢性肝炎疗效显著。为充分阐释藏茵陈的化学物质基础，本论文对抱茎獐牙菜的活性组分进行了系统的制备分离和化学表征，主要工作如下：
首先建立了药材甲醇粗提物的HPLC-UV-MS联用分析方法，获得了粗提物中各种成分的结构信息，为确定分离制备的目标和策略提供了依据。利用各种硅胶层析方法从药材脂溶性部位中分离制备了14个单体，包括11个(口山)酮甙元，其中7个为首次从抱茎獐牙菜中分离得到。从药材正丁醇萃取部位中分离表征了24个化合物，其中包括2个新(口山)酮甙和2个新环烯醚萜甙，有4个环烯醚萜甙、7个(口山)酮甙、1个黄酮甙及赤矢车菊素为首次从抱茎獐牙菜中分离到。用HPLC-UV-MS技术对分离到的一个环烯醚萜组分进行了在线分析表征，推测了其中两个微量新环烯醚萜甙的结构。
用单扫描示波极谱法和荧光分光光度法测定了Bellidifolin等5种(口山)酮甙元的抗自由基作用，结果均表现出较强的抑制超氧阴离子自由基和羟基自由基作用。通过缺血性脑损伤动物模型的药理研究，首次发现Bellidifolin具有较强的脑保护作用，显示了良好的应用前景。论文还归纳总结了天然氧代(口山)酮及其甙类化合物的~1H和~(13)C核磁共振谱学规律，为(口山)酮类化合物的核磁共振表征提供了理论依据。
'Zang-Yin-Chen' ( ZYC) is a traditional Tibetan medicine for the treatment of hepatitis and cholecystitis. The plant Swertia franchetiana Smith (family Gentianaceae) is distributed in Qinghai-Tibet Plateau and used as plant materials of ZYC. In order to clarify the chemical foundation of this herb, the dissertation describes the preparation, isolation and characterization of bioactive principles from S. franchetiana. The main research results are as follows:
The methanol crude extract of ZYC was screened by means of combined HPLC-UV-MS technique. The structural information was obtained from on-line UV and MS spectra at the early stage of preparative isolation. Phytochemical investigation of liposoluble fractions of the methanol extracts led to the isolation of fourteen pure compounds including eleven xanthone aglycones, of which seven compounds were isolated from this plant for the first time. Additional twenty-four compounds were isolated and characterized from n-BuOH fractions of methanol extracts from ZYC. Among them, two new iridoid glycosides and two new xanthone glycosides were obtained by means of preparative HPLC. The other 4 iridoid glycosides and 7 xanthone glycosides, together with isovitexin and erythrocentaurin, were all firstly found from this plant. Besides, two minor compounds from an aqueous fraction were tentatively identified as two new iridoid glycosides by means of HPLC-UV-MS analysis.
Five xanthones from this plant were tested for the properties of radical scavenging by means of oscillopolarography and fluorescent spectrophotometry, and showed
capacity to scavenge both superoxide anion radical and hydroxyl radical. Bellidifolin was further tested for the protective activity on cerebral-ischemia animals in vivo. The results revealed that Bellidifolin possessed potent brain-protective activity and showed prospects of pharmaceutical application.
The 1H and 13C NMR data of natural xanthones from ZYC and literatures were analyzed and summarized. Some rules of 1H and 13C chemical shifts were deduced in order to supply a theoretic reference for the NMR characterization of natural xanthone compounds.
首先建立了药材甲醇粗提物的HPLC-UV-MS联用分析方法，获得了粗提物中各种成分的结构信息，为确定分离制备的目标和策略提供了依据。利用各种硅胶层析方法从药材脂溶性部位中分离制备了14个单体，包括11个(口山)酮甙元，其中7个为首次从抱茎獐牙菜中分离得到。从药材正丁醇萃取部位中分离表征了24个化合物，其中包括2个新(口山)酮甙和2个新环烯醚萜甙，有4个环烯醚萜甙、7个(口山)酮甙、1个黄酮甙及赤矢车菊素为首次从抱茎獐牙菜中分离到。用HPLC-UV-MS技术对分离到的一个环烯醚萜组分进行了在线分析表征，推测了其中两个微量新环烯醚萜甙的结构。
用单扫描示波极谱法和荧光分光光度法测定了Bellidifolin等5种(口山)酮甙元的抗自由基作用，结果均表现出较强的抑制超氧阴离子自由基和羟基自由基作用。通过缺血性脑损伤动物模型的药理研究，首次发现Bellidifolin具有较强的脑保护作用，显示了良好的应用前景。论文还归纳总结了天然氧代(口山)酮及其甙类化合物的~1H和~(13)C核磁共振谱学规律，为(口山)酮类化合物的核磁共振表征提供了理论依据。
'Zang-Yin-Chen' ( ZYC) is a traditional Tibetan medicine for the treatment of hepatitis and cholecystitis. The plant Swertia franchetiana Smith (family Gentianaceae) is distributed in Qinghai-Tibet Plateau and used as plant materials of ZYC. In order to clarify the chemical foundation of this herb, the dissertation describes the preparation, isolation and characterization of bioactive principles from S. franchetiana. The main research results are as follows:
The methanol crude extract of ZYC was screened by means of combined HPLC-UV-MS technique. The structural information was obtained from on-line UV and MS spectra at the early stage of preparative isolation. Phytochemical investigation of liposoluble fractions of the methanol extracts led to the isolation of fourteen pure compounds including eleven xanthone aglycones, of which seven compounds were isolated from this plant for the first time. Additional twenty-four compounds were isolated and characterized from n-BuOH fractions of methanol extracts from ZYC. Among them, two new iridoid glycosides and two new xanthone glycosides were obtained by means of preparative HPLC. The other 4 iridoid glycosides and 7 xanthone glycosides, together with isovitexin and erythrocentaurin, were all firstly found from this plant. Besides, two minor compounds from an aqueous fraction were tentatively identified as two new iridoid glycosides by means of HPLC-UV-MS analysis.
Five xanthones from this plant were tested for the properties of radical scavenging by means of oscillopolarography and fluorescent spectrophotometry, and showed
capacity to scavenge both superoxide anion radical and hydroxyl radical. Bellidifolin was further tested for the protective activity on cerebral-ischemia animals in vivo. The results revealed that Bellidifolin possessed potent brain-protective activity and showed prospects of pharmaceutical application.
The 1H and 13C NMR data of natural xanthones from ZYC and literatures were analyzed and summarized. Some rules of 1H and 13C chemical shifts were deduced in order to supply a theoretic reference for the NMR characterization of natural xanthone compounds.
引文
1．杨永昌，《藏药志》，青海人民出版社，1991：111
2．罗达尚，《中华藏本草》，民族出版社，1997：187
3．李福银，丁经业，“藏药藏茵陈系列治疗肝炎的进展”，中国药房，1995，6(3)：38-39
4．谭桂山，徐平声，田华咏等，“川东獐牙菜化学成分的研究”，中国药学杂志，2000，35
(7)：441-443
5．王芸，杨峻山，“獐牙菜属植物的研究概况”，天然产物研究与开发，1992(3)：99-114
6．梁巨忠，“小儿腹痛草有效成分獐牙菜苦甙的分离和鉴定”，药学通报，1982，17(4)：242—243
7. K. Hase, JX Li, P.Basnet et al, "Hepatoprotective principles of Swartia japonica on D-Galactosamaine/Lipopolysaecharide induced liver injury in mice", Chem Pharm Bull, 1997, 45(11):1823-1827
8. N Pant, DC Jain, RS Bhakuni, "Phytochemicals from genus Swertia and their biological activities", Indian Journal of Chemistry, 2000, 39B: 565-586
9．陈家春，万定荣，难波恒雄，“獐牙属民族民间药物的整理”，中国民族民间药物杂志，1999，37，98-101
10．中国科学院植物志编辑委员会，《中国植物志》，科学出版社，1988：353-411
11．淮虎银，郭继明，胡芳弟。“国产獐牙菜属药用植物资源”，甘肃科学学报，1995，7(4)：29-32
12．宋万志，“中国龙胆科药用植物概况”，中药通报，1986，11(1)：643-647
13. S Rodriguez, A Marston, JL Wolfender. "Iridoids and secoiridoids in the Gentianaceae", Curr. Org. Chem., 1987, 2(6): 627-648.
14. DL Dreyer, JH Bourell. "Xanthones of the Gentianaceae", Phytochemistry, 1981, 20(3):493-495.
15．谭沛，刘永隆，“植物咄酮甙类化合物”，天然产物研究与开发，1995，3：45-54
16．王宁，周乐，“龙胆属植物化学成分研究概况”，山西林业科技，2001，3：71-78
17．姜燕，“獐牙菜属植物化学成分的研究概况“，外国医药植物药分册，1990，5(3)：99-103
18. S Mandal, A Chatterjee, "Strucfure of chiratanin, a novel dimeric xanthone", Tetrahedron Letters, 1987, 28(12): 1309-1310.
19. HM zhou, YL Liu, G Blasko, et al, "Swertiabisxanthcne-I from Swertia Macrosperma", phytochemistry, 1989, 28(12): 3569-3571
20. P Tan, CY Hou, YL Liu, et al, "Swertipunicoside, the frist bisxanthone C-glycoside". J org, chem, 1991, 56: 7130-7133
21. P Tan, CY Hou, YL Liu, et al, "3-Demethyl-swertipunicoside from Swertia punicea", Phytochemistry, 1992;31(12): 4313-15
22. S Mandal, PC Dos, PC Joshi, et al,"Anti-inflammatory action of swertia chirata"
Fitoterapia, 1992,63(2): 122-8
23. K Hase, S Kadota, P Basnet, et al, "Tetrahydroswertianolin: a potent hepatoprotective agent from Swerhia japoniea Makino", Chem Pharm Bull 45(3): 567-569
24．丁经业，樊淑芬，“抱茎獐牙菜(口山)酮成分分离与鉴定”，高原生物药集刊，1982，1：267-270
25．郭信芳，“川东獐牙菜中的龙胆(口山)酮的分离和结构鉴定”，中草药，1980，11(5)：200
26. KS Khetwal, B Joshi, RS Bishet,. "Tri- and tetraoxygenated xanthones from Swertia petiolata", Phytochemistry, 1990, 29(4): 1265-1267.
27. S Ghosal, K Bismas, DK Jaiswal, "Xanthone and flavonol constituents of Swertia Hookeri. Phytochemistry", 1980, 19(1): 123-6
28. A Prakash, PC Basumafary, S Ghosal. "Chemical constituents of Swertia panicalata" Planta Med. 1982, 45(1): 61-2
29．孙洪发，丁经业，“川西獐牙菜中(口山)酮成分的分离和鉴定”，植物学报，1981，23(6)，464-9
30．王建农，候翠英，“抱茎獐牙菜化学成分的研究”，中草药，1994，25(8)：401-403
31．潘莉，张晓峰，王明奎，“祁连獐牙菜化学成分研究”，中草药，2002，33(7)：583-586
32．胡伯村，丁经业，孙洪发等，“祁连獐牙菜化学成分”，植物学报，1991，33(7)，507-510
33．廖志新，胡柏林，经兰菊，“轮叶獐牙菜的化学成分研究”，植物学报，1991，33(12)：968-970
34. KK Asthana, NK Sharma, PK Kuishreshtho. "A xanthone from Swertia chirayita" Phytochemistry, 1991, 30(3): 1037-1039.
35．胡伯村，孙洪发，樊淑芬，“红直獐牙菜的(口山)酮成分”，植物学报，1992，34(11)：886-888
36. F Narihiko, O Masayoshi, "Xanthones from Swertia punicea", Journal of Natural Products,1990,53(6): 1543-1547
37．何仁远，聂瑞麟，“青叶胆中(口山)酮成分的分离和鉴定”，云南植物研究，1982，4(1)：68
38. A Rahamn, A Pervin, M Feroz, "Phytochemical studies on Swertia cordata", Journal of Natural Products, 1994, 57(1): 134-137.
39. P Kulanthaivel, SW Pelletier, KS Khetwal. "Isolation of a new xanthone and 2-hydroxy-dimethyl-terephthalate from Swertia petiolata", Journal of Natural Products, 1988, 51(2): 379-381.
40．刘嘉森，黄梅芬，“青叶胆中(口山)酮成分的分离与鉴定”，中草药，1982，13(10)：433—434
41. H Xiao, ZN Chen, GM Liu, et al. "A new xanthone from Swertia decora", Molecules, 2000,
5:M181.
42．肖怀，陆阳，陈乃泽，“观赏獐牙菜中新(口山)酮的化学成分研究”，中国药学杂志，2001，36(5)：302-304
43．谭桂山，徐康平，徐平声，“川东獐牙菜化学成分研究”，药学学报，2002，37(8)：630-632
44．孔德云，蒋毅，姚英，等。“伸梗獐牙菜的甙类成分”，中草药，1995，26(1)：7-10．
45．丁经业，樊淑芬，胡伯林。“抱茎獐牙菜的(口山)酮甙和黄酮甙”，植物学报，1988，30(4)：414-419．
46．孙洪发，胡伯林，丁经业。“川西獐牙菜的甙类成分”，植物学报，1991，33(4)：31-37．
47. KS Khetwal, RS Bisht. "A xanthone glycoside from Swertia speciosa", Phytochemistry, 1988, 27(6): 1910-11.
48. I Sakamoto, T Tanaka, O Tanaka. "Xanthone glucosides of Swertia japonica and a related plant", Chem Pharm Bull, 1982, 30(11): 4088-4091
49．卞庆亚，侯翠英，陈建民，“抱萼獐牙菜的化学成分研究”，天然产物研究与开发，1996，10(1)：1-5
50．李玉林，丁晨旭，刘健全，等。“红直獐牙菜的苷类成分”，中草药，2002，33(2)：104-106．
51. "A new xanthone glucopyranoside from Swertia ciliata", CA abstract, 134: 277953.
52. "A xanthone dixylopyranoside from Swertia thomsoni", CA abstract, 136: 398543.
53. N Menkovic, SF Kafarina, B Vainja. "Xanthones from Swertia punctata", Phytochemistry, 2002, 61:415-420.
54. ZX Liao, YL Li, MK Wang, et al. "Two new xanthone glycosides from Swertia tetraptera", Chinese Chemical Letters, 2001, 12(5): 433-434.
55. JN Wang, CY Hou, YL Liu. "Swertiafrancheside, An HIV-reverse transcriptase inhibitor and the first flavone-xanthone Dimer from Swertia franchetiana", Journal of Natural Products, 1994, 57(2): 211-247.
56. H Kikazaki, Y Kavasaki, S Kitamura. "Secoiridoid glucosids from Swertia mileensis", Planta Med, 1996, 62: 35-38.
57．罗跃华，聂瑞麟。“狭叶獐牙菜中的两个新环烯醚萜甙”，药学学报，1992，27(2)：125-129．
58．罗跃华，聂瑞麟。“显脉獐牙菜的单萜环烯醚萜甙”，植物学报，1993，35(4)：307-310．
59．谭沛，刘永漋，侯翠英，“紫红獐牙菜中紫药苦甙的结构”，药学学报，1993，28(7)：522-525．
60. Y Ikeshiro,Y Tomita. "A new iridoid glucoside of Swertia japonica", Planta Med, 1984,
50(6): 485-488.
61. Y Ikeshiro, Y Tomita. "Iridoid glucoside ofSwertia japonica", Planta Med, 1985, 51(5): 390-393.
62. Y Ikeshiro, Y Tomita. "Senburiside Ⅱ, a new iridoid glucoside of Swertia japonica", Planta Med, 1987, 53(2): 158-161.
63. S Bhan, R Kumar, AK Kalla. "Isomeric 2,3-secohopene lactones from Swertia petiolata", Phytochemistry, 1987, 26(12): 3363-3364.
64. Bham S, Kumar R, Kalla AK, et al. "Triterpenoids from Swertia petiolata", Phytochemistry, 1988, 27(2): 539-542.
65. I Kanji, S Hiroshi, S Motoyoshi, et al. "Phenyl glucosides from a hairy root culture of Swertia japonica", Phytochemistry, 1990, 29(12): 3823-3825.
66. AK Chakravarity, D Binayaku. "Chiratenol, a novel rearranged lopane triperpenoid from Swertia chirata", Tetrahedron letters, 1990, 31(52): 7649-7652.
67. AK Chakravarity, S Mukhopadhyay. "Kairatenol, yet another novel migrated gammacerane triperpenoid from Swertia chirata", Tetrahedron letters, 1992, 33(1): 125-126.
68．王宪楷，《天然药物化学》，人民卫生出版社，1988：404。
69. AK Chakravarty, S Mukhopadhyay, SK Moitra. "(-)syringaresinol, a hepatoprotective agent and other constituents from Swertia chirata", Indian J. Chem. (B), 1994, 33B(4): 405-408.
70. T Sakai, Y Nakagawa, T Iwashita. "The structures of semburin and isosemburin, 2,8-dioxabicyclo[3,3,1] nonanes isolated from Swertia japonica", Chem. Lett., 1981, 9: 1257-1258.
71. T Sakai, Y Nakagawa, T Iwashita. "Semburins and Swertiols, novel 2,8- dioxabicyclo[3,3,1] nonanes and their precursor alcohols from Swertia japonica", Bull. Chem. Soc. Jpn., 1983, 51(11): 3477-3482.
72. S Rodriguez, JL Wolfender, E Hakizamurgu. "An antifungal naphthoquinone, xanthones and secoiridoids from Swertia calycina", Pianta medica, 1995, 61(4): 362-364.
73．张俊巍，茅青，“西南獐牙菜化学成分的研究”，药学学报，1984，19(11)：819-824．
74. M Karan. "Activity of Swertia chirata against paracetamol and D-Galactosamine-induced liver injury in rats", Phytother. Res., 1999, 13(2): 95-101.
75. PK Reen, M Karan, K Singh, et al. "Screening of various Swertia species extracts in primary monolayer cultures of rat hepatocytes against CCl_4 and paracetamol-induced toxicity", J
Ethnopharmacology, 2001,75:239-247.
76．杜继曾，李庆芬，陈晓光。“川西獐牙菜对低张性低氧肝损伤的保护作用”，药学学报，1983，18(3)：174-178．
77. H Hikino, Y Kiso, M Kubota. "Antihepatotoxic principles of Swertia japonica", CA Abstract 103: 154067.
78. K Hase, QB Xiong, P Basnet, et al. "Inhibitory effect of tetrahydroswertianolin on tumor necrosis factor-α-dependent hepatic apoptosis in mice", Biochemical Pharmacology, 1999, 57: 1431-1437.
79．丁经业，孙洪发，“藏茵陈抗肝炎有效成分研究—芒果甙和齐墩果酸的分离和鉴定”，中草药，1980，11(9)：391-392．
80．卞庆亚，“芒果甙对实验性肝损伤大鼠酶及形态变化影响的研究”，中国实验动物学杂志，1999，9(1)：10-13．
81. " Xanthone glycosides in Gentianaceae of Qinghai-Tibet Plateau". CA abstract, 131:16414.
82．刘占文，陈长勤，金若敏，等。“龙胆苦甙的保肝作用研究”，中草药，2002，33(1)：47-50．
83. B Chandrasekar, MB Bajpai, SK Mukherjee. "Hypoglycemic activity of Swertia chirayita", Indian J Exp. Biol. 1990, 28(7): 616-618.
84. AM Saxena, MB Bajpai, SK Mukherjee. "Swerchirin induced blood sugar lowering of streptozotocin treated by hyperglycemic rats", Indian J Exp. Biol., 1991, 29(7): 674-675.
85. MB Bajpai, RK Asthana, NK Sharma. "Hypoglycemic effect of swerchirin from the hexane fraction of Swertia chirayita", Planta Med., 1991, 57(2): 102-104.
86. AM Saxena, MB Bajpai, PS Murthy. "Mechanism of blood sugar lowering by a hexane fraction of Swertia chirayita", Indian J Exp. Biol., 1993, 31(2): 178-181.
87. P Basnet, S Kadota, M Shimizu. "Bellidifolin: a potent hypoglycemic agent in streptozotocin (STZ)-induced diabetic rats from Swertia joponica", Planta med., 1994, 60(6): 507-511.
88. P Basnet, S Kadota, m Shimizu. "Bellidifolin stimulates glucose uptake in rat fibroblasts and ameliorates hyperglycemia in STZ-induced diabetic rats", Planta med., 1995, 61(5): 402-405.
89. T Nanba, M Shimizu, S Kadota. "Hypoglycemics containing bellidifolin analogs",日本专利: JP07206673A2 8 Aug 1995 heisei 8pp
90. J Yamakara, M Kobayashi, H Matsuda. "Anticholinergic action of Swertia japonica and an active constituent", J Ethnopharmacol, 1991,33(1): 31-35.
91. "Pharmacological actions of Swertia japonica extracts, swertiamarin and gentianine", CA
abstract, 90:115084.
92. S Rafatullah, M Tariq, JS Mossa. "Protective effect of Swertia chirata against indomethacin and other ulcerogenic agent-induced gastric ulcers", Drugs Exp. Clin. Res., 1993, 19(2): 69-73.
93. "Antiinflammatory secoiridoids". CA abstract, 91: 9485.
94. N Ramesh, MB Viswanathan, A Saraswathy. "Antimicrobial and phytochemical studies of Swertia corymbosa", Fitoterapia, 2002, 73: 160-164.
95. "Antimicrobial potential of some xanthones from Swertia ciliata". CA, abstract 131: 127505.
96. S Ashida, SF Noguchi, T Suzuki. "Antioxidative components, xanthone derivatives in Swertia japonica", J AM. Oil. Chem. Soc., 1994, 71(10): 1095-1099.
97. O Nobuko, S Takehiko, O Tomio. "Xanthone derives as inhibitors for monoamine oxidase", Journal of Molecular Catalysis B: Enzymatic, 2000, 10:291-294.
98. S Ray, HK Majumder, AK Chakravarty. "Amarogentin, a naturally occurring secoiridoid glycoside, and a newly recognized inhibitor of Topoisomerase I from Leishmania donovani", Journal of Natural Products, 1996, 59(1): 27-29.
99. "Evaluation of the in-vivo activity and toxicity of amarogentin, an antileishmanial agent in both liposomal and niosomal forms". CA abstract, 132:131834.
100．《中药辞海》，中国医药科技出版社，1996：900-901。
101．何泉华，邓芹英。“1,8-2羟基-3,5-二甲氧基(口山)酮对缺血再灌脑内氨基酸乙酰胆碱酯酶活性的影响”，中草药，2001，32(2)：147-149．
103．何泉华，许实波。“(口山)酮对大鼠心肌线粒体氧化损伤的保护作用”，中国药学杂志，2000，35(6)：381-383．
104. DJ Jiang, GS Tan, ZH Zhou. "Protective effect of demethybellidifolin on myocardial ischemia-reperfusion injury in rats", Planta Med., 2002, 68(8): 710-713.
105. RW Winter, PB Hans. "Xanthones as antimalarial agents", FEBS Letters, 1997, 409: 67-73.
106．肖怀，陆阳，陈泽乃，等。“獐牙菜属植物的化学和药理研究进展”，中草药，1999，30(增刊)：36-40。
107．胡西白合提，哈斯也提，陈俊逾。“藏茵陈胶囊治疗病毒炎肝炎80例”，新疆中医药，2001，19(增刊)：28—29。
108．徐志杰。“獐牙菜属药用植物的研究概况”，江西中医药，1989(4)：60-61．
2．罗达尚，《中华藏本草》，民族出版社，1997：187
3．李福银，丁经业，“藏药藏茵陈系列治疗肝炎的进展”，中国药房，1995，6(3)：38-39
4．谭桂山，徐平声，田华咏等，“川东獐牙菜化学成分的研究”，中国药学杂志，2000，35
(7)：441-443
5．王芸，杨峻山，“獐牙菜属植物的研究概况”，天然产物研究与开发，1992(3)：99-114
6．梁巨忠，“小儿腹痛草有效成分獐牙菜苦甙的分离和鉴定”，药学通报，1982，17(4)：242—243
7. K. Hase, JX Li, P.Basnet et al, "Hepatoprotective principles of Swartia japonica on D-Galactosamaine/Lipopolysaecharide induced liver injury in mice", Chem Pharm Bull, 1997, 45(11):1823-1827
8. N Pant, DC Jain, RS Bhakuni, "Phytochemicals from genus Swertia and their biological activities", Indian Journal of Chemistry, 2000, 39B: 565-586
9．陈家春，万定荣，难波恒雄，“獐牙属民族民间药物的整理”，中国民族民间药物杂志，1999，37，98-101
10．中国科学院植物志编辑委员会，《中国植物志》，科学出版社，1988：353-411
11．淮虎银，郭继明，胡芳弟。“国产獐牙菜属药用植物资源”，甘肃科学学报，1995，7(4)：29-32
12．宋万志，“中国龙胆科药用植物概况”，中药通报，1986，11(1)：643-647
13. S Rodriguez, A Marston, JL Wolfender. "Iridoids and secoiridoids in the Gentianaceae", Curr. Org. Chem., 1987, 2(6): 627-648.
14. DL Dreyer, JH Bourell. "Xanthones of the Gentianaceae", Phytochemistry, 1981, 20(3):493-495.
15．谭沛，刘永隆，“植物咄酮甙类化合物”，天然产物研究与开发，1995，3：45-54
16．王宁，周乐，“龙胆属植物化学成分研究概况”，山西林业科技，2001，3：71-78
17．姜燕，“獐牙菜属植物化学成分的研究概况“，外国医药植物药分册，1990，5(3)：99-103
18. S Mandal, A Chatterjee, "Strucfure of chiratanin, a novel dimeric xanthone", Tetrahedron Letters, 1987, 28(12): 1309-1310.
19. HM zhou, YL Liu, G Blasko, et al, "Swertiabisxanthcne-I from Swertia Macrosperma", phytochemistry, 1989, 28(12): 3569-3571
20. P Tan, CY Hou, YL Liu, et al, "Swertipunicoside, the frist bisxanthone C-glycoside". J org, chem, 1991, 56: 7130-7133
21. P Tan, CY Hou, YL Liu, et al, "3-Demethyl-swertipunicoside from Swertia punicea", Phytochemistry, 1992;31(12): 4313-15
22. S Mandal, PC Dos, PC Joshi, et al,"Anti-inflammatory action of swertia chirata"
Fitoterapia, 1992,63(2): 122-8
23. K Hase, S Kadota, P Basnet, et al, "Tetrahydroswertianolin: a potent hepatoprotective agent from Swerhia japoniea Makino", Chem Pharm Bull 45(3): 567-569
24．丁经业，樊淑芬，“抱茎獐牙菜(口山)酮成分分离与鉴定”，高原生物药集刊，1982，1：267-270
25．郭信芳，“川东獐牙菜中的龙胆(口山)酮的分离和结构鉴定”，中草药，1980，11(5)：200
26. KS Khetwal, B Joshi, RS Bishet,. "Tri- and tetraoxygenated xanthones from Swertia petiolata", Phytochemistry, 1990, 29(4): 1265-1267.
27. S Ghosal, K Bismas, DK Jaiswal, "Xanthone and flavonol constituents of Swertia Hookeri. Phytochemistry", 1980, 19(1): 123-6
28. A Prakash, PC Basumafary, S Ghosal. "Chemical constituents of Swertia panicalata" Planta Med. 1982, 45(1): 61-2
29．孙洪发，丁经业，“川西獐牙菜中(口山)酮成分的分离和鉴定”，植物学报，1981，23(6)，464-9
30．王建农，候翠英，“抱茎獐牙菜化学成分的研究”，中草药，1994，25(8)：401-403
31．潘莉，张晓峰，王明奎，“祁连獐牙菜化学成分研究”，中草药，2002，33(7)：583-586
32．胡伯村，丁经业，孙洪发等，“祁连獐牙菜化学成分”，植物学报，1991，33(7)，507-510
33．廖志新，胡柏林，经兰菊，“轮叶獐牙菜的化学成分研究”，植物学报，1991，33(12)：968-970
34. KK Asthana, NK Sharma, PK Kuishreshtho. "A xanthone from Swertia chirayita" Phytochemistry, 1991, 30(3): 1037-1039.
35．胡伯村，孙洪发，樊淑芬，“红直獐牙菜的(口山)酮成分”，植物学报，1992，34(11)：886-888
36. F Narihiko, O Masayoshi, "Xanthones from Swertia punicea", Journal of Natural Products,1990,53(6): 1543-1547
37．何仁远，聂瑞麟，“青叶胆中(口山)酮成分的分离和鉴定”，云南植物研究，1982，4(1)：68
38. A Rahamn, A Pervin, M Feroz, "Phytochemical studies on Swertia cordata", Journal of Natural Products, 1994, 57(1): 134-137.
39. P Kulanthaivel, SW Pelletier, KS Khetwal. "Isolation of a new xanthone and 2-hydroxy-dimethyl-terephthalate from Swertia petiolata", Journal of Natural Products, 1988, 51(2): 379-381.
40．刘嘉森，黄梅芬，“青叶胆中(口山)酮成分的分离与鉴定”，中草药，1982，13(10)：433—434
41. H Xiao, ZN Chen, GM Liu, et al. "A new xanthone from Swertia decora", Molecules, 2000,
5:M181.
42．肖怀，陆阳，陈乃泽，“观赏獐牙菜中新(口山)酮的化学成分研究”，中国药学杂志，2001，36(5)：302-304
43．谭桂山，徐康平，徐平声，“川东獐牙菜化学成分研究”，药学学报，2002，37(8)：630-632
44．孔德云，蒋毅，姚英，等。“伸梗獐牙菜的甙类成分”，中草药，1995，26(1)：7-10．
45．丁经业，樊淑芬，胡伯林。“抱茎獐牙菜的(口山)酮甙和黄酮甙”，植物学报，1988，30(4)：414-419．
46．孙洪发，胡伯林，丁经业。“川西獐牙菜的甙类成分”，植物学报，1991，33(4)：31-37．
47. KS Khetwal, RS Bisht. "A xanthone glycoside from Swertia speciosa", Phytochemistry, 1988, 27(6): 1910-11.
48. I Sakamoto, T Tanaka, O Tanaka. "Xanthone glucosides of Swertia japonica and a related plant", Chem Pharm Bull, 1982, 30(11): 4088-4091
49．卞庆亚，侯翠英，陈建民，“抱萼獐牙菜的化学成分研究”，天然产物研究与开发，1996，10(1)：1-5
50．李玉林，丁晨旭，刘健全，等。“红直獐牙菜的苷类成分”，中草药，2002，33(2)：104-106．
51. "A new xanthone glucopyranoside from Swertia ciliata", CA abstract, 134: 277953.
52. "A xanthone dixylopyranoside from Swertia thomsoni", CA abstract, 136: 398543.
53. N Menkovic, SF Kafarina, B Vainja. "Xanthones from Swertia punctata", Phytochemistry, 2002, 61:415-420.
54. ZX Liao, YL Li, MK Wang, et al. "Two new xanthone glycosides from Swertia tetraptera", Chinese Chemical Letters, 2001, 12(5): 433-434.
55. JN Wang, CY Hou, YL Liu. "Swertiafrancheside, An HIV-reverse transcriptase inhibitor and the first flavone-xanthone Dimer from Swertia franchetiana", Journal of Natural Products, 1994, 57(2): 211-247.
56. H Kikazaki, Y Kavasaki, S Kitamura. "Secoiridoid glucosids from Swertia mileensis", Planta Med, 1996, 62: 35-38.
57．罗跃华，聂瑞麟。“狭叶獐牙菜中的两个新环烯醚萜甙”，药学学报，1992，27(2)：125-129．
58．罗跃华，聂瑞麟。“显脉獐牙菜的单萜环烯醚萜甙”，植物学报，1993，35(4)：307-310．
59．谭沛，刘永漋，侯翠英，“紫红獐牙菜中紫药苦甙的结构”，药学学报，1993，28(7)：522-525．
60. Y Ikeshiro,Y Tomita. "A new iridoid glucoside of Swertia japonica", Planta Med, 1984,
50(6): 485-488.
61. Y Ikeshiro, Y Tomita. "Iridoid glucoside ofSwertia japonica", Planta Med, 1985, 51(5): 390-393.
62. Y Ikeshiro, Y Tomita. "Senburiside Ⅱ, a new iridoid glucoside of Swertia japonica", Planta Med, 1987, 53(2): 158-161.
63. S Bhan, R Kumar, AK Kalla. "Isomeric 2,3-secohopene lactones from Swertia petiolata", Phytochemistry, 1987, 26(12): 3363-3364.
64. Bham S, Kumar R, Kalla AK, et al. "Triterpenoids from Swertia petiolata", Phytochemistry, 1988, 27(2): 539-542.
65. I Kanji, S Hiroshi, S Motoyoshi, et al. "Phenyl glucosides from a hairy root culture of Swertia japonica", Phytochemistry, 1990, 29(12): 3823-3825.
66. AK Chakravarity, D Binayaku. "Chiratenol, a novel rearranged lopane triperpenoid from Swertia chirata", Tetrahedron letters, 1990, 31(52): 7649-7652.
67. AK Chakravarity, S Mukhopadhyay. "Kairatenol, yet another novel migrated gammacerane triperpenoid from Swertia chirata", Tetrahedron letters, 1992, 33(1): 125-126.
68．王宪楷，《天然药物化学》，人民卫生出版社，1988：404。
69. AK Chakravarty, S Mukhopadhyay, SK Moitra. "(-)syringaresinol, a hepatoprotective agent and other constituents from Swertia chirata", Indian J. Chem. (B), 1994, 33B(4): 405-408.
70. T Sakai, Y Nakagawa, T Iwashita. "The structures of semburin and isosemburin, 2,8-dioxabicyclo[3,3,1] nonanes isolated from Swertia japonica", Chem. Lett., 1981, 9: 1257-1258.
71. T Sakai, Y Nakagawa, T Iwashita. "Semburins and Swertiols, novel 2,8- dioxabicyclo[3,3,1] nonanes and their precursor alcohols from Swertia japonica", Bull. Chem. Soc. Jpn., 1983, 51(11): 3477-3482.
72. S Rodriguez, JL Wolfender, E Hakizamurgu. "An antifungal naphthoquinone, xanthones and secoiridoids from Swertia calycina", Pianta medica, 1995, 61(4): 362-364.
73．张俊巍，茅青，“西南獐牙菜化学成分的研究”，药学学报，1984，19(11)：819-824．
74. M Karan. "Activity of Swertia chirata against paracetamol and D-Galactosamine-induced liver injury in rats", Phytother. Res., 1999, 13(2): 95-101.
75. PK Reen, M Karan, K Singh, et al. "Screening of various Swertia species extracts in primary monolayer cultures of rat hepatocytes against CCl_4 and paracetamol-induced toxicity", J
Ethnopharmacology, 2001,75:239-247.
76．杜继曾，李庆芬，陈晓光。“川西獐牙菜对低张性低氧肝损伤的保护作用”，药学学报，1983，18(3)：174-178．
77. H Hikino, Y Kiso, M Kubota. "Antihepatotoxic principles of Swertia japonica", CA Abstract 103: 154067.
78. K Hase, QB Xiong, P Basnet, et al. "Inhibitory effect of tetrahydroswertianolin on tumor necrosis factor-α-dependent hepatic apoptosis in mice", Biochemical Pharmacology, 1999, 57: 1431-1437.
79．丁经业，孙洪发，“藏茵陈抗肝炎有效成分研究—芒果甙和齐墩果酸的分离和鉴定”，中草药，1980，11(9)：391-392．
80．卞庆亚，“芒果甙对实验性肝损伤大鼠酶及形态变化影响的研究”，中国实验动物学杂志，1999，9(1)：10-13．
81. " Xanthone glycosides in Gentianaceae of Qinghai-Tibet Plateau". CA abstract, 131:16414.
82．刘占文，陈长勤，金若敏，等。“龙胆苦甙的保肝作用研究”，中草药，2002，33(1)：47-50．
83. B Chandrasekar, MB Bajpai, SK Mukherjee. "Hypoglycemic activity of Swertia chirayita", Indian J Exp. Biol. 1990, 28(7): 616-618.
84. AM Saxena, MB Bajpai, SK Mukherjee. "Swerchirin induced blood sugar lowering of streptozotocin treated by hyperglycemic rats", Indian J Exp. Biol., 1991, 29(7): 674-675.
85. MB Bajpai, RK Asthana, NK Sharma. "Hypoglycemic effect of swerchirin from the hexane fraction of Swertia chirayita", Planta Med., 1991, 57(2): 102-104.
86. AM Saxena, MB Bajpai, PS Murthy. "Mechanism of blood sugar lowering by a hexane fraction of Swertia chirayita", Indian J Exp. Biol., 1993, 31(2): 178-181.
87. P Basnet, S Kadota, M Shimizu. "Bellidifolin: a potent hypoglycemic agent in streptozotocin (STZ)-induced diabetic rats from Swertia joponica", Planta med., 1994, 60(6): 507-511.
88. P Basnet, S Kadota, m Shimizu. "Bellidifolin stimulates glucose uptake in rat fibroblasts and ameliorates hyperglycemia in STZ-induced diabetic rats", Planta med., 1995, 61(5): 402-405.
89. T Nanba, M Shimizu, S Kadota. "Hypoglycemics containing bellidifolin analogs",日本专利: JP07206673A2 8 Aug 1995 heisei 8pp
90. J Yamakara, M Kobayashi, H Matsuda. "Anticholinergic action of Swertia japonica and an active constituent", J Ethnopharmacol, 1991,33(1): 31-35.
91. "Pharmacological actions of Swertia japonica extracts, swertiamarin and gentianine", CA
abstract, 90:115084.
92. S Rafatullah, M Tariq, JS Mossa. "Protective effect of Swertia chirata against indomethacin and other ulcerogenic agent-induced gastric ulcers", Drugs Exp. Clin. Res., 1993, 19(2): 69-73.
93. "Antiinflammatory secoiridoids". CA abstract, 91: 9485.
94. N Ramesh, MB Viswanathan, A Saraswathy. "Antimicrobial and phytochemical studies of Swertia corymbosa", Fitoterapia, 2002, 73: 160-164.
95. "Antimicrobial potential of some xanthones from Swertia ciliata". CA, abstract 131: 127505.
96. S Ashida, SF Noguchi, T Suzuki. "Antioxidative components, xanthone derivatives in Swertia japonica", J AM. Oil. Chem. Soc., 1994, 71(10): 1095-1099.
97. O Nobuko, S Takehiko, O Tomio. "Xanthone derives as inhibitors for monoamine oxidase", Journal of Molecular Catalysis B: Enzymatic, 2000, 10:291-294.
98. S Ray, HK Majumder, AK Chakravarty. "Amarogentin, a naturally occurring secoiridoid glycoside, and a newly recognized inhibitor of Topoisomerase I from Leishmania donovani", Journal of Natural Products, 1996, 59(1): 27-29.
99. "Evaluation of the in-vivo activity and toxicity of amarogentin, an antileishmanial agent in both liposomal and niosomal forms". CA abstract, 132:131834.
100．《中药辞海》，中国医药科技出版社，1996：900-901。
101．何泉华，邓芹英。“1,8-2羟基-3,5-二甲氧基(口山)酮对缺血再灌脑内氨基酸乙酰胆碱酯酶活性的影响”，中草药，2001，32(2)：147-149．
103．何泉华，许实波。“(口山)酮对大鼠心肌线粒体氧化损伤的保护作用”，中国药学杂志，2000，35(6)：381-383．
104. DJ Jiang, GS Tan, ZH Zhou. "Protective effect of demethybellidifolin on myocardial ischemia-reperfusion injury in rats", Planta Med., 2002, 68(8): 710-713.
105. RW Winter, PB Hans. "Xanthones as antimalarial agents", FEBS Letters, 1997, 409: 67-73.
106．肖怀，陆阳，陈泽乃，等。“獐牙菜属植物的化学和药理研究进展”，中草药，1999，30(增刊)：36-40。
107．胡西白合提，哈斯也提，陈俊逾。“藏茵陈胶囊治疗病毒炎肝炎80例”，新疆中医药，2001，19(增刊)：28—29。
108．徐志杰。“獐牙菜属药用植物的研究概况”，江西中医药，1989(4)：60-61．