柠条籽镇痛及抗肿瘤物质基础研究
摘要
根据国际疼痛研究会(IASP)对疼痛的定义:“一种不愉快的感觉和实际的或潜在的组织损伤所引发的情感经历;或者就这一损伤所做的描述”,疼痛属于一种不愉快的生理体验,它广泛出现于各种疾病的病程中,是临床上最常见的症状。由于外来的伤害或自身的病变,任何人的一生都难免疼痛,其中疼痛较重又不能自行缓解而需要就医者约占全人群的1/10。疼痛,特别是剧烈的或持久性疼痛,常使患者遭受种种痛苦,如惊慌、害怕、焦虑、悲伤、愤怒、烦躁、失眠,进而影响机体局部甚至整体的功能,严重者还可以导致生理功能紊乱,引发疼痛性休克。因此合理应用镇痛药,有效地控制疼痛十分重要,这不仅能解除患者痛苦,改善患者的生活质量,同时给他们心理极大的安慰,加强同疾病作斗争的信心。
目前用于疼痛治疗的药物主要有四类:一类是阿片类镇痛药,具有成瘾性;一类是作用于中枢的非阿片类镇痛药,但无抗炎抗风湿作用,并具有肝毒性;一类是作用于外周的抗炎镇痛药,但长期服用容易引起胃肠损害。一类是复方抗炎镇痛药,但由于联合用药机制的复杂性,该类药物还很少,而且安全性也需要进一步长期观察。
因此目前临床上仍缺乏理想的镇痛药物。近年来国内外对从天然药物中寻找新的镇痛成分研究十分活跃,从天然药物中寻找高效、低毒、无依赖性的镇痛新药将成为主流的发展趋势,已有用于临床的报道,如延胡索乙素、辣椒素等。
柠条籽是豆科锦鸡儿属植物小叶锦鸡儿(Caragana microphylla Lam.)的成熟种子,同时在不同地区也将中间锦鸡儿和树锦鸡儿的成熟种子作为柠条籽入药。其原植物生长于欧亚大陆干旱半干旱地区,主产于我国东北、华北、西北和西南各省区,我国产62种,大多数作为绿化及防风固沙植物,仅有少数应用于药用。柠条籽味苦,性寒。清热利咽,主治咽喉肿痛等症。
国内学者研究表明,锦鸡儿属植物中含有黄酮、二苯乙烯低聚体、三萜、生物碱等化学成分,但反映柠条籽临床功效与药理作用的有效成分有待阐明。目前柠条籽药材尚未被药典收载,且对于其原植物的植物分类学尚存在较大的争议。我们在内蒙古呼和浩特市采集柠条籽,将柠条籽75%乙醇浸膏用水混悬,依次用石油醚、氯仿、乙酸乙酯、正丁醇萃取,分成石油醚、氯仿、乙酸乙酯、正丁醇、水共5个极性部位,并对各部位进行了初步药效学试验,结果表明,柠条籽的总提物、石油醚及氯仿部位(1g
In accordance with the International Association for the Study of Pain, pain has been defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. The pain appears widely in various kinds of diseases in clinic. Thousands of patients with intense and unrelenting pain need effective and potent analgesic agents. So it is very important to use analgesic exactly to control pain effectively, cause it can make the patient release their pain, improve their life quality, at the same moment give them a comfort and extra confidence to fight with diseases.According to the mechanism of pharmacological effect, analgesic agents are generally divided into opioid analgesics, such as alkaloid morphine, and non-steroidal anti-inflammatory drugs (NSAID), like aspirin. The opioid analgesics have some side effects such as addiction or respiratory depression and the NSAID has side effects to damage gastrointestinal tract. So it is necessary to search for new effective and nontoxic analgesics in plant-derived secondary metabolites. The antinociceptive substances obtained includealkaloids, terpenoids and flavonoids recently.Caragana microphylla Lam., a plant of Caragana genus (Leguminosae family), is widely distributed in the North and West parts of China. Its roots and seeds have been used to heal swollen and painful throat in folk medicine. And it is also used by the native farmers to prevent sand erosion thus making it stationary.The main compounds in Caragana microphylla Lam. were reported as flavonoids, oligomeric stilbenes, triterpene and alkaloids, but the active components reflecting clinical effectiveness were still unknown. 75% ethanol extraction of the seeds, collected from Huhehaote City of Inner-Mongolia Autonomous Region, People's Republic of China, in July, 2004, was partitioned into five fractions as petroleum spirit, chloroform, acetic ether, n-butanol and water portion. Guided with initial pharmacological activities test on mice stretching model, petroleum and chloroform fractions were showed to have obvious analgesic action on reducing the times of mice writhing reaction caused by acetic acid.
Twenty components were obtained from the chloroform fraction using column chromatography of silica gel, Sephadex LH-20, ODS and HPLC. Sixteen of them were identified on the basis of spectral analysis (UV, IR, EI-MS, FAB-MS, ^-NMR, 13C-NMR, 2D-NMR) and phytochemical properties, and we identified eighteen of them. Among them main components were flavonoids, triterpene and alkaloids. A new compound was elucidated and eleven compounds were isolated from Caragana microphylla Lam. for the first time. And we also identified twenty five compound of the petroleum fraction by GC-MS for the first time. The main compound of it is the linoleic acid (50.64%), oleic acid (17.43%) and palmitic acid (11.67%).The total alkaloids and the five alkaloids were essayed by the mice stretching model. We found that the total alkaloids and some alkaloids showed strong analgesia activity. And according to the traditional use, we also essayed the cytotoxicity activity of all the fractions and compounds in vitro and some compounds showed significant cytotoxicity activity. The results of the essay notified us that the seeds of Caragana microphylla Lam. may become the resource of antinociceptive and anticancer drugs.
目前用于疼痛治疗的药物主要有四类:一类是阿片类镇痛药,具有成瘾性;一类是作用于中枢的非阿片类镇痛药,但无抗炎抗风湿作用,并具有肝毒性;一类是作用于外周的抗炎镇痛药,但长期服用容易引起胃肠损害。一类是复方抗炎镇痛药,但由于联合用药机制的复杂性,该类药物还很少,而且安全性也需要进一步长期观察。
因此目前临床上仍缺乏理想的镇痛药物。近年来国内外对从天然药物中寻找新的镇痛成分研究十分活跃,从天然药物中寻找高效、低毒、无依赖性的镇痛新药将成为主流的发展趋势,已有用于临床的报道,如延胡索乙素、辣椒素等。
柠条籽是豆科锦鸡儿属植物小叶锦鸡儿(Caragana microphylla Lam.)的成熟种子,同时在不同地区也将中间锦鸡儿和树锦鸡儿的成熟种子作为柠条籽入药。其原植物生长于欧亚大陆干旱半干旱地区,主产于我国东北、华北、西北和西南各省区,我国产62种,大多数作为绿化及防风固沙植物,仅有少数应用于药用。柠条籽味苦,性寒。清热利咽,主治咽喉肿痛等症。
国内学者研究表明,锦鸡儿属植物中含有黄酮、二苯乙烯低聚体、三萜、生物碱等化学成分,但反映柠条籽临床功效与药理作用的有效成分有待阐明。目前柠条籽药材尚未被药典收载,且对于其原植物的植物分类学尚存在较大的争议。我们在内蒙古呼和浩特市采集柠条籽,将柠条籽75%乙醇浸膏用水混悬,依次用石油醚、氯仿、乙酸乙酯、正丁醇萃取,分成石油醚、氯仿、乙酸乙酯、正丁醇、水共5个极性部位,并对各部位进行了初步药效学试验,结果表明,柠条籽的总提物、石油醚及氯仿部位(1g
In accordance with the International Association for the Study of Pain, pain has been defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. The pain appears widely in various kinds of diseases in clinic. Thousands of patients with intense and unrelenting pain need effective and potent analgesic agents. So it is very important to use analgesic exactly to control pain effectively, cause it can make the patient release their pain, improve their life quality, at the same moment give them a comfort and extra confidence to fight with diseases.According to the mechanism of pharmacological effect, analgesic agents are generally divided into opioid analgesics, such as alkaloid morphine, and non-steroidal anti-inflammatory drugs (NSAID), like aspirin. The opioid analgesics have some side effects such as addiction or respiratory depression and the NSAID has side effects to damage gastrointestinal tract. So it is necessary to search for new effective and nontoxic analgesics in plant-derived secondary metabolites. The antinociceptive substances obtained includealkaloids, terpenoids and flavonoids recently.Caragana microphylla Lam., a plant of Caragana genus (Leguminosae family), is widely distributed in the North and West parts of China. Its roots and seeds have been used to heal swollen and painful throat in folk medicine. And it is also used by the native farmers to prevent sand erosion thus making it stationary.The main compounds in Caragana microphylla Lam. were reported as flavonoids, oligomeric stilbenes, triterpene and alkaloids, but the active components reflecting clinical effectiveness were still unknown. 75% ethanol extraction of the seeds, collected from Huhehaote City of Inner-Mongolia Autonomous Region, People's Republic of China, in July, 2004, was partitioned into five fractions as petroleum spirit, chloroform, acetic ether, n-butanol and water portion. Guided with initial pharmacological activities test on mice stretching model, petroleum and chloroform fractions were showed to have obvious analgesic action on reducing the times of mice writhing reaction caused by acetic acid.
Twenty components were obtained from the chloroform fraction using column chromatography of silica gel, Sephadex LH-20, ODS and HPLC. Sixteen of them were identified on the basis of spectral analysis (UV, IR, EI-MS, FAB-MS, ^-NMR, 13C-NMR, 2D-NMR) and phytochemical properties, and we identified eighteen of them. Among them main components were flavonoids, triterpene and alkaloids. A new compound was elucidated and eleven compounds were isolated from Caragana microphylla Lam. for the first time. And we also identified twenty five compound of the petroleum fraction by GC-MS for the first time. The main compound of it is the linoleic acid (50.64%), oleic acid (17.43%) and palmitic acid (11.67%).The total alkaloids and the five alkaloids were essayed by the mice stretching model. We found that the total alkaloids and some alkaloids showed strong analgesia activity. And according to the traditional use, we also essayed the cytotoxicity activity of all the fractions and compounds in vitro and some compounds showed significant cytotoxicity activity. The results of the essay notified us that the seeds of Caragana microphylla Lam. may become the resource of antinociceptive and anticancer drugs.
引文
Bhakuni DS, Chaturvedi R., 1983. The alkaloids of Corydalis meifolia. J Nat Prod. 46, (4):466-70.
Cao WH, Zhang XY., 1991. Anatomy of secondary xylem of six psammophytes of Caragana Fabr.. Acta Botanica Sinica. 33 (3): 181—187.
Cao CY, Jiang DM, Alamsa, Luo, Y., Kou, Z., 2000. Ecological process of vegetation restoration in Caragana microphylla sand-fixing area. Chinese Journal of Applied Ecology 11,349-354.
Chao ZY., 1988. Fat content and fat acid characteristic of seeds of Caragana Fabr.Shaanxi Forest Science and Technology. (3): 1～3.
Chen Bo, 2002. Chemical research of Caragana intermedia Kuang et H. C. Fu (Ⅰ) [master's thesis]. School of pharmacy, Fudan University.
Chen Y, Chiu MH, Gu K, Li ZR., 2003. Cucurbitacin and triterpenoid glycosides from Hemsleya giganthy. Chinese Chemical Letters. 14(5), 475-478.
Christiane Halbsguth, Oliver Meibner, Hanns Haberlein., 2003. Positive cooperation of protoberberine type 2 alkaloids from Corydalis cava on the GABAA binding site. Planta Med. 69:305-309.
Cold and Arid Regions Environmental and Engineering Research Institute, CAS., 1973. Chinese Desert Medicinal Plants. Lanzhou: Gansu people's press.
Collier H.O.J., Dinneen L.C., Johnson C.A., et al., 1968. The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br J Pharmacol. 32, 295-310.
Cui YL, Mu Q, Hu CQ., 2003. Studies on the phenylpropanoids from Caragana rosea. Natural Product Research and Development, 15(4):277.
Delectis florae reiublicae popularis snicae agendae academiae sinicae edita., 1993. Flora reipublicae popularis sinicae. [Tomus 42(1)]. Bei jing: Science Press.
Department of chronic tracheitis, Baotou Medical School, 1977. Phytochemistry and Pharmacological Research of Caragana microphylla. Baotou Medicine, (1): 52—52.
Department of Microorganism, Baotou Medical School, 1977. Bacteriostasis activity of Caragara microphylla. Baotou Medicine, (1): 63—63.
Department of Pharmacology, Baotou Medical school, 1977. Antiinflammatory and GC activities of Caragana microphylla. Baotou Medicine, (1): 79—79.
Dionne RA, Khan AA, Gordon SM., 2001. Analgesia and COX-2 inhibition. Clin Exp Rheumatol. 19(6 Suppl 25), 63-70.
Djerassi C, Liu, LH, Farkas E. et al., 1955. Terpenoids. Ⅺ. Investigation of nine cactus species. Isolation of two new triterpenes, stellatogenin and Machaeric acid [J]. J Am Chem Soc, 77: 1200-3.
Du XW, Guo XL, Guo CL, et al. The clinical research of anti-rheumatoid arthritis from Cara gana., 1998. Journal of Medicine & Pharmacy of Chinese Minorities, 4(2): 11.
Duarte I.D.G., Nakamura M., Ferreira S.H., et al., 1988. Participation of the sympathetic system in acetic acid-induced writhing in mice. Braz J Med Biol Res. 21, 341-343.
Feng SL, He L, Wang M, et al., 1994. Studies on the Chemical Constituents of Flower of David Lily. China J Chinese Mater Med. 19, (9): 611-612.
Gang Chen, Hongfeng Luo, Jiannong Ye, Changqi Hu., 2001. Identification and Determination of Oligomeric Stilbenes in the Roots of Caragana Species by Capillary Electrophoresis. Planta Med. 67: 665-668.
Gaydou Emile M., Bianchini Jean Pierre., 1978. Studies on fiavone compounds Ⅰ. Syntheses and [spectral] properties (UV, carbon-13 NMR) of some flavones. Bull Soc Chim Fr. (1-2, Pt. 2): 43-7.
Gendzalason, 1987. The Dictionary of Traditional Mongolian Medicine. Inner Mongolia: Inner Mongolian people's press.
Hu Y., 1992. The effections of Caragana microphylla's apozema on humoral immunity. Journal of Baotao Medicine. 16 (4): 9—9.
Hunskaar S., Hole K.., 1987. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain. 30, 103-114.
Iizuka, N., Hirose, K., Noma, T., et al, 1999. The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma. British Journal of Cancer. 81,469-475.
Ikuta A., Itokawa H., 1988. Alkaloids of tissue cultures of Nandina domestica. Phytochemistry. 27(7), 2143-5.
Inner Mongolian People's press, 1972. The herbal medicines of Inner Mongolia. The Board of Health of Inner Mongolian Revolutionary Committee, China 408-419
Jia Li, Qu Shi-zeng, 2001. The study progress on the genus Caragana Fabr..Bulletin of Botanical Research. 21(4): 515-518.
Jia SS, Dong Y, Zheng F. et al., 1991. The isolation and identification of isoflavone glycoside from the root of Caragana intermedia. Chinese Traditional and Herbal Drugs. 22(10): 441.
Jia SS, Zhou GK., 1988. The isolation and identification of isoflavone from the root of Caragana intermedia. Letter of TCM. 13(12): 34.
Jin GZ, Li JD, Ahn BZ., 1992. Isoflavones from the root of Caragana microphylla Lam.. Yakhak Hoechi. 36(5):481.
Jin JJ, Fang WL, Jin ZN, et al., 1993. The anti-inflammatory activity of Caragana microfylla Lam.. China Journal of Chinese Materia Medica, 18(5): 306.
Jin, Z. N., Jin, J. J., Jin, G. Z., 1994. The pharmacology research of Caragana microphylla Lam.. Journal of Medical Science Yanbian University 17(4), 267.
Joao B. Calixto, Alessandra Beirith, Juliano Ferreira, et al., 2000. Naturally Occurring Antinociceptive Substances from Plants. Phytother Res. 14, 401-418.
Kinuko, I., Yumi, N., Momoyo, I., Masataka, M., Kim, H. S., Yusuke, W., Takao, Y., Turuo, T., Lee, D. U., 1999. Structure-activity relationships of quaternary protoberberine alkaloids having an antimalarial activity. European Journal of Medicinal Chemistry 34, 1077-1083.
Koster, R., Anderson, M., Beer, E. J., 1959. Acetic acid for analgesic screening. Fed Proc. 18, 412-417.
Kulanthaivel P, Janzen WP, Ballas LM, et al., 1995. Naturally occurring protein kinase C inhibitions Ⅱ isolation of oligomeric stilbenes from Caragana sinica. Planta Med. 61(1):41.
Li MZ, Zhang HY, Wu ZJ, et al., 1994. Effect of Chinese peashrub (Caragana sinica) extract on hemorheology in rabbits. Chinese Traditional and Herbal Drugs. 25(12): 637
Lin WH, Fu HZ, Zhang LH., 1998. Two new triterpenoids from the roots of Caragana intermedia K. Journal of Chinese Pharmaceutical Sciences. 7(1): 1.
Lin Y, Zhang C, Hua WY., 2002. Development of study on structure-activity relationships of protoberberine alkaloids. Progress in pharmaceutical sciences. 26 (2): 76-80.
Lin HL, Liu TY, Wu CW, Chi CW, 1999. Berberine modulates expression of mdrl gene product and the responses of digestive track cancer cells to Paclitaxel. British Journal of Cancer 81,416-422.
Liu HM, Ke Y, Liu ZZ., 2003. Structures of 4, 6, 1, 6-Tetrachloro-4, 6, 1', 6'-Tetradeoxygalactosucrose and its Derivatives Determined by ~1H and ~(13)C NMR. Chinese J Magn Reson. 20, (4): 357-361.
Liu HX, Lin WH, Yang JS., 2004. Research of Chemical components and bioactivities of Caragana Fabr. Chin Pharm J. 39(5), 327-330.
Loro, J.F., del Rio, I., Perez-Santana, L., 1999. Preliminary studies of analgesic and anti-inflammatory properties of Opuntia dillenii aqueous extract. J Ethnopharmacol. 67, 213-218.
Luo HF, Zhang LP, Hu CQ., 2000. The research of Oligomeric stilbenes from the root of Caragana sinica. Chinese Traditional and Herbal Drugs. 31(9): 654.
Luo HF, Zhang LP, Hu CQ., 2001. Five novel oligostilbenes from the root of Caragana sinica. Tetrahedron. 57: 4849.
Ma CC, Gao YB, Guo HY, et al., 2003. Interspecific transition among Caragana microphylla, C. davazamcii and C. korshinskii along geographic gradient. Ⅱ. Characteristics of photosynthesis and water metabolism. Acta Botanica Sinica. 45(10):1228-1237.
Ma CC, Gao YB, Liu HF et al., 2003. Interspecific transition among Caragana microphylla, C. davazamcii and C. korshinskii along geographic gradient. Ⅰ. Ecological and RAPD evidence. Acta Botanica Siniea. 45(10): 1281-1227.
Ma DY, Luo HF, Hu CQ., 2004. Three stilbene tetramers from the roots of Caragana sinica. Chinese Journal of Chemistry. 22:207
Mamuti Kerban, 2005. Assay on Total Alkaloid in Xinjiang Cydonia Oblonga Mill. Food Science, (26)2:186-189
Ma YQ, et al., 1977. Flora Nei Mongol.(Version Ⅰ), Nei menggu: Inner Mongolian People's Press.
Ma YQ, et al., 1989.Flora Nei Mongol.(Version Ⅱ), Nei menggu: Inner Mongolian People's Press.
Meng QX , Niu Y, Niu XW., 2005. Determination of Total Flavonoids Content of Several Species in Caragana Fabr. Acta AgriculturaeBareali-Sinica. 20(3): 43-45.
Merrgen, Ma yuquan., 1991. Overlaps in diagnostic characteristics of three afinity species of Caragana Fabr. and responds of the overlaps on pollen morphology. Acta Scientiarum Naturalium Universitatis Nei Mongol. 22(4): 539-544.
Niu XW., 1999. The distribution and description of Caragana Fabr. in China. Acta Bot. Boreal.-Occident. Sin.. 19(5): 107-133
Peng Shulin, Chen weixin, Sakagami yoji, Marumo Shingo., 1992. Studies on medicinal isoquinoline alkaloids Ⅳ. Alkaloids of Corudalis omeienensis. Natural product research and development. 4(2): 07-14
Piao HS, Jin YF, Zhang SY., 2005. Experimental study on anti-tumor effects of the n-butanol extraction of Caragana Microphylla Lam. in mice. Journal of Medical Science Yanbian University. 28(2): 107-109.
Piao, H.S., Jin, G.Z., Zhang, S.Y., 2004. Inhibitory effects of Caragana microphylla Lam. on sarcoma_(180) in mice. Journal of Medical Science Yanbian University, 27(1),16.
Qiu Jun, Sun Jingtia., 2003. A study on pollen morphology of Caragana Fabr. and it's taxonomic significance. Journal of Sandong Normal University(Natural Science). 18(1): 85-87.
Qu SB, Zhang XX., 1989. The clinical researches of anti-hypertension effects from Caragana. The Practical Journal of Integrating Chinese with Modern Medicine. 2 (2:10).
Sanders, M.M., Liu, A.A., Li, T.K., et al., 1998. Selective cytotoxicity of topoisomerase-directed protoberberines against glioblastoma cells. Biochemical Pharmacology, 56, 1157-1166.
Shanghai Scientific&Technical Press, 1985. The Dictionary of Traditional Medicine. Jiangsu New Medical College, China, 92-393.
Shanghai Scientific&Technical Press, 1997. Chinese Herbals. The editor board of Chinese Herbals, China, (volum 4): 388-396.
Sheng Z, Tian CY, Wang YX, et al., 1999. Effects of Miyabenol C on Protein Kinase C in Two Lung Carcinoma Cell Lines. J Shanghai Med Univ. 26(6): 35.
Shi J, Chen B, Sun ZH, Hu CQ., 2003. Studies on flavonoid constituents of Caragana intermedia. Acta Pharmaceutica Sinica. 38(8): 599-602.
Shi jiao., 2003. Chemical research of Caragana intermedia Kuang et H. C. Fu (Ⅲ) [master's thesis]. School of pharmacy, Fudan University.
Slavik, J., Slavikova, L., 1979. Alkaloids of the Papaveraceae. LⅩⅦ. Alkaloids from Corydalis cava (L.) Schw. et Koerte. Collection of Czechoslovak Chemical Communications, 44(7), 2261-2274.
Slowing K, Sollhuber M, Carretero E, Villar A., 1994. Flavonoid glycosides from Eugenia jambos. Phytochemistry. 37(1): 255-8.
Stermitz, F.R., Lorenz, P., Tawara, J.N., Zenewicz, L.A., Lewis, K., 2000. Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5'-methoxyhydnocarpin, a multidrug pump inhibitor. Proceedings of National Academy of Science USA, 97, 1433-1437.
Su, Y.Z., Zhao, H.L., 2003. Soil properties and plant species in an age sequence of Caragana microphylla plantations in the Horqin Sandy Land, north China. Ecological Engineering, (20), 223-235.
Sun ZH, Chen B, Hu CQ, et al., 2004. Four new eudesmanes from Caragana intermedia and their biological activities. Journal of Natural Products. 67(12):1975-9.
Sun ZH, 2004. Study on the sesquiterpenes from Caragana intermedia Kuang et H. C. Fu and their activities[doctorial thesis]. School of pharmacy, Fudan University.
Susumu K, Michio T, Kazutoshi M, et al., 1996. Oligomeric stilbenes from Caragana chamlagu Lamark root. Chem Pharm Bull. 44 (3): 565.
Tong, S.Q., Yan, J.Z., Lou, J.Z., 2005. Preparative Isolation and Purification of Alkaloids from Corydalis yanhusuo W. T. Wang by High Speed Counter-Current Chromatography. Journal of liquid chromatography & related technologies, 28(18), 2979-2989.
Vogel H G, Vogel W H., 2001. Guide of Pharmacological Experiment-Discovery of New Drug and the Pharmacological Estimate. Bei jing: Science Press.
Wang Hengshan, Yang Hairong., 1997. The alkaloids of Corydalis dasypterm Maxim. Natural product research and development. 9(1): 37-39
Woo ER, Kin HJ, Kwak JH, et al., 1997. Inhibition of gp-120-CD4 interaction by various plant extracts. Phytomedicine. 4(1):53.
Wu LJ, et al., 2004. Tian Ran Yao Wu Hua Xue. Beijing: People's Medical Publishing House.
Xu JJ, Hai LQ, Wang XQ., 2005. Chemical constituents of Hedysarum austrosibiricum b. Fedtsch. W C J·P S. 20, (3): 214-215.
Yang GX, Hu CQ., 2003. A new stilbene tetramer from Caragana rosea. Chinese Chemical letters. 14(10): 1048.
Yang GX, Hu CQ., 2003. A new stilbenolignan from Caragana rosea Turcz.. Chinese Journal of Organic Chemistry. 23(8):873
Yet Ran Chen, Kuo Ching Wen, Guor Rong Her., 2000. Analysis of coptisine, berberine and palmatine in adulterated Chinese medicine by capillary electrophoresis-electrospray ion trap mass spectrometry. Journal of Chromatography A, 866:273-280.
Yin YY, Wang YL, Jiang Q, et al., 2000. The analgesic effect of Angelic Enrich Blood Decoction. Acta Univ Med Anhui. 35(5): 355—356.
Yu DQ, Yang JS, et al, 1999. Analytical Chemistry Handbook (version Ⅱ). Beijing: Chemical Industry Press.
Zhang HY, Jin SZ, Dai YW, et al., 1998. Effect of Chinese peashrub (Caragana sinica) extract on platelet adhering function and experimental thrombosis in rabbits. Chinese Traditional and Herbal Drugs, 29(6): 393.
Zhang Su., 2004. Chemical research of Caragana intermedia Kuang et H. C. Fu (Ⅳ) [master's thesis]. School of pharmacy, Fudan University.
Zhang WP., 1992. Anti-flammatory activity of Caragana aboresense. Journal of Batou Medical College. 9 (2): 6—6.
Zhang XF., 1992. Studies on the common Fixators of Genus Caragana Fabr. Journal of Desert Research. 12 (2): 39—46.
Zhang ZW, Yang SX., 1983. Caragana Fabr. of Sanxi province. Acta Bot. Boreal.-Occident. Sin.. (3): 21—31.
Zhao YZ., 1990. The study of the Caragana davazamcii (Laeguminoceae). Acta Scientiarum Naturalium Universitatis Nei Mongol. 21 (4): 560—563.
Zhao YZ., 1993. Taxonomical Study of the Genus Caragana from China. Acta Scientiarum Naturalium Universitatis Nei Mongol. 24 (6): 631—653.
Cao WH, Zhang XY., 1991. Anatomy of secondary xylem of six psammophytes of Caragana Fabr.. Acta Botanica Sinica. 33 (3): 181—187.
Cao CY, Jiang DM, Alamsa, Luo, Y., Kou, Z., 2000. Ecological process of vegetation restoration in Caragana microphylla sand-fixing area. Chinese Journal of Applied Ecology 11,349-354.
Chao ZY., 1988. Fat content and fat acid characteristic of seeds of Caragana Fabr.Shaanxi Forest Science and Technology. (3): 1～3.
Chen Bo, 2002. Chemical research of Caragana intermedia Kuang et H. C. Fu (Ⅰ) [master's thesis]. School of pharmacy, Fudan University.
Chen Y, Chiu MH, Gu K, Li ZR., 2003. Cucurbitacin and triterpenoid glycosides from Hemsleya giganthy. Chinese Chemical Letters. 14(5), 475-478.
Christiane Halbsguth, Oliver Meibner, Hanns Haberlein., 2003. Positive cooperation of protoberberine type 2 alkaloids from Corydalis cava on the GABAA binding site. Planta Med. 69:305-309.
Cold and Arid Regions Environmental and Engineering Research Institute, CAS., 1973. Chinese Desert Medicinal Plants. Lanzhou: Gansu people's press.
Collier H.O.J., Dinneen L.C., Johnson C.A., et al., 1968. The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br J Pharmacol. 32, 295-310.
Cui YL, Mu Q, Hu CQ., 2003. Studies on the phenylpropanoids from Caragana rosea. Natural Product Research and Development, 15(4):277.
Delectis florae reiublicae popularis snicae agendae academiae sinicae edita., 1993. Flora reipublicae popularis sinicae. [Tomus 42(1)]. Bei jing: Science Press.
Department of chronic tracheitis, Baotou Medical School, 1977. Phytochemistry and Pharmacological Research of Caragana microphylla. Baotou Medicine, (1): 52—52.
Department of Microorganism, Baotou Medical School, 1977. Bacteriostasis activity of Caragara microphylla. Baotou Medicine, (1): 63—63.
Department of Pharmacology, Baotou Medical school, 1977. Antiinflammatory and GC activities of Caragana microphylla. Baotou Medicine, (1): 79—79.
Dionne RA, Khan AA, Gordon SM., 2001. Analgesia and COX-2 inhibition. Clin Exp Rheumatol. 19(6 Suppl 25), 63-70.
Djerassi C, Liu, LH, Farkas E. et al., 1955. Terpenoids. Ⅺ. Investigation of nine cactus species. Isolation of two new triterpenes, stellatogenin and Machaeric acid [J]. J Am Chem Soc, 77: 1200-3.
Du XW, Guo XL, Guo CL, et al. The clinical research of anti-rheumatoid arthritis from Cara gana., 1998. Journal of Medicine & Pharmacy of Chinese Minorities, 4(2): 11.
Duarte I.D.G., Nakamura M., Ferreira S.H., et al., 1988. Participation of the sympathetic system in acetic acid-induced writhing in mice. Braz J Med Biol Res. 21, 341-343.
Feng SL, He L, Wang M, et al., 1994. Studies on the Chemical Constituents of Flower of David Lily. China J Chinese Mater Med. 19, (9): 611-612.
Gang Chen, Hongfeng Luo, Jiannong Ye, Changqi Hu., 2001. Identification and Determination of Oligomeric Stilbenes in the Roots of Caragana Species by Capillary Electrophoresis. Planta Med. 67: 665-668.
Gaydou Emile M., Bianchini Jean Pierre., 1978. Studies on fiavone compounds Ⅰ. Syntheses and [spectral] properties (UV, carbon-13 NMR) of some flavones. Bull Soc Chim Fr. (1-2, Pt. 2): 43-7.
Gendzalason, 1987. The Dictionary of Traditional Mongolian Medicine. Inner Mongolia: Inner Mongolian people's press.
Hu Y., 1992. The effections of Caragana microphylla's apozema on humoral immunity. Journal of Baotao Medicine. 16 (4): 9—9.
Hunskaar S., Hole K.., 1987. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain. 30, 103-114.
Iizuka, N., Hirose, K., Noma, T., et al, 1999. The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma. British Journal of Cancer. 81,469-475.
Ikuta A., Itokawa H., 1988. Alkaloids of tissue cultures of Nandina domestica. Phytochemistry. 27(7), 2143-5.
Inner Mongolian People's press, 1972. The herbal medicines of Inner Mongolia. The Board of Health of Inner Mongolian Revolutionary Committee, China 408-419
Jia Li, Qu Shi-zeng, 2001. The study progress on the genus Caragana Fabr..Bulletin of Botanical Research. 21(4): 515-518.
Jia SS, Dong Y, Zheng F. et al., 1991. The isolation and identification of isoflavone glycoside from the root of Caragana intermedia. Chinese Traditional and Herbal Drugs. 22(10): 441.
Jia SS, Zhou GK., 1988. The isolation and identification of isoflavone from the root of Caragana intermedia. Letter of TCM. 13(12): 34.
Jin GZ, Li JD, Ahn BZ., 1992. Isoflavones from the root of Caragana microphylla Lam.. Yakhak Hoechi. 36(5):481.
Jin JJ, Fang WL, Jin ZN, et al., 1993. The anti-inflammatory activity of Caragana microfylla Lam.. China Journal of Chinese Materia Medica, 18(5): 306.
Jin, Z. N., Jin, J. J., Jin, G. Z., 1994. The pharmacology research of Caragana microphylla Lam.. Journal of Medical Science Yanbian University 17(4), 267.
Joao B. Calixto, Alessandra Beirith, Juliano Ferreira, et al., 2000. Naturally Occurring Antinociceptive Substances from Plants. Phytother Res. 14, 401-418.
Kinuko, I., Yumi, N., Momoyo, I., Masataka, M., Kim, H. S., Yusuke, W., Takao, Y., Turuo, T., Lee, D. U., 1999. Structure-activity relationships of quaternary protoberberine alkaloids having an antimalarial activity. European Journal of Medicinal Chemistry 34, 1077-1083.
Koster, R., Anderson, M., Beer, E. J., 1959. Acetic acid for analgesic screening. Fed Proc. 18, 412-417.
Kulanthaivel P, Janzen WP, Ballas LM, et al., 1995. Naturally occurring protein kinase C inhibitions Ⅱ isolation of oligomeric stilbenes from Caragana sinica. Planta Med. 61(1):41.
Li MZ, Zhang HY, Wu ZJ, et al., 1994. Effect of Chinese peashrub (Caragana sinica) extract on hemorheology in rabbits. Chinese Traditional and Herbal Drugs. 25(12): 637
Lin WH, Fu HZ, Zhang LH., 1998. Two new triterpenoids from the roots of Caragana intermedia K. Journal of Chinese Pharmaceutical Sciences. 7(1): 1.
Lin Y, Zhang C, Hua WY., 2002. Development of study on structure-activity relationships of protoberberine alkaloids. Progress in pharmaceutical sciences. 26 (2): 76-80.
Lin HL, Liu TY, Wu CW, Chi CW, 1999. Berberine modulates expression of mdrl gene product and the responses of digestive track cancer cells to Paclitaxel. British Journal of Cancer 81,416-422.
Liu HM, Ke Y, Liu ZZ., 2003. Structures of 4, 6, 1, 6-Tetrachloro-4, 6, 1', 6'-Tetradeoxygalactosucrose and its Derivatives Determined by ~1H and ~(13)C NMR. Chinese J Magn Reson. 20, (4): 357-361.
Liu HX, Lin WH, Yang JS., 2004. Research of Chemical components and bioactivities of Caragana Fabr. Chin Pharm J. 39(5), 327-330.
Loro, J.F., del Rio, I., Perez-Santana, L., 1999. Preliminary studies of analgesic and anti-inflammatory properties of Opuntia dillenii aqueous extract. J Ethnopharmacol. 67, 213-218.
Luo HF, Zhang LP, Hu CQ., 2000. The research of Oligomeric stilbenes from the root of Caragana sinica. Chinese Traditional and Herbal Drugs. 31(9): 654.
Luo HF, Zhang LP, Hu CQ., 2001. Five novel oligostilbenes from the root of Caragana sinica. Tetrahedron. 57: 4849.
Ma CC, Gao YB, Guo HY, et al., 2003. Interspecific transition among Caragana microphylla, C. davazamcii and C. korshinskii along geographic gradient. Ⅱ. Characteristics of photosynthesis and water metabolism. Acta Botanica Sinica. 45(10):1228-1237.
Ma CC, Gao YB, Liu HF et al., 2003. Interspecific transition among Caragana microphylla, C. davazamcii and C. korshinskii along geographic gradient. Ⅰ. Ecological and RAPD evidence. Acta Botanica Siniea. 45(10): 1281-1227.
Ma DY, Luo HF, Hu CQ., 2004. Three stilbene tetramers from the roots of Caragana sinica. Chinese Journal of Chemistry. 22:207
Mamuti Kerban, 2005. Assay on Total Alkaloid in Xinjiang Cydonia Oblonga Mill. Food Science, (26)2:186-189
Ma YQ, et al., 1977. Flora Nei Mongol.(Version Ⅰ), Nei menggu: Inner Mongolian People's Press.
Ma YQ, et al., 1989.Flora Nei Mongol.(Version Ⅱ), Nei menggu: Inner Mongolian People's Press.
Meng QX , Niu Y, Niu XW., 2005. Determination of Total Flavonoids Content of Several Species in Caragana Fabr. Acta AgriculturaeBareali-Sinica. 20(3): 43-45.
Merrgen, Ma yuquan., 1991. Overlaps in diagnostic characteristics of three afinity species of Caragana Fabr. and responds of the overlaps on pollen morphology. Acta Scientiarum Naturalium Universitatis Nei Mongol. 22(4): 539-544.
Niu XW., 1999. The distribution and description of Caragana Fabr. in China. Acta Bot. Boreal.-Occident. Sin.. 19(5): 107-133
Peng Shulin, Chen weixin, Sakagami yoji, Marumo Shingo., 1992. Studies on medicinal isoquinoline alkaloids Ⅳ. Alkaloids of Corudalis omeienensis. Natural product research and development. 4(2): 07-14
Piao HS, Jin YF, Zhang SY., 2005. Experimental study on anti-tumor effects of the n-butanol extraction of Caragana Microphylla Lam. in mice. Journal of Medical Science Yanbian University. 28(2): 107-109.
Piao, H.S., Jin, G.Z., Zhang, S.Y., 2004. Inhibitory effects of Caragana microphylla Lam. on sarcoma_(180) in mice. Journal of Medical Science Yanbian University, 27(1),16.
Qiu Jun, Sun Jingtia., 2003. A study on pollen morphology of Caragana Fabr. and it's taxonomic significance. Journal of Sandong Normal University(Natural Science). 18(1): 85-87.
Qu SB, Zhang XX., 1989. The clinical researches of anti-hypertension effects from Caragana. The Practical Journal of Integrating Chinese with Modern Medicine. 2 (2:10).
Sanders, M.M., Liu, A.A., Li, T.K., et al., 1998. Selective cytotoxicity of topoisomerase-directed protoberberines against glioblastoma cells. Biochemical Pharmacology, 56, 1157-1166.
Shanghai Scientific&Technical Press, 1985. The Dictionary of Traditional Medicine. Jiangsu New Medical College, China, 92-393.
Shanghai Scientific&Technical Press, 1997. Chinese Herbals. The editor board of Chinese Herbals, China, (volum 4): 388-396.
Sheng Z, Tian CY, Wang YX, et al., 1999. Effects of Miyabenol C on Protein Kinase C in Two Lung Carcinoma Cell Lines. J Shanghai Med Univ. 26(6): 35.
Shi J, Chen B, Sun ZH, Hu CQ., 2003. Studies on flavonoid constituents of Caragana intermedia. Acta Pharmaceutica Sinica. 38(8): 599-602.
Shi jiao., 2003. Chemical research of Caragana intermedia Kuang et H. C. Fu (Ⅲ) [master's thesis]. School of pharmacy, Fudan University.
Slavik, J., Slavikova, L., 1979. Alkaloids of the Papaveraceae. LⅩⅦ. Alkaloids from Corydalis cava (L.) Schw. et Koerte. Collection of Czechoslovak Chemical Communications, 44(7), 2261-2274.
Slowing K, Sollhuber M, Carretero E, Villar A., 1994. Flavonoid glycosides from Eugenia jambos. Phytochemistry. 37(1): 255-8.
Stermitz, F.R., Lorenz, P., Tawara, J.N., Zenewicz, L.A., Lewis, K., 2000. Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5'-methoxyhydnocarpin, a multidrug pump inhibitor. Proceedings of National Academy of Science USA, 97, 1433-1437.
Su, Y.Z., Zhao, H.L., 2003. Soil properties and plant species in an age sequence of Caragana microphylla plantations in the Horqin Sandy Land, north China. Ecological Engineering, (20), 223-235.
Sun ZH, Chen B, Hu CQ, et al., 2004. Four new eudesmanes from Caragana intermedia and their biological activities. Journal of Natural Products. 67(12):1975-9.
Sun ZH, 2004. Study on the sesquiterpenes from Caragana intermedia Kuang et H. C. Fu and their activities[doctorial thesis]. School of pharmacy, Fudan University.
Susumu K, Michio T, Kazutoshi M, et al., 1996. Oligomeric stilbenes from Caragana chamlagu Lamark root. Chem Pharm Bull. 44 (3): 565.
Tong, S.Q., Yan, J.Z., Lou, J.Z., 2005. Preparative Isolation and Purification of Alkaloids from Corydalis yanhusuo W. T. Wang by High Speed Counter-Current Chromatography. Journal of liquid chromatography & related technologies, 28(18), 2979-2989.
Vogel H G, Vogel W H., 2001. Guide of Pharmacological Experiment-Discovery of New Drug and the Pharmacological Estimate. Bei jing: Science Press.
Wang Hengshan, Yang Hairong., 1997. The alkaloids of Corydalis dasypterm Maxim. Natural product research and development. 9(1): 37-39
Woo ER, Kin HJ, Kwak JH, et al., 1997. Inhibition of gp-120-CD4 interaction by various plant extracts. Phytomedicine. 4(1):53.
Wu LJ, et al., 2004. Tian Ran Yao Wu Hua Xue. Beijing: People's Medical Publishing House.
Xu JJ, Hai LQ, Wang XQ., 2005. Chemical constituents of Hedysarum austrosibiricum b. Fedtsch. W C J·P S. 20, (3): 214-215.
Yang GX, Hu CQ., 2003. A new stilbene tetramer from Caragana rosea. Chinese Chemical letters. 14(10): 1048.
Yang GX, Hu CQ., 2003. A new stilbenolignan from Caragana rosea Turcz.. Chinese Journal of Organic Chemistry. 23(8):873
Yet Ran Chen, Kuo Ching Wen, Guor Rong Her., 2000. Analysis of coptisine, berberine and palmatine in adulterated Chinese medicine by capillary electrophoresis-electrospray ion trap mass spectrometry. Journal of Chromatography A, 866:273-280.
Yin YY, Wang YL, Jiang Q, et al., 2000. The analgesic effect of Angelic Enrich Blood Decoction. Acta Univ Med Anhui. 35(5): 355—356.
Yu DQ, Yang JS, et al, 1999. Analytical Chemistry Handbook (version Ⅱ). Beijing: Chemical Industry Press.
Zhang HY, Jin SZ, Dai YW, et al., 1998. Effect of Chinese peashrub (Caragana sinica) extract on platelet adhering function and experimental thrombosis in rabbits. Chinese Traditional and Herbal Drugs, 29(6): 393.
Zhang Su., 2004. Chemical research of Caragana intermedia Kuang et H. C. Fu (Ⅳ) [master's thesis]. School of pharmacy, Fudan University.
Zhang WP., 1992. Anti-flammatory activity of Caragana aboresense. Journal of Batou Medical College. 9 (2): 6—6.
Zhang XF., 1992. Studies on the common Fixators of Genus Caragana Fabr. Journal of Desert Research. 12 (2): 39—46.
Zhang ZW, Yang SX., 1983. Caragana Fabr. of Sanxi province. Acta Bot. Boreal.-Occident. Sin.. (3): 21—31.
Zhao YZ., 1990. The study of the Caragana davazamcii (Laeguminoceae). Acta Scientiarum Naturalium Universitatis Nei Mongol. 21 (4): 560—563.
Zhao YZ., 1993. Taxonomical Study of the Genus Caragana from China. Acta Scientiarum Naturalium Universitatis Nei Mongol. 24 (6): 631—653.