Advertisement

An Evidence-based Perspective of Angelica Sinensis (Chinese Angelica) for Cancer Patients

  • Po-Cheng Lin
  • Tzyy-Wen Chiou
  • Horng-Jyh Harn
Chapter
Part of the Evidence-based Anticancer Complementary and Alternative Medicine book series (ACAM)

Abstract

The main compounds in Angelica sinensis (Chinese angelica) acetone extract AS-C are ferulic acid, ligustilide, brefeldin A, butylidenephthalide, as well as polysaccharides. Polysaccharide have been determined their effects on various human cancer cells. Subsequently, the active component of AS-C, butylidenephthalide (BP), has been investigated for its antitumor effects on glioblastoma multiforme (GBM) brain tumors and colon cancer. In vitro, GBM cells were treated with BP, and the effects on proliferation, cell cycle, and apoptosis were determined. In vivo, the human GBM tumor, DBTRG-05MG and RG2, the rat GBM tumor, were injected subcutaneously or intracerebrally with BP. BP increased the expression of cyclin kinase inhibitor, including p21 and p27, to decrease the phosphorylation of the Rb proteins, and down-regulated the cell cycle regulators, resulting in cell arrest and apoptosis at the G0/G1 phase. We also examined BP-induced changes in gene expression by microarray screening using human GBM brain tumor cells. Among these genes, Nur77 is particularly interesting because it plays an important role in the apoptotic processes in various tumor cell lines. BP was able to increase Nur77 mRNA and protein expression in a time-dependent manner. After the GBM 8401 cells were treated with BP, Nur77 translocated from the nucleus to the cytoplasm while the cytochrome c was released from the mitochondria, and caspase-3 became activated. Since BP has difficulty passing through the blood-brain barrier, we developed a local release system that incorporates BP into a biodegradable polyanhydride material, p(CPP-SA) (BP/Wafer), and investigated its antitumor effects. We used two xenograft animal models, F344 rats (for rat GBM) and nude mice (for human GBM), which were injected with RG2 and DBTRG-05MG cells, respectively, for tumor formation and subsequently treated subcutaneously with BP Wafers. In addition, to study the effect of the interstitial administration of BP against cranial brain tumors, BP/Wafers were surgically placed in FGF-SV40 transgenic mice. Our BP/Wafer significantly reduced tumor size and prolonged survival in a dose-dependent manner.

Keywords

BCNU Wafer Brain Cancer Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We would like to thank Shinn-Zong Lin (Center for Neuropsychiatry, China Medical University and Hospital, Taichung; Department of Neurosurgery, China Medical University Beigan Hospital, Yunlin, Taiwan), Po-Yen Liu (Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan), Yeu-Chern Harn (Graduate Institute of Networking and Multimedia, National Taiwan University, Taipei, Taiwan), Li-Fu Chang (Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan), and Ivy I-Wei Lin (School of Medicine, China Medical University, Taichung, Taiwan) for their contributions.

References

  1. Bardon, S., Foussard, V., Fournel, S., et al. (2002). Monoterpenes inhibit proliferation of human colon cancer cells by modulating cell cycle-related protein expression. Cancer Letters, 181, 187–194.PubMedCrossRefGoogle Scholar
  2. Belanich, M., Pastor, M., Randall, T., et al. (1996). Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. Cancer Research, 56, 783–788.PubMedGoogle Scholar
  3. Bello, L., Carrabba, G., Giussani, C., et al. (2001). Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo. Cancer Research, 61, 7501–7506.PubMedGoogle Scholar
  4. Blacklock, J. B., Wright, D. C., Dedrick, R. L., et al. (1986). Drug streaming during intra-arterial chemotherapy. Journal of Neurosurgery, 64, 284–291.PubMedCrossRefGoogle Scholar
  5. Blagoev, K. B. (2009). Cell proliferation in the presence of telomerase. PLoS One, 4, e4622.CrossRefGoogle Scholar
  6. Bonham, M., Arnold, H., Montgomery, B., et al. (2002). Molecular effects of the herbal compound PC-SPES: Identification of activity pathways in prostate carcinoma. Cancer Research, 62, 3920–3924.PubMedGoogle Scholar
  7. Bowers, G., He, J., Schulz, K., et al. (2003). Efficacy of adenoviral p53 delivery with SCH58500 in the intracranial 9 l and RG2 models. Frontiers in Bioscience: A Journal and Virtual Library, 8, a54–a61.CrossRefGoogle Scholar
  8. Cao, W., Li, X. Q., Liu, L., et al. (2006). Structural analysis of water-soluble glucans from the root of Angelica sinensis (Oliv.) Diels. Carbohydrate Research, 341, 1870–1877.PubMedCrossRefGoogle Scholar
  9. Cao, W., Li, X. Q., Wang, X., et al. (2010). Characterizations and anti-tumor activities of three acidic polysaccharides from Angelica sinensis (Oliv.) Diels. International Journal of Biological Macromolecules, 46, 115–122.PubMedCrossRefGoogle Scholar
  10. Chang, B. D., Broude, E. V., Dokmanovic, M., et al. (1999). A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents. Cancer Research, 59, 3761–3767.PubMedGoogle Scholar
  11. Chen, Q. C., Lee, J., Jin, W., et al. (2007). Cytotoxic constituents from angelicae sinensis radix. Archives of Pharmacal Research, 30, 565–569.PubMedCrossRefGoogle Scholar
  12. Chen, Y. L., Jian, M. H., Lin, C. C., et al. (2008). The induction of orphan nuclear receptor Nur77 expression by n-butylidenephthalide has pharmaceuticals on hepatocellular carcinoma cell therapy. Molecular Pharmacology, 74, 1046–1058.PubMedCrossRefGoogle Scholar
  13. Cheng, Y. L., Chang, W. L., Lee, S. C., et al. (2004). Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells via inducing cell cycle arrest and apoptosis. Life Sciences, 75, 1579–1594.PubMedCrossRefGoogle Scholar
  14. Chintharlapalli, S., Burghardt, R., Papineni, S., et al. (2005). Activation of Nur77 by selected 1,1-Bis(3′-indolyl)-1-(p-substituted phenyl) methanes induces apoptosis through nuclear pathways. The Journal of Biological Chemistry, 280, 24903–24914.PubMedCrossRefGoogle Scholar
  15. Choy, Y. M., Leung, K. N., Cho, C. S., et al. (1994). Immunopharmacological studies of low molecular weight polysaccharide from Angelica sinensis. The American Journal of Chinese Medicine, 22, 137–145.PubMedCrossRefGoogle Scholar
  16. Coates, S. S., Lehnert, B. E., Sharma, S., et al. (2007). Beryllium induces premature senescence in human fibroblasts. The Journal of Pharmacology and Experimental Therapeutics, 322, 70–79.PubMedCrossRefGoogle Scholar
  17. Cobb, M. A., Husain, M., Andersen, B. J., et al. (1996). Significance of proliferating cell nuclear antigen in predicting recurrence of intracranial meningioma. Journal of Neurosurgery, 84, 85–90.PubMedCrossRefGoogle Scholar
  18. Counter, C. M., Hahn, W. C., Wei, W., et al. (1998). Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization. Proceedings of the National Academy of Sciences of the United States of America, 95, 14723–14728.PubMedCrossRefGoogle Scholar
  19. Dimri, G. P., Lee, X., Basile, G., et al. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proceedings of the National Academy of Sciences of the United States of America, 92, 9363–9367.PubMedCrossRefGoogle Scholar
  20. Dobashi, Y., Takehana, T., & Ooi, A. (2003). Perspectives on cancer therapy: Cell cycle blockers and perturbators. Current Medicinal Chemistry, 10, 2549–2558.PubMedCrossRefGoogle Scholar
  21. Dong, W. G., Liu, S. P., Zhu, H. H., et al. (2004). Abnormal function of platelets and role of angelica sinensis in patients with ulcerative colitis. World Journal of Gastroenterology: WJG, 10, 606–609.PubMedGoogle Scholar
  22. Elliott, P. J., Hayward, N. J., Huff, M. R., et al. (1996). Unlocking the blood-brain barrier: A role for RMP-7 in brain tumor therapy. Experimental Neurology, 141, 214–224.PubMedCrossRefGoogle Scholar
  23. Flores, I., Benetti, R., & Blasco, M. A. (2006). Telomerase regulation and stem cell behaviour. Current Opinion in Cell Biology, 18, 254–260.PubMedCrossRefGoogle Scholar
  24. Fukuoka, K., Yamagishi, T., Ichihara, T., et al. (2000). Mechanism of action of aragusterol a (YTA0040), a potent anti-tumor marine steroid targeting the G(1) phase of the cell cycle. International Journal of Cancer. Journal International du Cancer, 88, 810–819.PubMedCrossRefGoogle Scholar
  25. Giese, A., Bjerkvig, R., Berens, M. E., et al. (2003). Cost of migration: Invasion of malignant gliomas and implications for treatment. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 21, 1624–1636.CrossRefGoogle Scholar
  26. Han, G., Zhou, Y. F., Zhang, M, S., et al. (2006a). Angelica sinensis down-regulates hydroxyproline and Tgfb1 and provides protection in mice with radiation-induced pulmonary fibrosis. Radiation Research, 165, 546–552.CrossRefGoogle Scholar
  27. Han, Y. H., Cao, X., Lin, B., et al. (2006b). Regulation of Nur77 nuclear export by c-Jun N-terminal kinase and Akt. Oncogene, 25, 2974–2986.CrossRefGoogle Scholar
  28. Herbig, U., Jobling, W. A., Chen, B. P., et al. (2004). Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21 (CIP1), but not p16 (INK4a). Molecular Cell, 14, 501–513.PubMedCrossRefGoogle Scholar
  29. Hu, H., Ahn, N. S., Yang, X., et al. (2002). Ganoderma lucidum extract induces cell cycle arrest and apoptosis in MCF-7 human breast cancer cell. International Journal of Cancer. Journal International du Cancer, 102, 250–253.PubMedCrossRefGoogle Scholar
  30. Jagadeesh, S., Kyo, S., & Banerjee, P. P. (2006). Genistein represses telomerase activity via both transcriptional and posttranslational mechanisms in human prostate cancer cells. Cancer Research, 66, 2107–2115.PubMedCrossRefGoogle Scholar
  31. Kan, W. L., Cho, C. H., Rudd, J. A., et al. (2008). Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells. Journal of Ethnopharmacology, 120, 36–43.PubMedCrossRefGoogle Scholar
  32. Kao, S. T., Yeh, C. C., Hsieh, C. C., et al. (2001). The Chinese medicine Bu-Zhong-Yi-Qi-Tang inhibited proliferation of hepatoma cell lines by inducing apoptosis via G0/G1 arrest. Life Sciences, 691, 485–496.Google Scholar
  33. Keith, W. N., Thomson, C. M., Howcroft, J., et al. (2007). Seeding drug discovery: Integrating telomerase cancer biology and cellular senescence to uncover new therapeutic opportunities in targeting cancer stem cells. Drug Discovery Today, 12, 611–621.PubMedCrossRefGoogle Scholar
  34. Kim, H., Lee, J. E., Kim, B. Y., et al. (2005). Menin represses JunD transcriptional activity in protein kinase C theta-mediated Nur77 expression. Experimental & Molecular Medicine, 37, 466–475.CrossRefGoogle Scholar
  35. Kim, H., Kim, B. Y., Soh, J. W., et al. (2006). A novel function of Nur77: Physical and functional association with protein kinase C. Biochemical and Biophysical Research Communications, 348, 950–956.PubMedCrossRefGoogle Scholar
  36. Kim, S. H., Lee, S. E., Oh, H., et al. (2002). The radioprotective effects of bu-zhong-yi-qi-tang: A prescription of traditional Chinese medicine. The American Journal of Chinese Medicine, 30, 127–137.PubMedCrossRefGoogle Scholar
  37. Ko, W. C., Sheu, J. R., Tzeng, S. H., et al. (1998). The selective antianginal effect without changing blood pressure of butylidenephthalide in conscious rats. Planta Medica, 64, 229–232.PubMedCrossRefGoogle Scholar
  38. Ko, W. C., Liao, C. C., Shih, C. H., et al. (2002). Relaxant effects of butylidenephthalide in isolated dog blood vessels. Planta Medica, 68, 1004–1009.PubMedCrossRefGoogle Scholar
  39. Kornblith, P. L., & Walker, M. (1998). Chemotherapy for malignant gliomas. Journal of Neurosurgery, 68, 1–17.CrossRefGoogle Scholar
  40. Kruse, C. A., Mitchell, D. H., Kleinschmidt-DeMasters, B. K., et al. (1992). Characterization of a continuous human glioma cell line DBTRG-05MG: Growth kinetics, karyotype, receptor expression, and tumor suppressor gene analyses. In vitro Cellular & Developmental Biology: Journal of the Tissue Culture Association, 28A, 609–614.Google Scholar
  41. Kupfersztain, C., Rotem, C., Fagot, R., et al. (2003). The immediate effect of natural plant extract, Angelica sinensis and Matricaria chamomilla (Climex) for the treatment of hot flushes during menopause. A preliminary report. Clinical and Experimental Obstetrics & Gynecology, 30, 203–206.Google Scholar
  42. Kyo, S., Takakura, M., Taira, T., et al. (2000). Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT). Nucleic Acids Research, 28, 669–677.PubMedCrossRefGoogle Scholar
  43. Lee, S. M., Li, M. L., Tse, Y. C., et al. (2002). Paeoniae Radix, a Chinese herbal extract, inhibits hepatoma cells growth by inducing apoptosis in a p53 independent pathway. Life Sciences, 71, 2267–2277.PubMedCrossRefGoogle Scholar
  44. Lee, W. H., Jin, J. S., Tsai, W. C., et al. (2006). Biological inhibitory effects of the Chinese herb danggui on brain astrocytoma. Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology, 73, 141–148.CrossRefGoogle Scholar
  45. Li, H., Kolluri, S. K., Gu, J., et al. (2000). Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3. Science, 289, 1159–1164.PubMedCrossRefGoogle Scholar
  46. Li, Q. X., Ke, N., Sundaram, R., et al. (2006). NR4A1, 2, 3—An orphan nuclear hormone receptor family involved in cell apoptosis and carcinogenesis. Histology and Histopathology, 21, 533–540.PubMedGoogle Scholar
  47. Lin, B., Kolluri, S. K., Lin, F., et al. (2004). Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3. Cell, 116, 527–540.PubMedCrossRefGoogle Scholar
  48. Lin, P. C., Chen, Y. L., Chiu, S. C., et al. (2008). Orphan nuclear receptor, Nurr-77 was a possible target gene of butylidenephthalide chemotherapy on glioblastoma multiform brain tumor. Journal of Neurochemistry, 106, 1017–1026.PubMedCrossRefGoogle Scholar
  49. Liu, C. X., Xiao, P. G., & Li, D. P. (2000). Modern research and application of Chinese medicinal plants (pp. 166–169). Hong Kong Medical: Hong Kong.Google Scholar
  50. Liu, J. P. (2000). Telomerase: Not just black and white, but shades of gray. Molecular Cell Biology Research Communications: MCBRC, 3, 129–135.PubMedCrossRefGoogle Scholar
  51. Liu, S., Wu, Q., Ye, X. F., et al. (2002). Induction of apoptosis by TPA and VP-16 is through translocation of TR3. World Journal of Gastroenterology: WJG, 8, 446–450.PubMedGoogle Scholar
  52. Liu, Y. M., Zhang, J. J., & Jiang, J. (2004). Observation on clinical effect of Angelica injection in treating acute cerebral infarction. Zhongguo Zhong Xi Yi Jie He Za Zhi, 24, 205–208.PubMedGoogle Scholar
  53. Mahaley, M. S., Jr., Mettlin, C., Natarajan, N., et al. (1989). National survey of patterns of care for brain-tumor patients. Journal of Neurosurgery, 71, 826–836.PubMedCrossRefGoogle Scholar
  54. McGovern, P. C., Lautenbach, E., Brennan, P. J., et al. (2003). Risk factors for postcraniotomy surgical site infection after 1,3-bis (2-chloroethyl)-1-nitrosourea (Gliadel) wafer placement. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 36, 759–765.CrossRefGoogle Scholar
  55. Mimura, Y., Kobayashi, S., Naitoh, T., et al. (1995). The structure-activity relationship between synthetic butylidenephthalide derivatives regarding the competence and progression of inhibition in primary cultures proliferation of mouse aorta smooth muscle cells. Biological & Pharmaceutical Bulletin, 18, 1203–1206.CrossRefGoogle Scholar
  56. Mullady, E. L., Millett, W. P., Yoo, H. D., et al. (2004). A phthalide with in vitro growth inhibitory activity from an oidiodendron strain. Journal of Natural Products, 67, 2086–2089.PubMedCrossRefGoogle Scholar
  57. Rajpal, A., Cho, Y. A., Yelent, B., et al. (2003). Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor. The EMBO Journal, 22, 6526–6536.PubMedCrossRefGoogle Scholar
  58. Reed, S. I., Bailly, E., Dulic, V., et al. (1994). G1 control in mammalian cells. Journal of Cell Science. Supplement, 18, 69–73.Google Scholar
  59. Rock, E., & DeMichele, A. (2003). Nutritional approaches to late toxicities of adjuvant chemotherapy in breast cancer survivors. Clinical and Experimental Obstetrics & Gynecology, 30, 203–206.Google Scholar
  60. Ross, B. D., Zhao, Y. J., Neal, E. R., et al. (1998). Contributions of cell kill and posttreatment tumor growth rates to the repopulation of intracerebral 9L tumors after chemotherapy: An MRI study. Proceedings of the National Academy of Sciences of the United States of America, 95, 7012–7017.PubMedCrossRefGoogle Scholar
  61. Santarius, T., Kirsch, M., Rossi, M. L., et al. (1997). Molecular aspects of neuro-oncology. Clinical Neurology and Neurosurgery, 99, 184–195.PubMedCrossRefGoogle Scholar
  62. Schlegel, J., Piontek, G., Kersting, M., et al. (1999). The p16/Cdkn2a/Ink4a gene is frequently deleted in nitrosourea-induced rat glial tumors. Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology, 67, 202–206.CrossRefGoogle Scholar
  63. Schmitt, C. A. (2007). Cellular senescence and cancer treatment. Biochimica et Biophysica Acta, 1775, 5–20.PubMedGoogle Scholar
  64. Schwartsmann, G., Ratain, M. J., Cragg, G. M., et al. (2002). Anticancer drug discovery and development throughout the world. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 20, 47S–59S.Google Scholar
  65. Sekiya, K., Tezuka, Y., Tanaka, K., et al. (2000). Distribution, metabolism and excretion of butylidenephthalide of Ligustici chuanxiong rhizoma in hairless mouse after dermal application. Journal of Ethnopharmacology, 71, 401–409.PubMedCrossRefGoogle Scholar
  66. Shang, P., Qian, A. R., Yang, T. H., et al. (2003). Experimental study of anti-tumor effects of polysaccharides from Angelica sinensis. World Journal of Gastroenterology: WJG, 9, 1963–1967.PubMedGoogle Scholar
  67. Shapiro, W. R., & Green, S. B. (1987). Reevaluating the efficacy of intra-arterial BCNU. Journal of Neurosurgery, 66, 313–315.PubMedGoogle Scholar
  68. Sherr, C. J., & Roberts, J. M. (1995). Inhibitors of mammalian G1 cyclin-dependent kinases. Genes & Development, 9, 1149–1163.CrossRefGoogle Scholar
  69. Subach, B. R., Witham, T. F., Kondziolka, D., et al. (1999). Morbidity and survival after 1,3-bis(2-chloroethyl)-1-nitrosourea wafer implantation for recurrent glioblastoma: A retrospective case-matched cohort series. Neurosurgery, 45, 17–22.PubMedCrossRefGoogle Scholar
  70. Tamargo, R. J., Myseros, J. S., Epstein, J. I., et al. (2003) Interstitial chemotherapy of the 9L gliosarcoma: Controlled release polymers for drug delivery in the brain. Cancer Research, 53, 329–333.Google Scholar
  71. Teng, C. M., Chen, W. Y., Ko, W. C., et al. (1987). Antiplatelet effect of butylidenephthalide. Biochimica et Biophysica Acta, 924, 375–382.PubMedCrossRefGoogle Scholar
  72. Tsai, N. M., Lin, S. Z., Lee, C. C., et al. (2005). The antitumor effects of Angelica sinensis on malignant brain tumors in vitro and in vivo. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 11, 3475–3484.CrossRefGoogle Scholar
  73. Tsai, N. M., Chen, Y. L., Lee, C. C., et al. (2006). The natural compound n-butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo. Journal of Neurochemistry, 99, 1251–1262.PubMedCrossRefGoogle Scholar
  74. Vickers, A. (2002). Botanical medicines for the treatment of cancer: Rationale, overview of current data, and methodological considerations for phase I and II trials. Cancer Investigation, 20, 1069–1079.PubMedCrossRefGoogle Scholar
  75. Wang, H., Chen, R., & Xu, H. (1998). Chemical constituents of radix Angelicae Sinensis. Zhongguo Zhong Yao Za Zhi, 23, 167–168.PubMedGoogle Scholar
  76. Wang, X., Wei, L., Ouyang, J. P., et al. (2001). Effects of an angelica extract on human erythrocyte aggregation, deformation and osmotic fragility. Clinical Hemorheology and Microcirculation, 24, 201–205.PubMedGoogle Scholar
  77. Weih, F., Ryseck, R. P., Chen, L., et al. (1996). Apoptosis of nur77/N10-transgenic thymocytes involves the Fas/Fas ligand pathway. Proceedings of the National Academy of Sciences of the United States of America, 93, 5533–5538.PubMedCrossRefGoogle Scholar
  78. Williams, G. T., & Lau, L. F. (1993). Activation of the inducible orphan receptor gene nur77 by serum growth factors: Dissociation of immediate-early and delayed-early responses. Molecular and Cellular Biology, 13, 6124–6136.PubMedGoogle Scholar
  79. Wilson, A. J., Arango, D., Mariadason, J. M., et al. (2003). TR3/Nur77 in colon cancer cell apoptosis. Cancer Research, 63, 5401–5407.PubMedGoogle Scholar
  80. Winoto, A., & Littman, D. R. (2002). Nuclear hormone receptors in T lymphocytes. Cell, 109(Suppl), S57–S66.PubMedCrossRefGoogle Scholar
  81. Woronicz, J. D., Calnan, B., Ngo, V., et al. (1994). Requirement for the orphan steroid receptor Nur77 in apoptosis of T-cell hybridomas. Nature, 367, 277–281.PubMedCrossRefGoogle Scholar
  82. Wu, K. J., Grandori, C., Amacker, M., et al. (1999). Direct activation of TERT transcription by c-MYC. Nature Genetics, 21, 220–224.PubMedCrossRefGoogle Scholar
  83. Xie, C. H., Zhang, M. S., Zhou, Y. F., et al. (2006). Chinese medicine Angelica sinensis suppresses radiation-induced expression of TNF-alpha and TGF-beta1 in mice. Oncology Reports, 15, 1429–1436.PubMedGoogle Scholar
  84. Xie, F., Li, X., Sun, K., et al. (2001). An experimental study on drugs for improving blood circulation and removing blood stasis in treating mild chronic hepatic damage. Journal of Traditional Chinese Medicine, 21, 225–231.PubMedGoogle Scholar
  85. Xu, J., & Li, G. (2000). Observation on short-term effects of Angelica injection on chronic obstructive pulmonary disease patients with pulmonary hypertension. Zhongguo Zhong Xi Yi Jie He Za Zhi, 20, 187–189.PubMedGoogle Scholar
  86. Yano, H., Mizoguchi, A., Fukuda, K., et al. (1994). The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase. Cancer Research, 54, 448–454.PubMedGoogle Scholar
  87. Ye, Y. N., Koo, M. W., Li, Y., et al. (2001a). Angelica sinensis modulates migration and proliferation of gastric epithelial cells. Life Sciences, 68, 961–968.CrossRefGoogle Scholar
  88. Ye, Y. N., Liu, E. S., Li, Y., et al. (2001b). Protective effect of polysaccharides-enriched fraction from Angelica sinensis on hepatic injury. Life Sciences, 69, 637–646.CrossRefGoogle Scholar
  89. Ye, Y. N., Liu, E. S., Shin, V. Y., et al. (2001c). A mechanistic study of proliferation induced by Angelica sinensis in a normal gastric epithelial cell line. Biochemical Pharmacology, 61, 1439–1448.CrossRefGoogle Scholar
  90. Ye, Y. N., So, H. L., Liu, E. S., et al. (2003). Effect of polysaccharides from Angelica sinensis on gastric ulcer healing. Life Sciences, 72, 925–932.PubMedCrossRefGoogle Scholar
  91. Yim, T. K., Wu, W. K., Pak, W. F., et al. (2000). Myocardial protection against ischaemia-reperfusion injury by a Polygonum multiflorum extract supplemented ‘Dang-Gui decoction for enriching blood,’ a compound formulation, ex vivo. Phytotherapy Research: PTR, 14, 195–199.PubMedCrossRefGoogle Scholar
  92. Yoshikawa, K., Kokudo, N., Hashimoto, T., et al. (2010). Novel phthalide compounds from Sparassis crispa (Hanabiratake), Hanabiratakelide A-C, exhibiting anti-cancer related activity. Biological & Pharmaceutical Bulletin, 33, 1355–1359.CrossRefGoogle Scholar
  93. Youn, H. D., Sun, L., Prywes, R., et al. (1999). Apoptosis of T cells mediated by Ca2+-induced release of the transcription factor MEF2. Science, 286, 790–793.PubMedCrossRefGoogle Scholar
  94. Yu, Y. L., Yu, S. L., Su, K. J., et al. (2010). Extended O6-methylguanine methyltransferase promoter hypermethylation following n-butylidenephthalide combined with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on inhibition of human hepatocellular carcinoma cell growth. Journal of Agricultural and Food Chemistry, 58, 1630–1638.PubMedCrossRefGoogle Scholar
  95. Zhao, K. J., Dong, T. T., Tu, P. F., et al. (2003). Molecular genetic and chemical assessment of radix Angelica (Danggui) in China. Journal of Agricultural and Food Chemistry, 51, 2576–2583.PubMedCrossRefGoogle Scholar
  96. Zhao, L., Zhang, Y., & Xu, Z. X. (1994). Clinical effect and experimental study of xijian tongshuan pill. Zhongguo Zhong Xi Yi Jie He Za Zhi, 14, 71–73.PubMedGoogle Scholar
  97. Zheng, G. Q., Kenney, P. M., Zhang, J., et al. (1993). Chemoprevention of benzo[a]pyrene-induced forestomach cancer in mice by natural phthalides from celery seed oil. Nutrition and Cancer, 19, 77–86.PubMedCrossRefGoogle Scholar
  98. Zhong, Y. H., Han, G., Zhou, Y. F., et al. (2007). Protection of Angelica sinensis against radiation-induced pulmonary fibrosis in mice. Zhonghua Yu Fang Yi Xue Za Zhi, 41, 105–109.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Department of Pathology, Center for NeuropsychiatryChina Medical University and HospitalTaichungTaiwan
  2. 2.Department of Life Science and Graduate Institute of BiotechnologyNational Dong Hwa UniversityShoufengTaiwan
  3. 3.Department of PathologyChina Medical University and HospitalTaiwanRepublic of China

Personalised recommendations