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The Scientific World Journal
Volume 2012 (2012), Article ID 708292, 31 pages
http://dx.doi.org/10.1100/2012/708292
Review Article

Interaction of Herbal Compounds with Biological Targets: A Case Study with Berberine

1Department of General Surgery, The First People’s Hospital of Shunde, Southern Medical University, Shunde, Guangdong 528300, China
2School of Health Sciences and Health Innovations Research Institute, RMIT University, Bundoora, VIC 3083, Australia
3Department of Surgery, The Third Hospital of Nanchang, Jiangxi, Nanchang 330009, China
4Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Boulevard, MDC 30, Tampa, FL 33612, USA

Received 7 June 2012; Accepted 8 July 2012

Academic Editors: H.-W. Chang, L.-Y. Chuang, and S. Yasmin

Copyright © 2012 Xiao-Wu Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. J. Zheng, L. Y. Han, C. W. Yap, B. Xie, and Y. Z. Chen, “Trends in exploration of therapeutic targets,” Drug News and Perspectives, vol. 18, no. 2, pp. 109–127, 2005. View at Publisher · View at Google Scholar · View at Scopus
  2. B. Bryant and K. Knights, Pharmacology for Health Professionals, Mosby Elsevier, Chatswood, Australia, 3rd edition, 2011.
  3. A. L. Hopkins and C. R. Groom, “The druggable genome,” Nature Reviews Drug Discovery, vol. 1, no. 9, pp. 727–730, 2002. View at Google Scholar · View at Scopus
  4. C. J. Zheng, L. Y. Han, C. W. Yap, Z. L. Ji, Z. W. Cao, and Y. Z. Chen, “Therapeutic targets: progress of their exploration and investigation of their characteristics,” Pharmacological Reviews, vol. 58, no. 2, pp. 259–279, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. J. Drews, “Genomic sciences and the medicine of tomorrow,” Nature Biotechnology, vol. 14, no. 11, pp. 1516–1518, 1996. View at Google Scholar · View at Scopus
  6. J. Drews and S. Ryser, “The role of innovation in drug development,” Nature Biotechnology, vol. 15, no. 13, pp. 1318–1319, 1997. View at Google Scholar · View at Scopus
  7. C. A. Lipinski, F. Lombardo, B. W. Dominy, and P. J. Feeney, “Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings,” Advanced Drug Delivery Reviews, vol. 46, no. 1–3, pp. 3–26, 2001. View at Publisher · View at Google Scholar · View at Scopus
  8. X. Chen, C. J. Zheng, L. Y. Han, B. Xie, and Y. Z. Chen, “Trends in the exploration of therapeutic targets for the treatment of endocrine, metabolic and immune disorders,” Endocrine, Metabolic and Immune Disorders, vol. 7, no. 3, pp. 225–231, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. X. Chen, Z. L. Ji, and Y. Z. Chen, “TTD: therapeutic target database,” Nucleic Acids Research, vol. 30, no. 1, pp. 412–415, 2002. View at Google Scholar · View at Scopus
  10. J. Qiu, “Traditional medicine: a culture in the balance,” Nature, vol. 448, no. 7150, pp. 126–128, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. R. Stone, “Biochemistry: lifting the veil on traditional Chinese medicine,” Science, vol. 319, no. 5864, pp. 709–710, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. P. Barnes, E. Powell-Griner, K. McFann, and R. Nahin, “Complementary and alternative medicine use among adults: United States, 2002,” Advanced Data From Vital and Health Statistics 343, National Center for Health Statistics, Hyattsville, Md, USA.
  13. E. Ernst and M. H. Pittler, “Herbal medicine,” Medical Clinics of North America, vol. 86, no. 1, pp. 149–161, 2002. View at Publisher · View at Google Scholar · View at Scopus
  14. J. Yin, H. Xing, and J. Ye, “Efficacy of berberine in patients with type 2 diabetes mellitus,” Metabolism: Clinical and Experimental, vol. 57, no. 5, pp. 712–717, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Grycová, J. Dostál, and R. Marek, “Quaternary protoberberine alkaloids,” Phytochemistry, vol. 68, no. 2, pp. 150–175, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. W. Xie and L. Du, “Diabetes is an inflammatory disease: evidence from traditional Chinese medicines,” Diabetes, Obesity and Metabolism, vol. 13, no. 4, pp. 289–301, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. B. Schoenbart and S. Ellen, “Traditional Chinese Medicine for the Digestive System,” 2007, http://health.howstuffworks.com/wellness/natural-medicine/chinese/traditional-chinese-medicine-for-the-digestive-system.htm.
  18. Y. T. Ho, C. C. Lu, J. S. Yang et al., “Berberine induced apoptosis via promoting the expression of caspase-8, -9 and -3, apoptosis-inducing factor and endonuclease G in SCC-4 human tongue squamous carcinoma cancer cells,” Anticancer Research, vol. 29, no. 10, pp. 4063–4070, 2009. View at Google Scholar · View at Scopus
  19. W. H. Hsu, Y. S. Hsieh, H. C. Kuo et al., “Berberine induces apoptosis in SW620 human colonic carcinoma cells through generation of reactive oxygen species and activation of JNK/p38 MAPK and FasL,” Archives of Toxicology, vol. 81, no. 10, pp. 719–728, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. S. K. Katiyar, S. M. Meeran, N. Katiyar, and S. Akhtar, “P53 cooperates berberine-induced growth inhibition and apoptosis of non-small cell human lung cancer cells in vitro and tumor xenograft growth in vivo,” Molecular Carcinogenesis, vol. 48, no. 1, pp. 24–37, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. S. K. Mantena, S. D. Sharma, and S. K. Katiyar, “Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP,” Carcinogenesis, vol. 27, no. 10, pp. 2018–2027, 2006. View at Publisher · View at Google Scholar · View at Scopus
  22. K. K. W. Auyeung and J. K. S. Ko, “Coptis chinensis inhibits hepatocellular carcinoma cell growth through nonsteroidal anti-inflammatory drug-activated gene activation,” International Journal of Molecular Medicine, vol. 24, no. 4, pp. 571–577, 2009. View at Publisher · View at Google Scholar · View at Scopus
  23. K. Inoue, U. Kulsum, S. A. Chowdhury et al., “Tumor-specific cytotoxicity and apoptosis-inducing activity of berberines,” Anticancer Research, vol. 25, no. 6, pp. 4053–4059, 2005. View at Google Scholar · View at Scopus
  24. J. P. Lin, J. S. Yang, J. H. Lee, W. T. Hsieh, and J. G. Chung, “Berberine induces cell cycle arrest and apoptosis in human gastric carcinoma SNU-5 cell line,” World Journal of Gastroenterology, vol. 12, no. 1, pp. 21–28, 2006. View at Google Scholar · View at Scopus
  25. M. S. Choi, D. Y. Yuk, J. H. Oh et al., “Berberine inhibits human neuroblastoma cell growth through induction of p53-dependent apoptosis,” Anticancer Research, vol. 28, no. 6, pp. 3777–3784, 2008. View at Google Scholar · View at Scopus
  26. F. Tang, D. Wang, C. Duan et al., “Berberine inhibits metastasis of nasopharyngeal carcinoma 5-8F cells by targeting rho kinase-mediated ezrin phosphorylation at threonine 567,” Journal of Biological Chemistry, vol. 284, no. 40, pp. 27456–27466, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. K. Fukuda, Y. Hibiya, M. Mutoh, M. Koshiji, S. Akao, and H. Fujiwara, “Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells,” Journal of Ethnopharmacology, vol. 66, no. 2, pp. 227–233, 1999. View at Publisher · View at Google Scholar · View at Scopus
  28. J. G. Chung, G. W. Chen, C. F. Hung et al., “Effects of berberine on arylamine N-acetyltransferase activity and 2-aminofluorene-DNA adduct formation in human leukemia cells,” American Journal of Chinese Medicine, vol. 28, no. 2, pp. 227–238, 2000. View at Google Scholar · View at Scopus
  29. M. S. Choi, J. H. Oh, S. M. Kim et al., “Berberine inhibits p53-dependent cell growth through induction of apoptosis of prostate cancer cells,” International Journal of Oncology, vol. 34, no. 5, pp. 1221–1230, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. S. K. Mantena, S. D. Sharma, and S. K. Katiyar, “Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells,” Molecular Cancer Therapeutics, vol. 5, no. 2, pp. 296–308, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. C. C. Lin, S. T. Kao, G. W. Chen, H. C. Ho, and J. G. Chung, “Apoptosis of human leukemia HL-60 cells and murine leukemia WEHI-3 cells induced by berberine through the activation of caspase-3,” Anticancer Research, vol. 26, no. 1, pp. 227–242, 2006. View at Google Scholar · View at Scopus
  32. Y. Luo, Y. Hao, T. P. Shi, W. W. Deng, and N. Li, “Berberine inhibits cyclin D1 expression via suppressed binding of AP-1 transcription factors to CCND1 AP-1 motif,” Acta Pharmacologica Sinica, vol. 29, no. 5, pp. 628–633, 2008. View at Publisher · View at Google Scholar · View at Scopus
  33. S. Jantova, L. Cipak, and S. Letasiova, “Berberine induces apoptosis through a mitochondrial/caspase pathway in human promonocytic U937 cells,” Toxicology in Vitro, vol. 21, no. 1, pp. 25–31, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. Y. T. Ho, J. S. Yang, T. C. Li et al., “Berberine suppresses in vitro migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-κB, u-PA and MMP-2 and -9,” Cancer Letters, vol. 279, no. 2, pp. 155–162, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. H. Li, L. Guo, S. Jie et al., “Berberine inhibits SDF-1-induced AML cells and leukemic stem cells migration via regulation of SDF-1 level in bone marrow stromal cells,” Biomedicine and Pharmacotherapy, vol. 62, no. 9, pp. 573–578, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. G. C. M. Bruschi, C. C. De Souza, M. R. V. Z. K. Fagundes et al., “Sensitivity to camptothecin in Aspergillus nidulans identifies a novel gene, scaA+, related to the cellular DNA damage response,” Molecular and General Genetics, vol. 265, no. 2, pp. 264–275, 2001. View at Google Scholar · View at Scopus
  37. Y. Chen, Y. Li, Y. Wang, Y. Wen, and C. Sun, “Berberine improves free-fatty-acid-induced insulin resistance in L6 myotubes through inhibiting peroxisome proliferator-activated receptor γ and fatty acid transferase expressions,” Metabolism: Clinical and Experimental, vol. 58, no. 12, pp. 1694–1702, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. W. J. Kong, H. Zhang, D. Q. Song et al., “Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression,” Metabolism: Clinical and Experimental, vol. 58, no. 1, pp. 109–119, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. G. Y. Pan, Z. J. Huang, G. J. Wang et al., “The antihyperglycaemic activity of berberine arises from a decrease of glucose absorption,” Planta Medica, vol. 69, no. 7, pp. 632–636, 2003. View at Publisher · View at Google Scholar · View at Scopus
  40. Z. S. Wang, F. E. Lu, L. J. Xu, and H. Dong, “Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells,” Acta Pharmacologica Sinica, vol. 31, no. 5, pp. 578–584, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. Y. Yu, L. Liu, X. Wang et al., “Modulation of glucagon-like peptide-1 release by berberine: in vivo and in vitro studies,” Biochemical Pharmacology, vol. 79, no. 7, pp. 1000–1006, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. J. Yu, B. K. Piao, Y. X. Pei, X. Qi, and B. J. Hua, “Protective effects of tetrahydropalmatine against γ-radiation induced damage to human endothelial cells,” Life Sciences, vol. 87, no. 1-2, pp. 55–63, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. L. Liu, Y. L. Yu, J. S. Yang et al., “Berberine suppresses intestinal disaccharidases with beneficial metabolic effects in diabetic states, evidences from in vivo and in vitro study,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 381, no. 4, pp. 371–381, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. L. Q. Tang, W. Wei, L. M. Chen, and S. Liu, “Effects of berberine on diabetes induced by alloxan and a high-fat/high-cholesterol diet in rats,” Journal of Ethnopharmacology, vol. 108, no. 1, pp. 109–115, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. C. Wang, J. Li, X. Lv et al., “Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin,” European Journal of Pharmacology, vol. 620, no. 1–3, pp. 131–137, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. X. Xia, J. Yan, Y. Shen et al., “Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis,” PLoS ONE, vol. 6, no. 2, Article ID e16556, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. B. L. Wajchenberg, “β-cell failure in diabetes and preservation by clinical treatment,” Endocrine Reviews, vol. 28, no. 2, pp. 187–218, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. D. Giugliano, E. Standl, T. Vilsbøll et al., “Is the current therapeutic armamentarium in diabetes enough to control the epidemic and its consequences? What are the current shortcomings?” Acta Diabetologica, vol. 46, no. 3, pp. 173–181, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. R. J. Heine, M. Diamant, J. C. Mbanya, and D. M. Nathan, “Management of hyperglycaemia in type 2 diabetes,” British Medical Journal, vol. 333, no. 7580, pp. 1200–1204, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. S. S. Lu, Y. L. Yu, H. J. Zhu et al., “Berberine promotes glucagon-like peptide-1 (7-36) amide secretion in streptozotocin-induced diabetic rats,” Journal of Endocrinology, vol. 200, no. 2, pp. 159–165, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Zhou, S. Zhou, J. Tang et al., “Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats,” European Journal of Pharmacology, vol. 606, no. 1–3, pp. 262–268, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. J. Hone, D. Accili, L. I. Al-Gazali, G. Lestringant, T. Orban, and S. I. Taylor, “Homozygosity for a new mutation (Ile119→Met) in the insulin receptor gene in five sibs with familial insulin resistance,” Journal of Medical Genetics, vol. 31, no. 9, pp. 715–716, 1994. View at Google Scholar · View at Scopus
  53. J. J. Holst, “The physiology of glucagon-like peptide 1,” Physiological Reviews, vol. 87, no. 4, pp. 1409–1439, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. Y. S. Lee, W. S. Kim, K. H. Kim et al., “Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states,” Diabetes, vol. 55, no. 8, pp. 2256–2264, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. S. H. Leng, F. E. Lu, and L. J. Xu, “Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion,” Acta Pharmacologica Sinica, vol. 25, no. 4, pp. 496–502, 2004. View at Google Scholar · View at Scopus
  56. Y. Wang, T. Campbell, B. Perry, C. Beaurepaire, and L. Qin, “Hypoglycemic and insulin-sensitizing effects of berberine in high-fat diet- and streptozotocin-induced diabetic rats,” Metabolism: Clinical and Experimental, vol. 60, no. 2, pp. 298–305, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. S. F. Dong, Y. Hong, M. Liu et al., “Berberine attenuates cardiac dysfunction in hyperglycemic and hypercholesterolemic rats,” European Journal of Pharmacology, vol. 660, no. 2-3, pp. 368–374, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. J. Y. Zhou, S. W. Zhou, K. B. Zhang et al., “Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats,” Biological and Pharmaceutical Bulletin, vol. 31, no. 6, pp. 1169–1176, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. X. Chang, H. Yan, J. Fei et al., “Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats,” Journal of Lipid Research, vol. 51, no. 9, pp. 2504–2515, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. S. Manley, “Haemoglobin A1c—a marker for complications of type 2 diabetes: the experience from the UK Prospective Diabetes Study (UKPDS),” Clinical Chemistry and Laboratory Medicine, vol. 41, no. 9, pp. 1182–1190, 2003. View at Publisher · View at Google Scholar · View at Scopus
  61. Y. Zhang, X. Li, D. Zou et al., “Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine,” The Journal of Clinical Endocrinology & Metabolism, vol. 93, pp. 2559–2565, 2008. View at Publisher · View at Google Scholar
  62. H. Zhang, J. Wei, R. Xue et al., “Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression,” Metabolism: Clinical and Experimental, vol. 59, no. 2, pp. 285–292, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. A. Emslie-Smith, D. I. R. Boyle, J. M. M. Evans, F. Sullivan, and A. D. Morris, “Contraindications to metformin therapy in patients with type 2 diabetes—a population-based study of adherence to prescribing guidelines,” Diabetic Medicine, vol. 18, no. 6, pp. 483–488, 2001. View at Publisher · View at Google Scholar · View at Scopus
  64. T. M. Ehrman, D. J. Barlow, and P. J. Hylands, “Phytochemical databases of Chinese herbal constituents and bioactive plant compounds with known target specificities,” Journal of Chemical Information and Modeling, vol. 47, no. 2, pp. 254–263, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. D. J. Newman, G. M. Cragg, and K. M. Snader, “Natural products as sources of new drugs over the period 1981–2002,” Journal of Natural Products, vol. 66, no. 7, pp. 1022–1037, 2003. View at Publisher · View at Google Scholar · View at Scopus
  66. S. Frantz, “Playing dirty,” Nature, vol. 437, no. 7061, pp. 942–943, 2005. View at Publisher · View at Google Scholar · View at Scopus
  67. S. L. Schreiber, “Target-oriented and diversity-oriented organic synthesis in drug discovery,” Science, vol. 287, no. 5460, pp. 1964–1969, 2000. View at Publisher · View at Google Scholar · View at Scopus
  68. J. Drews, “Drug discovery: a historical perspective,” Science, vol. 287, no. 5460, pp. 1960–1964, 2000. View at Publisher · View at Google Scholar · View at Scopus
  69. J. L. Gao, J. M. Shi, S. M. Y. Lee, Q. W. Zhang, and Y. T. Wang, “Angiogenic pathway inhibition of Corydalis yanhusuo and berberine in human umbilical vein endothelial cells,” Oncology Research, vol. 17, no. 11-12, pp. 519–526, 2009. View at Google Scholar · View at Scopus
  70. J. P. Lin, J. S. Yang, C. C. Wu et al., “Berberine induced down-regulation of matrix metalloproteinase-1, -2 and -9 in human gastric cancer cells (SNU-5) in vitro,” In Vivo, vol. 22, no. 2, pp. 223–230, 2008. View at Google Scholar · View at Scopus
  71. T. H. Lin, H. C. Kuo, F. P. Chou, and F. J. Lu, “Berberine enhances inhibition of glioma tumor cell migration and invasiveness mediated by arsenic trioxide,” BMC Cancer, vol. 8, article 58, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. P. L. Peng, Y. S. Hsieh, C. J. Wang, J. L. Hsu, and F. P. Chou, “Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2,” Toxicology and Applied Pharmacology, vol. 214, no. 1, pp. 8–15, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. J. M. Brusq, N. Ancellin, P. Grondin et al., “Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine,” Journal of Lipid Research, vol. 47, no. 6, pp. 1281–1288, 2006. View at Publisher · View at Google Scholar · View at Scopus
  74. C. W. Chi, Y. F. Chang, T. W. Chao et al., “Flowcytometric analysis of the effect of berberine on the expression of glucocorticoid receptors in human hepatoma HepG2 cells,” Life Sciences, vol. 54, no. 26, pp. 2099–2107, 1994. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Asai, N. Iwata, A. Yoshikawa et al., “Berberine alters the processing of Alzheimer's amyloid precursor protein to decrease Aβ secretion,” Biochemical and Biophysical Research Communications, vol. 352, no. 2, pp. 498–502, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. J. M. Hwang, H. C. Kuo, T. H. Tseng, J. Y. Liu, and C. Y. Chu, “Berberine induces apoptosis through a mitochondria/caspases pathway in human hepatoma cells,” Archives of Toxicology, vol. 80, no. 2, pp. 62–73, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. M. K. Pandey, B. Sung, A. B. Kunnumakkara, G. Sethi, M. M. Chaturvedi, and B. B. Aggarwal, “Berberine modifies cysteine 179 of IκBα kinase, suppresses nuclear factor-κB-regulated antiapoptotic gene products, and potentiates apoptosis,” Cancer Research, vol. 68, no. 13, pp. 5370–5379, 2008. View at Publisher · View at Google Scholar · View at Scopus
  78. C. C. Lin, L. T. Ng, F. F. Hsu, D. E. Shieh, and L. C. Chiang, “Cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents (berberine, coptisine and icariin) on hepatoma and leukaemia cell growth,” Clinical and Experimental Pharmacology and Physiology, vol. 31, no. 1-2, pp. 65–69, 2004. View at Publisher · View at Google Scholar · View at Scopus
  79. J. G. Lin, J. G. Chung, L. T. Wu, G. W. Chen, H. L. Chang, and T. F. Wang, “Effects of berberine on arylamine n-acetyltransferase activity in human colon tumor cells,” American Journal of Chinese Medicine, vol. 27, no. 2, pp. 265–275, 1999. View at Google Scholar · View at Scopus
  80. D. Y. Wang, C. C. Yeh, J. H. Lee, C. F. Hung, and J. G. Chung, “Berberine inhibited arylamine N-acetyltransferase activity and gene expression and DNA adduct formation in human malignant astrocytoma (G9T/VGH) and brain glioblastoma multiforms (GBM 8401) cells,” Neurochemical Research, vol. 27, no. 9, pp. 883–889, 2002. View at Publisher · View at Google Scholar · View at Scopus
  81. J. B. Kim, E. Ko, W. Han, I. Shin, S. Y. Park, and D. Y. Non, “Berberine diminishes the side population and ABCG2 transporter expression in MCF-7 breast cancer cells,” Planta Medica, vol. 74, no. 14, pp. 1693–1700, 2008. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Liu, C. He, K. Zhou, J. Wang, and J. X. Kang, “Coptis extracts enhance the anticancer effect of estrogen receptor antagonists on human breast cancer cells,” Biochemical and Biophysical Research Communications, vol. 378, no. 2, pp. 174–178, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. X. H. Wang, S. M. Jiang, and Q. W. Sun, “Effects of berberine on human rheumatoid arthritis fibroblast-like synoviocytes,” Experimental Biology and Medicine, vol. 236, no. 7, pp. 859–866, 2011. View at Publisher · View at Google Scholar · View at Scopus
  84. C. C. Lin, S. Y. Lin, J. G. Chung, J. P. Lin, G. W. Chen, and S. T. Kao, “Down-regulation of cyclin B1 and Up-regulation of Wee1 by berberine promotes entry of leukemia cells into the G2/M-phase of the cell cycle,” Anticancer Research, vol. 26, no. 2, pp. 1097–1104, 2006. View at Google Scholar · View at Scopus
  85. J. P. Lin, J. S. Yang, N. W. Chang et al., “GADD153 mediates berberine-induced apoptosis in human cervical cancer Ca ski cells,” Anticancer Research, vol. 27, no. 5, pp. 3379–3386, 2007. View at Google Scholar · View at Scopus
  86. Y. T. Ho, J. S. Yang, C. C. Lu et al., “Berberine inhibits human tongue squamous carcinoma cancer tumor growth in a murine xenograft model,” Phytomedicine, vol. 16, no. 9, pp. 887–890, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. S. M. Meeran, S. Katiyar, and S. K. Katiyar, “Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation,” Toxicology and Applied Pharmacology, vol. 229, no. 1, pp. 33–43, 2008. View at Publisher · View at Google Scholar · View at Scopus
  88. S. Nishida, S. Kikuichi, S. Yoshioka et al., “Induction of apoptosis in HL-60 cells treated with medicinal herbs,” American Journal of Chinese Medicine, vol. 31, no. 4, pp. 551–562, 2003. View at Publisher · View at Google Scholar · View at Scopus
  89. K. Yan, C. Zhang, J. Feng et al., “Induction of G1 cell cycle arrest and apoptosis by berberine in bladder cancer cells,” European Journal of Pharmacology, vol. 661, no. 1–3, pp. 1–7, 2011. View at Publisher · View at Google Scholar · View at Scopus
  90. K. S. Eom, J. M. Hong, M. J. Youn et al., “Berberine induces G1 arrest and apoptosis in human glioblastoma T98G cells through mitochondrial/caspases pathway,” Biological and Pharmaceutical Bulletin, vol. 31, no. 4, pp. 558–562, 2008. View at Publisher · View at Google Scholar · View at Scopus
  91. C. M. Tsang, E. P. W. Lau, K. Di et al., “Berberine inhibits Rho GTPases and cell migration at low doses but induces G2 arrest and apoptosis at high doses in human cancer cells,” International Journal of Molecular Medicine, vol. 24, no. 1, pp. 131–138, 2009. View at Publisher · View at Google Scholar · View at Scopus
  92. Z. Liu, Q. Liu, B. Xu et al., “Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage,” Mutation Research, vol. 662, no. 1-2, pp. 75–83, 2009. View at Publisher · View at Google Scholar · View at Scopus
  93. H. S. Cui, S. Hayasaka, X. Y. Zhang, Y. Hayasaka, Z. L. Chi, and L. S. Zheng, “Effect of berberine on interleukin 8 and monocyte chemotactic protein 1 expression in a human retinal pigment epithelial cell line,” Ophthalmic Research, vol. 38, no. 3, pp. 149–157, 2006. View at Publisher · View at Google Scholar · View at Scopus
  94. R. Piyanuch, M. Sukhthankar, G. Wandee, and S. J. Baek, “Berberine, a natural isoquinoline alkaloid, induces NAG-1 and ATF3 expression in human colorectal cancer cells,” Cancer Letters, vol. 258, no. 2, pp. 230–240, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. M. Khan, B. Giessrigl, C. Vonach et al., “Berberine and a Berberis lycium extract inactivate Cdc25A and induce α-tubulin acetylation that correlate with HL-60 cell cycle inhibition and apoptosis,” Mutation Research, vol. 683, no. 1-2, pp. 123–130, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. P. Chatterjee and M. R. Franklin, “Human cytochrome P450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components,” Drug Metabolism and Disposition, vol. 31, no. 11, pp. 1391–1397, 2003. View at Publisher · View at Google Scholar · View at Scopus
  97. X. Wu, Q. Li, H. Xin, A. Yu, and M. Zhong, “Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study,” European Journal of Clinical Pharmacology, vol. 61, no. 8, pp. 567–572, 2005. View at Publisher · View at Google Scholar · View at Scopus
  98. J. W. Budzinski, V. L. Trudeau, C. E. Drouin, M. Panahi, J. T. Arnason, and B. C. Foster, “Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products,” Canadian Journal of Physiology and Pharmacology, vol. 85, no. 9, pp. 966–978, 2007. View at Publisher · View at Google Scholar · View at Scopus
  99. I. M. Al-Masri, M. K. Mohammad, and M. O. Tahaa, “Inhibition of dipeptidyl peptidase IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine,” Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 24, no. 5, pp. 1061–1066, 2009. View at Publisher · View at Google Scholar · View at Scopus
  100. L. Xu, Y. Liu, and X. He, “Inhibitory effects of berberine on the activation and cell cycle progression of human peripheral lymphocytes,” Cellular & Molecular Immunology, vol. 2, no. 4, pp. 295–300, 2005. View at Google Scholar · View at Scopus
  101. H. Li, B. Dong, S. W. Park, H. S. Lee, W. Chen, and J. Liu, “Hepatocyte nuclear factor 1α plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine,” Journal of Biological Chemistry, vol. 284, no. 42, pp. 28885–28895, 2009. View at Publisher · View at Google Scholar · View at Scopus
  102. S. Lin, S. C. Tsai, C. C. Lee, B. W. Wang, J. Y. Liou, and K. G. Shyu, “Berberine inhibits HIF-1α expression via enhanced proteolysis,” Molecular Pharmacology, vol. 66, no. 3, pp. 612–619, 2004. View at Google Scholar · View at Scopus
  103. C. L. Kuo, C. W. Chi, and T. Y. Liu, “Modulation of apoptosis by berberine through inhibition of cyclooxygenase-2 and Mcl-1 expression in oral cancer cells,” In Vivo, vol. 19, no. 1, pp. 247–252, 2005. View at Google Scholar · View at Scopus
  104. C. H. Lee, J. C. Chen, C. Y. Hsiang, S. L. Wu, H. C. Wu, and T. Y. Ho, “Berberine suppresses inflammatory agents-induced interleukin-1β and tumor necrosis factor-α productions via the inhibition of IκB degradation in human lung cells,” Pharmacological Research, vol. 56, no. 3, pp. 193–201, 2007. View at Publisher · View at Google Scholar · View at Scopus
  105. S. Kim, Y. Kim, J. E. Kim, K. H. Cho, and J. H. Chung, “Berberine inhibits TPA-induced MMP-9 and IL-6 expression in normal human keratinocytes,” Phytomedicine, vol. 15, no. 5, pp. 340–347, 2008. View at Publisher · View at Google Scholar · View at Scopus
  106. P. Abidi, Y. Zhou, J. D. Jiang, and J. Liu, “Extracellular signal-regulated kinase-dependent stabilization of hepatic low-density lipoprotein receptor mRNA by herbal medicine berberine,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 10, pp. 2170–2176, 2005. View at Publisher · View at Google Scholar · View at Scopus
  107. J. Cameron, T. Ranheim, M. A. Kulseth, T. P. Leren, and K. E. Berge, “Berberine decreases PCSK9 expression in HepG2 cells,” Atherosclerosis, vol. 201, no. 2, pp. 266–273, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. Y. Li, G. Ren, Y. X. Wang et al., “Bioactivities of berberine metabolites after transformation through CYP450 isoenzymes,” Journal of Translational Medicine, vol. 9, article 62, 2011. View at Publisher · View at Google Scholar · View at Scopus
  109. S. Kim and J. H. Chung, “Berberine prevents UV-induced MMP-1 and reduction of type I procollagen expression in human dermal fibroblasts,” Phytomedicine, vol. 15, no. 9, pp. 749–753, 2008. View at Publisher · View at Google Scholar · View at Scopus
  110. Y. Guo, Q. Z. Wang, F. M. Li, X. Jiang, Y. F. Zuo, and L. Wang, “Biochemical pathways in the antiatherosclerotic effect of berberine,” Chinese Medical Journal, vol. 121, no. 13, pp. 1197–1203, 2008. View at Google Scholar · View at Scopus
  111. Y. D. Min, M. C. Yang, K. H. Lee, K. R. Kim, S. U. Choi, and K. R. Lee, “Protoberberine alkaloids and their reversal activity of P-gp expressed multidrug resistance (MDR) from the rhizome of Coptis japonica makino,” Archives of Pharmacal Research, vol. 29, no. 9, pp. 757–761, 2006. View at Google Scholar · View at Scopus
  112. S. Lee, H. J. Lim, J. H. Park, K. S. Lee, Y. Jang, and H. Y. Park, “Berberine-induced LDLR up-regulation involves JNK pathway,” Biochemical and Biophysical Research Communications, vol. 362, pp. 853–857, 2007. View at Publisher · View at Google Scholar · View at Scopus
  113. C. Y. Hsiang, S. L. Wu, S. E. Cheng, and T. Y. Ho, “Acetaldehyde-induced interleukin-1β and tumor necrosis factor-α production is inhibited by berberine through nuclear factor-κB signaling pathway in HepG2 cells,” Journal of Biomedical Science, vol. 12, no. 5, pp. 791–801, 2005. View at Publisher · View at Google Scholar · View at Scopus
  114. J. P. Hu, K. Nishishita, E. Sakai et al., “Berberine inhibits RANKL-induced osteoclast formation and survival through suppressing the NF-κB and Akt pathways,” European Journal of Pharmacology, vol. 580, no. 1-2, pp. 70–79, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. D. C. Chao, L. J. Lin, S. T. Kao et al., “Inhibitory effects of Zuo-Jin-Wan and its alkaloidal ingredients on activator protein 1, nuclear factor-κB, and cellular transformation in HepG2 cells,” Fitoterapia, vol. 82, no. 4, pp. 696–703, 2011. View at Publisher · View at Google Scholar · View at Scopus
  116. H. L. Wu, C. Y. Hsu, W. H. Liu, and B. Y. Yung, “Berberine-induced apoptosis of human leukemia HL-60 cells is associated with down-regulation of nucleophosmin/B23 and telomerase activity,” International Journal of Cancer, vol. 81, pp. 923–929, 1999. View at Google Scholar
  117. Y. Li, P. Wang, Y. Zhuang et al., “Activation of AMPK by berberine promotes adiponectin multimerization in 3T3-L1 adipocytes,” FEBS Letters, vol. 585, no. 12, pp. 1735–1740, 2011. View at Publisher · View at Google Scholar · View at Scopus
  118. C. L. Kuo, C. W. Chi, and T. Y. Liu, “The anti-inflammatory potential of berberine in vitro and in vivo,” Cancer Letters, vol. 203, no. 2, pp. 127–137, 2004. View at Publisher · View at Google Scholar · View at Scopus
  119. Y. S. Hsieh, W. H. Kuo, T. W. Lin et al., “Protective effects of berberine against low-density lipoprotein (LDL) oxidation and oxidized LDL-induced cytotoxicity on endothelial cells,” Journal of Agricultural and Food Chemistry, vol. 55, no. 25, pp. 10437–10445, 2007. View at Publisher · View at Google Scholar · View at Scopus
  120. W. L. Hyun, H. S. Jung, H. N. Kim et al., “Berberine promotes osteoblast differentiation by Runx2 activation with p38 MAPK,” Journal of Bone and Mineral Research, vol. 23, no. 8, pp. 1227–1237, 2008. View at Publisher · View at Google Scholar · View at Scopus
  121. Y. Qin, J. Y. Pang, W. H. Chen, Z. Z. Zhao, L. Liu, and Z. H. Jiang, “Inhibition of DNA topoisomerase I by natural and synthetic mono- and dimeric protoberberine alkaloids,” Chemistry and Biodiversity, vol. 4, no. 3, pp. 481–487, 2007. View at Publisher · View at Google Scholar · View at Scopus
  122. K. Fukuda, Y. Hibiya, M. Mutoh, M. Koshiji, S. Akao, and H. Fujiwara, “Inhibition of activator protein 1 activity by berberine in human hepatoma cells,” Planta Medica, vol. 65, no. 4, pp. 381–383, 1999. View at Google Scholar · View at Scopus
  123. S. Kim, H. C. Jae, B. K. Jong et al., “Berberine suppresses TNF-α-induced MMP-9 and cell invasion through inhibition of AP-1 activity in MDA-MB-231 human breast cancer cells,” Molecules, vol. 13, no. 12, pp. 2975–2985, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. S. Mahata, A. C. Bharti, S. Shukla, A. Tyagi, S. A. Husain, and B. C. Das, “Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells,” Molecular Cancer, vol. 10, article 39, 2011. View at Publisher · View at Google Scholar · View at Scopus
  125. F. L. Chen, Z. H. Yang, Y. Liu et al., “Berberine inhibits the expression of TNFalpha, MCP-1, and IL-6 in AcLDL-stimulated macrophages through PPARgamma pathway,” Endocrine, vol. 33, no. 3, pp. 331–337, 2008. View at Publisher · View at Google Scholar · View at Scopus