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Evidence-Based Complementary and Alternative Medicine
Volume 2015, Article ID 980190, 19 pages
http://dx.doi.org/10.1155/2015/980190
Research Article

Systems Pharmacology Dissecting Holistic Medicine for Treatment of Complex Diseases: An Example Using Cardiocerebrovascular Diseases Treated by TCM

1Evidence-Based Medicine Centre, Tianjin University of Traditional Chinese Medicine, The First Affiliated Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
2Bioinformatics Center, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi 712100, China
3School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China
4State Key Laboratory of New-Tech for Chinese Medicine Pharmaceutical Process, Lianyungang, Jiangsu 22001, China

Received 10 February 2015; Revised 8 April 2015; Accepted 15 April 2015

Academic Editor: Yew-Min Tzeng

Copyright © 2015 Yonghua Wang 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. S. Ventegodt, N. J. Andersen, and J. Merrick, “Holistic medicine: scientific challenges,” TheScientificWorldJOURNAL, vol. 3, pp. 1108–1116, 2003. View at Publisher · View at Google Scholar
  2. Y. Wang and A. Xu, “Zheng: a systems biology approach to diagnosis and treatments,” Science, vol. 346, no. 6216, supplement, pp. S13–S15, 2014. View at Google Scholar
  3. W. M. Gesler, “Therapeutic landscapes: medical issues in light of the new cultural geography,” Social Science & Medicine, vol. 34, no. 7, pp. 735–746, 1992. View at Publisher · View at Google Scholar · View at Scopus
  4. C. Auffray, Z. Chen, and L. Hood, “Systems medicine: the future of medical genomics and healthcare,” Genome Medicine, vol. 1, no. 1, article 2, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. J. Craig, “Complex diseases: research and applications,” Nature Education, vol. 1, no. 1, p. 184, 2008. View at Google Scholar
  6. C. Ronco, M. Haapio, A. A. House, N. Anavekar, and R. Bellomo, “Cardiorenal syndrome,” Journal of the American College of Cardiology, vol. 52, no. 19, pp. 1527–1539, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. X. Li, X. Xu, J. Wang et al., “A system-level investigation into the mechanisms of chinese traditional medicine: compound danshen formula for cardiovascular disease treatment,” PLoS ONE, vol. 7, no. 9, Article ID e43918, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. P. Jiang, R. Liu, S. Dou et al., “Analysis of the constituents in rat plasma after oral administration of Shexiang Baoxin pill by HPLC-ESI-MS/MS,” Biomedical Chromatography, vol. 23, no. 12, pp. 1333–1343, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. W. Tao, X. Xu, X. Wang et al., “Network pharmacology-based prediction of the active ingredients and potential targets of Chinese herbal Radix Curcumae formula for application to cardiovascular disease,” Journal of Ethnopharmacology, vol. 145, no. 1, pp. 1–10, 2013. View at Publisher · View at Google Scholar · View at Scopus
  10. X. Wang, X. Xu, Y. Li et al., “Systems pharmacology uncovers Janus functions of botanical drugs: activation of host defense system and inhibition of influenza virus replication,” Integrative Biology, vol. 5, no. 2, pp. 351–371, 2013. View at Publisher · View at Google Scholar · View at Scopus
  11. H. Liu, J. Wang, W. Zhou, Y. Wang, and L. Yang, “Systems approaches and polypharmacology for drug discovery from herbal medicines: an example using licorice,” Journal of Ethnopharmacology, vol. 146, no. 3, pp. 773–793, 2013. View at Publisher · View at Google Scholar · View at Scopus
  12. D. K. W. Mok and F.-T. Chau, “Chemical information of Chinese medicines: a challenge to chemist,” Chemometrics and Intelligent Laboratory Systems, vol. 82, no. 1-2, pp. 210–217, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. T. W. Lau, F. F. Y. Lam, K. M. Lau et al., “Pharmacological investigation on the wound healing effects of Radix Rehmanniae in an animal model of diabetic foot ulcer,” Journal of Ethnopharmacology, vol. 123, no. 1, pp. 155–162, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. H. Yu, J. Chen, X. Xu et al., “A systematic prediction of multiple drug-target interactions from chemical, genomic, and pharmacological data,” PLoS ONE, vol. 7, no. 5, Article ID e37608, 2012. View at Publisher · View at Google Scholar · View at Scopus
  15. P. A. Heidenreich, J. G. Trogdon, O. A. Khavjou et al., “Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association,” Circulation, vol. 123, no. 8, pp. 933–944, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. M. V. S. Varma, R. S. Obach, C. Rotter et al., “Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination,” Journal of Medicinal Chemistry, vol. 53, no. 3, pp. 1098–1108, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. X. Xu, W. Zhang, C. Huang et al., “A novel chemometric method for the prediction of human oral bioavailability,” International Journal of Molecular Sciences, vol. 13, no. 6, pp. 6964–6982, 2012. View at Publisher · View at Google Scholar · View at Scopus
  18. P. Geladi and B. R. Kowalski, “Partial least-squares regression: a tutorial,” Analytica Chimica Acta, vol. 185, pp. 1–17, 1986. View at Publisher · View at Google Scholar · View at Scopus
  19. T. Hou and X. Xu, “ADME evaluation in drug discovery,” Molecular Modeling Annual, vol. 8, no. 12, pp. 337–349, 2002. View at Publisher · View at Google Scholar
  20. A. Guerra, N. E. Campillo, and J. A. Páez, “Neural computational prediction of oral drug absorption based on CODES 2D descriptors,” European Journal of Medicinal Chemistry, vol. 45, no. 3, pp. 930–940, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. T. L. Moda and A. D. Andricopulo, “Consensus hologram QSAR modeling for the prediction of human intestinal absorption,” Bioorganic & Medicinal Chemistry Letters, vol. 22, no. 8, pp. 2889–2893, 2012. View at Publisher · View at Google Scholar · View at Scopus
  22. Y. Yao, X. Zhang, Z. Wang et al., “Deciphering the combination principles of Traditional Chinese Medicine from a systems pharmacology perspective based on Ma-huang Decoction,” Journal of Ethnopharmacology, vol. 150, no. 2, pp. 619–638, 2013. View at Publisher · View at Google Scholar · View at Scopus
  23. Y. Yamanishi, M. Kotera, M. Kanehisa, and S. Goto, “Drug-target interaction prediction from chemical, genomic and pharmacological data in an integrated framework,” Bioinformatics, vol. 26, no. 12, Article ID btq176, pp. i246–i254, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. D. S. Wishart, C. Knox, A. C. Guo et al., “DrugBank: a comprehensive resource for in silico drug discovery and exploration,” Nucleic Acids Research, vol. 34, pp. D668–D672, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. L. Li, Y. Li, Y. Wang, and S. Zhang, “Prediction of BBB permeation based on molecular indices,” Chinese Journal of Medicinal Chemistry, vol. 17, no. 4, pp. 221–228, 2007. View at Google Scholar
  26. R. B. Altman, “PharmGKB: a logical home for knowledge relating genotype to drug response phenotype,” Nature Genetics, vol. 39, no. 4, article 426, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. 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 Publisher · View at Google Scholar · View at Scopus
  28. A. P. Davis, C. G. Murphy, R. Johnson et al., “The comparative toxicogenomics database: update 2013,” Nucleic Acids Research, vol. 41, no. 1, pp. D1104–D1114, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. M. E. Smoot, K. Ono, J. Ruscheinski, P.-L. Wang, and T. Ideker, “Cytoscape 2.8: new features for data integration and network visualization,” Bioinformatics, vol. 27, no. 3, Article ID btq675, pp. 431–432, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. C. Huang, C. Zheng, Y. Li, Y. Wang, A. Lu, and L. Yang, “Systems pharmacology in drug discovery and therapeutic insight for herbal medicines,” Briefings in Bioinformatics, vol. 15, no. 5, pp. 710–733, 2014. View at Publisher · View at Google Scholar
  31. G. Bindea, B. Mlecnik, H. Hackl et al., “ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks,” Bioinformatics, vol. 25, no. 8, pp. 1091–1093, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. P. Knekt, J. Kumpulainen, R. Järvinen et al., “Flavonoid intake and risk of chronic diseases,” The American Journal of Clinical Nutrition, vol. 76, no. 3, pp. 560–568, 2002. View at Google Scholar · View at Scopus
  33. S. Egert, A. Bosy-Westphal, J. Seiberl et al., “Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study,” British Journal of Nutrition, vol. 102, no. 7, pp. 1065–1074, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. H.-J. Kwon, Y. B. Ryu, H. J. Jeong et al., “Rhodiosin, an antioxidant flavonol glycoside from Rhodiola rosea,” Journal of the Korean Society for Applied Biological Chemistry, vol. 52, no. 5, pp. 486–492, 2009. View at Publisher · View at Google Scholar
  35. B. J. Willcox, J. D. Curb, and B. L. Rodriguez, “Antioxidants in cardiovascular health and disease: key lessons from epidemiologic studies,” The American Journal of Cardiology, vol. 101, no. 10, pp. S75–S86, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. C. R. Cederroth and S. Nef, “Soy, phytoestrogens and metabolism: a review,” Molecular and Cellular Endocrinology, vol. 304, no. 1-2, pp. 30–42, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. N. I. Krinsky, “Carotenoids as antioxidants,” Nutrition, vol. 17, no. 10, pp. 815–817, 2001. View at Publisher · View at Google Scholar · View at Scopus
  38. Y. Yamamoto and E. Oue, “Antihypertensive effect of quercetin in rats fed with a high-fat high-sucrose diet,” Bioscience, Biotechnology and Biochemistry, vol. 70, no. 4, pp. 933–939, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. I. Mackraj, T. Govender, and S. Ramesar, “The antihypertensive effects of quercetin in a salt-sensitive model of hypertension,” Journal of Cardiovascular Pharmacology, vol. 51, no. 3, pp. 239–245, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. M.-X. Jiang, X.-F. Ruan, and Y. Xu, “Effects of Kanlijian on exercise tolerance, quality of life, and frequency of heart failure aggravation in patients with chronic heart failure,” Chinese Journal of Integrative Medicine, vol. 12, no. 2, pp. 94–100, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. D. L. Tribble, “Further evidence of the cardiovascular benefits of diets enriched in carotenoids,” The American Journal of Clinical Nutrition, vol. 68, no. 3, pp. 521–522, 1998. View at Google Scholar · View at Scopus
  42. H. K. Kim, H. R. Park, J. S. Lee, T. S. Chung, H. Y. Chung, and J. Chung, “Down-regulation of iNOS and TNF-α expression by kaempferol via NF-κB inactivation in aged rat gingival tissues,” Biogerontology, vol. 8, no. 4, pp. 399–408, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. G. L. Firestone and S. N. Sundar, “Anticancer activities of artemisinin and its bioactive derivatives,” Expert Reviews in Molecular Medicine, vol. 11, article e32, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. J. B. Toledo, S. E. Arnold, K. Raible et al., “Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer's Coordinating Centre,” Brain, vol. 136, no. 9, pp. 2697–2706, 2013. View at Publisher · View at Google Scholar · View at Scopus
  45. A. R. Inácio, K. Ruscher, L. Leng, R. Bucala, and T. Deierborg, “Macrophage migration inhibitory factor promotes cell death and aggravates neurologic deficits after experimental stroke,” Journal of Cerebral Blood Flow & Metabolism, vol. 31, no. 4, pp. 1093–1106, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. A. Bierhaus, T. Fleming, S. Stoyanov et al., “Methylglyoxal modification of Na v 1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy,” Nature Medicine, vol. 18, no. 6, pp. 926–933, 2012. View at Publisher · View at Google Scholar · View at Scopus
  47. M. J. Cipolla, Q. Huang, and J. G. Sweet, “Inhibition of protein kinase Cβ reverses increased blood-brain barrier permeability during hyperglycemic stroke and prevents edema formation in vivo,” Stroke, vol. 42, no. 11, pp. 3252–3257, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Mendioroz, I. Fernández-Cadenas, A. Rosell et al., “Osteopontin predicts long-term functional outcome among ischemic stroke patients,” Journal of Neurology, vol. 258, no. 3, pp. 486–493, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. A. Pollak, A. Rokach, A. Blumenfeld, L. J. Rosen, L. Resnik, and R. D. Pollak, “Association of oestrogen receptor alpha gene polymorphism with the angiographic extent of coronary artery disease,” European Heart Journal, vol. 25, no. 3, pp. 240–245, 2004. View at Publisher · View at Google Scholar · View at Scopus
  50. T. A. Kunnas, P. Laippala, A. Penttilä, T. Lehtimäki, and P. J. Karhunen, “Association of polymorphism of human α oestrogen receptor gene with coronary artery disease in men: a necropsy study,” The British Medical Journal, vol. 321, no. 7256, pp. 273–274, 2000. View at Publisher · View at Google Scholar · View at Scopus
  51. K. M. Fischer, C. T. Cottage, M. H. Konstandin, M. Völkers, M. Khan, and M. A. Sussman, “Pim-1 kinase inhibits pathological injury by promoting cardioprotective signaling,” Journal of Molecular and Cellular Cardiology, vol. 51, no. 4, pp. 554–558, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. M. van der Paardt, J. B. A. Crusius, M. A. García-González, B. A. C. Dijkmans, A. S. Peña, and I. E. van der Horst-Bruinsma, “Susceptibility to ankylosing spondylitis: no evidence for the involvement of transforming growth factor β1 (TGFB1) gene polymorphisms,” Annals of the Rheumatic Diseases, vol. 64, no. 4, pp. 616–619, 2005. View at Publisher · View at Google Scholar · View at Scopus
  53. G. Z. Feuerstein, T. Liu, and F. C. Barone, “Cytokines, inflammation, and brain injury: role of tumor necrosis factor-alpha,” Cerebrovascular and Brain Metabolism Reviews, vol. 6, no. 4, pp. 341–360, 1994. View at Google Scholar · View at Scopus
  54. J. C. Braz, K. Gregory, A. Pathak et al., “PKC-α regulates cardiac contractility and propensity toward heart failure,” Nature Medicine, vol. 10, no. 3, pp. 248–254, 2004. View at Publisher · View at Google Scholar · View at Scopus
  55. S. A. Crone, Y.-Y. Zhao, L. Fan et al., “ErbB2 is essential in the prevention of dilated cardiomyopathy,” Nature Medicine, vol. 8, no. 5, pp. 459–465, 2002. View at Publisher · View at Google Scholar · View at Scopus
  56. L. Maier, D. Bers, and J. Brown, “Calmodulin and Ca2+/calmodulin kinases in the heart—physiology and pathophysiology,” Cardiovascular Research, vol. 73, no. 4, pp. 629–630, 2007. View at Publisher · View at Google Scholar
  57. S. Gately and W. W. Li, “Multiple roles of COX-2 in tumor angiogenesis: a target for antiangiogenic therapy,” Seminars in Oncology, vol. 31, no. 7, pp. 2–11, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. T. Murohara and T. Asahara, “Nitric oxide and angiogenesis in cardiovascular disease,” Antioxidants and Redox Signaling, vol. 4, no. 5, pp. 825–831, 2002. View at Publisher · View at Google Scholar · View at Scopus
  59. A. J. Marrogi, W. D. Travis, J. A. Welsh et al., “Nitric oxide synthase, cyclooxygenase 2, and vascular endothelial growth factor in the angiogenesis of non-small cell lung carcinoma,” Clinical Cancer Research, vol. 6, no. 12, pp. 4739–4744, 2000. View at Google Scholar · View at Scopus
  60. R. Aebersold and M. Mann, “Mass spectrometry-based proteomics,” Nature, vol. 422, no. 6928, pp. 198–207, 2003. View at Publisher · View at Google Scholar · View at Scopus
  61. M. S. Joshi, C. Mineo, P. W. Shaul, and J. A. Bauer, “Biochemical consequences of the NOS3 Glu298Asp variation in human endothelium: altered caveolar localization and impaired response to shear,” The FASEB Journal, vol. 21, no. 11, pp. 2655–2663, 2007. View at Publisher · View at Google Scholar · View at Scopus
  62. J.-F. Arnal, A.-T. Dinh-Xuan, M. Pueyo, B. Darblade, and J. Rami, “Endothelium-derived nitric oxide and vascular physiology and pathology,” Cellular and Molecular Life Sciences, vol. 55, no. 8-9, pp. 1078–1087, 1999. View at Publisher · View at Google Scholar · View at Scopus
  63. C. Monaco, N. Terrando, and K. S. Midwood, “Toll-like receptor signaling: common pathways that drive cardiovascular disease and rheumatoid arthritis,” Arthritis Care & Research, vol. 63, no. 4, pp. 500–511, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. D. J. H. McCabe, P. Harrison, I. J. Mackie et al., “Platelet degranulation and monocyte-platelet complex formation are increased in the acute and convalescent phases after ischaemic stroke or transient ischaemic attack,” British Journal of Haematology, vol. 125, no. 6, pp. 777–787, 2004. View at Publisher · View at Google Scholar · View at Scopus
  65. P. A. Cahill and E. M. Redmond, “Alcohol and cardiovascular disease-modulation of vascular cell function,” Nutrients, vol. 4, no. 4, pp. 297–318, 2012. View at Publisher · View at Google Scholar · View at Scopus
  66. L. Ferini-Strambi, A. S. Walters, and D. Sica, “The relationship among restless legs syndrome (Willis–Ekbom Disease), hypertension, cardiovascular disease, and cerebrovascular disease,” Journal of Neurology, vol. 261, no. 6, pp. 1051–1068, 2014. View at Publisher · View at Google Scholar
  67. J.-C. Reil, F. Custodis, K. Swedberg et al., “Heart rate reduction in cardiovascular disease and therapy,” Clinical Research in Cardiology, vol. 100, no. 1, pp. 11–19, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. C. A. Herzog, R. W. Asinger, A. K. Berger et al., “Cardiovascular disease in chronic kidney disease. A clinical update from kidney disease: improving global outcomes (KDIGO),” Kidney International, vol. 80, no. 6, pp. 572–586, 2011. View at Publisher · View at Google Scholar · View at Scopus
  69. R. M. Freedom, F. S. Rosen, and A. S. Nadas, “Congenital cardiovascular disease and anomalies of the third and fourth pharyngeal pouch,” Circulation, vol. 46, no. 1, pp. 165–172, 1972. View at Publisher · View at Google Scholar · View at Scopus
  70. L. Hood and M. Flores, “A personal view on systems medicine and the emergence of proactive P4 medicine: predictive, preventive, personalized and participatory,” New Biotechnology, vol. 29, no. 6, pp. 613–624, 2012. View at Publisher · View at Google Scholar · View at Scopus