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Linked References

1. P. M. Barnes, E. Powell-Griner, K. McFann, and R. L. Nahin, “Complementary and alternative medicine use among adults: United States, 2002,” Advance Data, no. 343, pp. 1–19, 2004. View at Scopus
2. I. A. Khan, “Issues related to botanicals,” Life Sciences, vol. 78, no. 18, pp. 2033–2038, 2006. View at Publisher · View at Google Scholar · View at Scopus
3. N. B. Kumar, K. Allen, and H. Bell, “Perioperative herbal supplement use in cancer patients: potential implications and recommendations for presurgical screening,” Cancer Control, vol. 12, no. 3, pp. 149–157, 2005. View at Scopus
4. B. C. Foster, J. T. Arnason, and C. J. Briggs, “Natural health products and drug disposition,” Annual Review of Pharmacology and Toxicology, vol. 45, pp. 203–226, 2005. View at Publisher · View at Google Scholar · View at Scopus
5. P. M. Wolsko, D. K. Solondz, R. S. Phillips, S. C. Schachter, and D. M. Eisenberg, “Lack of herbal supplement characterization in published randomized controlled trials,” American Journal of Medicine, vol. 118, no. 10, pp. 1087–1093, 2005. View at Publisher · View at Google Scholar · View at Scopus
6. P. M. Coates and C. M. Meyers, “The National Institutes of Health investment in research on botanicals,” Fitoterapia, vol. 82, no. 1, pp. 11–13, 2011. View at Publisher · View at Google Scholar · View at Scopus
7. S. Sasidharan, Y. Chen, D. Saravanan, K. M. Sundram, and L. Yoga Latha, “Extraction, isolation and characterization of bioactive compounds from plants' extracts,” African Journal of Traditional, Complementary and Alternative Medicines, vol. 8, no. 1, pp. 1–10, 2011. View at Scopus
8. G. Speijers, B. Bottex, B. Dusemund et al., “Safety assessment of botanicals and botanical preparations used as ingredients in food supplements: testing an European food safety authority-tiered approach,” Molecular Nutrition and Food Research, vol. 54, no. 2, pp. 175–185, 2010. View at Publisher · View at Google Scholar · View at Scopus
9. A. LeRoy, E. Potter, H. H. Woo, D. Heber, and A. M. Hirsch, “Characterization and identification of alfalfa and red clover dietary supplements using a PCR-based method,” Journal of Agricultural and Food Chemistry, vol. 50, no. 18, pp. 5063–5069, 2002. View at Publisher · View at Google Scholar · View at Scopus
10. Y. L. Yang, W. Y. Liao, W. Y. Liu et al., “Discovery of new natural products by intact-cell mass spectrometry and lc-spe-nmr: malbranpyrroles, novel polyketides from thermophilic fungus malbranchea sulfurea,” Chemistry, vol. 15, no. 43, pp. 11573–11580, 2009. View at Publisher · View at Google Scholar · View at Scopus
11. K. W. Cheng, C. C. Wong, M. Wang, Q. Y. He, and F. Chen, “Identification and characterization of molecular targets of natural products by mass spectrometry,” Mass Spectrometry Reviews, vol. 29, no. 1, pp. 126–155, 2010. View at Publisher · View at Google Scholar · View at Scopus
12. E. Esquenazi, Y. L. Yang, J. Watrous, W. H. Gerwick, and P. C. Dorrestein, “Imaging mass spectrometry of natural products,” Natural Product Reports, vol. 26, no. 12, pp. 1521–1534, 2009. View at Publisher · View at Google Scholar · View at Scopus
13. G. Z. Xin, J. L. Zhou, L. W. Qi, and P. Li, “Mass spectrometry-based strategies for screening of bioactive natural products,” Combinatorial Chemistry and High Throughput Screening, vol. 14, no. 2, pp. 93–103, 2011. View at Publisher · View at Google Scholar · View at Scopus
14. D. Dai, J. He, R. Sun, R. Zhang, H. A. Aisa, and Z. Abliz, “Nuclear magnetic resonance and liquid chromatography-mass spectrometry combined with an incompleted separation strategy for identifying the natural products in crude extract,” Analytica Chimica Acta, vol. 632, no. 2, pp. 221–228, 2009. View at Publisher · View at Google Scholar · View at Scopus
15. Y. Liu, B. Zheng, X. Xu, and G. Yuan, “Probing the binding affinity of small-molecule natural products to the G-quadruplex in C-myc oncogene by electrospray ionization mass spectrometry,” Rapid Communications in Mass Spectrometry, vol. 24, pp. 3072–3075, 2010.
16. L. Nyadong, E. G. Hohenstein, A. Galhena et al., “Reactive desorption electrospray ionization mass spectrometry (DESI-MS) of natural products of a marine alga,” Analytical and Bioanalytical Chemistry, vol. 394, no. 1, pp. 245–254, 2009. View at Publisher · View at Google Scholar · View at Scopus
17. J. Xing, C. Xie, and H. Lou, “Recent applications of liquid chromatography-mass spectrometry in natural products bioanalysis,” Journal of Pharmaceutical and Biomedical Analysis, vol. 44, no. 2, pp. 368–378, 2007. View at Publisher · View at Google Scholar · View at Scopus
18. K. Chobotova, A. B. Vernallis, and F. A. A. Majid, “Bromelain's activity and potential as an anti-cancer agent: current evidence and perspectives,” Cancer Letters, vol. 290, no. 2, pp. 148–156, 2010. View at Publisher · View at Google Scholar · View at Scopus
19. H. R. Maurer, “Bromelain: biochemistry, pharmacology and medical use,” Cellular and Molecular Life Sciences, vol. 58, no. 9, pp. 1234–1245, 2001. View at Scopus
20. A. D. Rowan and D. J. Buttle, “Pineapple cysteine endopeptidases,” Methods in Enzymology, vol. 244, pp. 555–568, 1994. View at Publisher · View at Google Scholar · View at Scopus
21. T. Murachi and H. Neurath, “Fractionation and specificity studies on stem bromelain,” The Journal of Biological Chemistry, vol. 235, pp. 99–107, 1960. View at Scopus
22. S. Ota, E. Muta, Y. Katahira, and Y. Okamoto, “Reinvestigation of fractionation and some properties of the proteolytically active components of stem and fruit bromelains,” Journal of Biochemistry, vol. 98, no. 1, pp. 219–228, 1985. View at Scopus
23. C. W. Wharton, “The structure and mechanism of stem bromelain. Evaluation of the homogeneity of purified stem bromelain, determination of the molecular weight and kinetic analysis of the bromelain catalysed hydrolysis of N benzyloxycarbonyl L phenylalanyl L serine methyl ester,” Biochemical Journal, vol. 143, no. 3, pp. 575–586, 1974. View at Scopus
24. T. Harrach, K. Eckert, H. R. Maurer, I. Machleidt, W. Machleidt, and R. Nuck, “Isolation and characterization of two forms of an acidic bromelain stem proteinase,” Protein Journal, vol. 17, no. 4, pp. 351–361, 1998. View at Scopus
25. T. Harrach, K. Eckert, K. Schulze-Forster, R. Nuck, D. Grunow, and H. R. Maurer, “Isolation and partial characterization of basic proteinases from stem bromelain,” Journal of Protein Chemistry, vol. 14, no. 1, pp. 41–52, 1995. View at Publisher · View at Google Scholar · View at Scopus
26. K. L. Lee, K. L. Albee, R. J. Bernasconi, and T. Edmunds, “Complete amino acid sequence of ananain and a comparison with stem bromelain and other plant cysteine proteases,” Biochemical Journal, vol. 327, no. 1, pp. 199–202, 1997. View at Scopus
27. A. D. Napper, S. P. Bennet, M. Borowski et al., “Purification and characterization of multiple forms of the pineapple-stem-derived cysteine proteinases ananain and comosain,” Biochemical Journal, vol. 301, part 3, pp. 727–735, 1994. View at Scopus
28. A. Ritonja, A. D. Rowan, D. J. Buttle, N. D. Rawlings, V. Turk, and A. J. Barrett, “Stem bromelain: amino acid sequence and implications for weak binding of cystatin,” FEBS Letters, vol. 247, no. 2, pp. 419–424, 1989. View at Scopus
29. F. Yamada, N. Takahashi, and T. Murachi, “Purification and characterization of a proteinase from pineapple fruit, fruit bromelain FA2,” Journal of Biochemistry, vol. 79, no. 6, pp. 1223–1234, 1976. View at Scopus
30. L. P. Hale, “Proteolytic activity and immunogenicity of oral bromelain within the gastrointestinal tract of mice,” International Immunopharmacology, vol. 4, no. 2, pp. 255–264, 2004. View at Publisher · View at Google Scholar · View at Scopus
31. J. V. Castell, G. Friedrich, C. S. Kuhn, and G. E. Poppe, “Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake,” American Journal of Physiology, vol. 273, no. 1, pp. G139–G146, 1997. View at Scopus
32. K. Eckert, E. Grabowska, R. Stange, U. Schneider, K. Eschmann, and H. R. Maurer, “Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients,” Oncology Reports, vol. 6, no. 6, pp. 1191–1199, 1999. View at Scopus
33. L. Desser, D. Holomanova, E. Zavadova, K. Pavelka, T. Mohr, and I. Herbacek, “Oral therapy with proteolytic enzymes decreases excessive TGF-β levels in human blood,” Cancer Chemotherapy and Pharmacology, Supplement, vol. 47, supplement, pp. S10–S15, 2001. View at Scopus
34. G. Klein and W. Kullich, “Short-term treatment of painful osteoarthritis of the knee with oral enzymes. A randomised, double-blind study versus diclofenac,” Clinical Drug Investigation, vol. 19, no. 1, pp. 15–23, 2000. View at Scopus
35. A. Daugsch, C. S. Moraes, P. Fort, and Y. K. Park, “Brazilian red propolis—chemical composition and botanical origin,” Evidence-based Complementary and Alternative Medicine, vol. 5, no. 4, pp. 435–441, 2008. View at Publisher · View at Google Scholar · View at Scopus
36. P. Dugo, F. Cacciola, P. Donato, R. A. Jacques, E. B. Caramão, and L. Mondello, “High efficiency liquid chromatography techniques coupled to mass spectrometry for the characterization of mate extracts,” Journal of Chromatography A, vol. 1216, no. 43, pp. 7213–7221, 2009. View at Publisher · View at Google Scholar · View at Scopus
37. R. Tilton, A. A. Paiva, J. Q. Guan et al., “A comprehensive platform for quality control of botanical drugs (PhytomicsQC): a case study of Huangqin Tang (HQT) and PHY906,” Chinese Medicine, vol. 5, article 30, 2010. View at Publisher · View at Google Scholar · View at Scopus
38. E. Munzig, “Bromelain protease F9 reduces the CD44 mediated adhesion of human peripheral blood lymphocytes to human umbilical vein endothelial cells,” FEBS Letters, vol. 351, no. 2, pp. 215–218, 1994. View at Publisher · View at Google Scholar · View at Scopus
39. E. R. Secor Jr., W. F. Carson, M. M. Cloutier et al., “Bromelain exerts anti-inflammatory effects in an ovalbumin-induced murine model of allergic airway disease,” Cellular Immunology, vol. 237, no. 1, pp. 68–75, 2005. View at Publisher · View at Google Scholar · View at Scopus
40. E. R. Secor Jr., A. Singh, L. A. Guernsey et al., “Bromelain treatment reduces CD25 expression on activated CD4⁺ T cells in vitro,” International Immunopharmacology, vol. 9, no. 3, pp. 340–346, 2009. View at Publisher · View at Google Scholar · View at Scopus
41. V. Mayya, K. Rezual, L. Wu, M. B. Fong, and D. K. Han, “Absolute quantification of multisite phosphorylation by selective reaction monitoring mass spectrometry,” Molecular and Cellular Proteomics, vol. 5, no. 6, pp. 1146–1157, 2006. View at Publisher · View at Google Scholar · View at Scopus
42. C. Bagnato, J. Thumar, V. Mayya et al., “Proteomics analysis of human coronary atherosclerotic plaque: a feasibility study of direct tissue proteomics by liquid chromatography and tandem mass spectrometry,” Molecular and Cellular Proteomics, vol. 6, no. 6, pp. 1088–1102, 2007. View at Publisher · View at Google Scholar · View at Scopus
43. L. Wu, S. I. Hwang, K. Rezaul et al., “Global survey of human T leukemic cells by integrating proteomics and transcriptomics profiling,” Molecular and Cellular Proteomics, vol. 6, no. 8, pp. 1343–1353, 2007. View at Publisher · View at Google Scholar · View at Scopus
44. K. Rezaul, L. Wu, V. Mayya, S. I. Hwang, and D. Han, “A systematic characterization of mitochondrial proteome from human T leukemia cells,” Molecular and Cellular Proteomics, vol. 4, no. 2, pp. 169–181, 2005. View at Publisher · View at Google Scholar · View at Scopus
45. J. Hoback, NFM Market Overview 2011, Natural Products Stores sales up 7 Percent in 2010, Natural Foods Merchandiser, 2011.
46. T. Neely, B. Walsh-Mason, P. Russell, A. V. Horst, S. O'Hagan, and P. Lahorkar, “A multi-criteria decision analysis model to assess the safety of botanicals utilizing data on history of use,” Toxicology International, vol. 18, supplement 1, pp. S20–S29, 2011.
47. T. J. Smillie and I. A. Khan, “A comprehensive approach to identifying and authenticating botanical products,” Clinical Pharmacology and Therapeutics, vol. 87, no. 2, pp. 175–186, 2010. View at Publisher · View at Google Scholar · View at Scopus
48. L. P. Hale, K. H. Singer, and B. F. Haynes, “CD44 antibody against In(Lu)-related p80, lymphocyte-homing receptor molecule inhibits the binding of human erythrocytes to T cells,” Journal of Immunology, vol. 143, no. 12, pp. 3944–3948, 1989. View at Scopus
49. “Bromelain monograph,” Alternative Medicine Reviewm, vol. 15, no. 4, pp. 361–368, 2011.
50. A. Dickinson, “History and overview of DSHEA,” Fitoterapia, vol. 82, no. 1, pp. 5–10, 2011. View at Publisher · View at Google Scholar · View at Scopus
51. J. Hildreth, E. Hrabeta-Robinson, W. Applequist, J. Betz, and J. Miller, “Standard operating procedure for the collection and preparation of voucher plant specimens for use in the nutraceutical industry,” Analytical and Bioanalytical Chemistry, vol. 389, no. 1, pp. 13–17, 2007. View at Publisher · View at Google Scholar · View at Scopus
52. M. E. Gershwin, A. T. Borchers, C. L. Keen, S. Hendler, F. Hagie, and M. R. C. Greenwood, “Public safety and dietary supplementation,” Annals of the New York Academy of Sciences, vol. 1190, pp. 104–117, 2010. View at Publisher · View at Google Scholar · View at Scopus
53. R. Giunta, G. Basile, and A. Tibuzzi, “Legislation on nutraceuticals and food supplements: a comparison between regulations in USA and EU,” Advances in Experimental Medicine and Biology, vol. 698, pp. 322–328, 2010. View at Publisher · View at Google Scholar · View at Scopus
54. G. Speijers, B. Bottex, B. Dusemund et al., “Safety assessment of botanicals and botanical preparations used as ingredients in food supplements: testing an European food safety authority-tiered approach,” Molecular Nutrition and Food Research, vol. 54, no. 2, pp. 175–185, 2010. View at Publisher · View at Google Scholar · View at Scopus
55. Y. Sawano, T. Muramatsu, K. I. Hatano, K. Nagata, and M. Tanokura, “Characterization of genomic sequence coding for bromelain inhibitors in pineapple and expression of its recombinant isoform,” Journal of Biological Chemistry, vol. 277, no. 31, pp. 28222–28227, 2002. View at Publisher · View at Google Scholar · View at Scopus
56. S. Szilágyi and E. Szilágyi, “Apparent sequence homology among leguminosae small molecular weight, cystine rich protease inhibitors and pineapple stem bromelain inhibitors,” Acta Biochimica et Biophysica, vol. 13, no. 4, pp. 293–298, 1978. View at Scopus
57. T. L. R. Mynott, C. Engwerda, and P. Keith, “Component of bromelain,” Edited by United States, T. L.Mynott, 2004.
58. A. D. Rowan, D. J. Buttle, and A. J. Barrett, “The cysteine proteinases of the pineapple plant,” Biochemical Journal, vol. 266, no. 3, pp. 869–875, 1990. View at Scopus
59. E. M. Skrabut, P. A. Hebda, J. A. Samuels et al., “Removal of necrotic tissue with an ananain-based enzyme-debriding preparation,” Wound Repair and Regeneration, vol. 4, no. 4, pp. 433–443, 1996. View at Scopus
60. S. Raval, S. B. Gowda, D. D. Singh, and N. R. Chandra, “A database analysis of jacalin-like lectins: sequence-structure-function relationships,” Glycobiology, vol. 14, no. 12, pp. 1247–1263, 2004. View at Publisher · View at Google Scholar · View at Scopus
61. Q. H. Ma, B. Tian, and Y. L. Li, “Overexpression of a wheat jasmonate-regulated lectin increases pathogen resistance,” Biochimie, vol. 92, no. 2, pp. 187–193, 2010. View at Publisher · View at Google Scholar · View at Scopus
62. S. Kabir, “Jacalin: a jackfruit (Artocarpus heterophyllus) seed-derived lectin of versatile applications in immunobiological research,” Journal of Immunological Methods, vol. 212, no. 2, pp. 193–211, 1998. View at Publisher · View at Google Scholar · View at Scopus
63. R. R. White, F. E. H. Crawley, M. Vellini, and L. A. Rovati, “Bioavailability of 125I bromelain after oral administration to rats,” Biopharmaceutics and Drug Disposition, vol. 9, no. 4, pp. 397–403, 1988. View at Scopus
64. J. Seifert, R. Ganser, and W. Brendel, “Absorption of a proteolytic enzyme originating from plants out of the gastro-intestinal tract into blood and lymph of rats,” Zeitschrift fur Gastroenterologie, vol. 17, no. 1, pp. 1–8, 1979. View at Scopus
65. R. Willoughby ES and S. Mitrovich, A Global View of LC/MS, Global View, 1988.
66. D. M. Ribnicky, A. Poulev, B. Schmidt, W. T. Cefalu, and I. Raskin, “Evaluation of botanicals for improving human health,” American Journal of Clinical Nutrition, vol. 87, no. 2, pp. 472S–475S, 2008. View at Scopus
67. P. Ninfali, L. Gennari, E. Biagiotti, F. Cangi, L. Mattoli, and A. Maidecchi, “Improvement in botanical standardization of commercial freeze-dried herbal extracts by using the combination of antioxidant capacity and constituent marker concentrations,” Journal of AOAC International, vol. 92, no. 3, pp. 797–805, 2009. View at Scopus
68. A. Ibarra, J. Cases, A. Bily et al., “Importance of extract standardization and in vitro/ex vivo assay selection for the evaluation of antioxidant activity of Botanicals: a case study on three rosmarinus officinalis L. extracts,” Journal of Medicinal Food, vol. 13, no. 5, pp. 1167–1175, 2010. View at Publisher · View at Google Scholar · View at Scopus