Antimicrobial, antiviral and immunomodulatory activity studies of pelargonium sidoides (EPs® 7630) in the context of health promotion

Pharmaceuticals

Volumn 4, Issue 10, 2011, Pages 1295-1314

  Kolodziej, Herbert ^a  

^a FREIE UNIVERSITÄT BERLIN   (Germany)

Author keywords

Antibacterial; Antiviral; Immunomodulation; Pelargonium sidoides

Indexed keywords

CELL SURFACE MARKER; GAMMA INTERFERON; GAMMA INTERFERON RECEPTOR 1; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 12; MESSENGER RNA; NITRIC OXIDE; PELARGONIUM SIDOIDES EXTRACT; POLYPEPTIDE ANTIBIOTIC AGENT; STIBOGLUCONATE SODIUM; TUMOR NECROSIS FACTOR ALPHA; UMCKALOABO; ZANAMIVIR;

ANTIVIRAL ACTIVITY; BACTERIUM ADHERENCE; BRONCHITIS; CYTOKINE RELEASE; DISEASE ASSOCIATION; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG SCREENING; GENE EXPRESSION REGULATION; HEALTH PROMOTION; HERPES SIMPLEX VIRUS 1; HERPES SIMPLEX VIRUS 2; HOST RESISTANCE; HUMAN; IC 50; IMMUNOMODULATION; IN VITRO STUDY; INNATE IMMUNITY; INTRACELLULAR KILLING; LEISHMANIASIS; LOW DRUG DOSE; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PHAGOCYTOSIS; PHYTOCHEMISTRY; PROTEIN FUNCTION; RESPIRATORY TRACT INFECTION; REVIEW; SINUSITIS; STAPHYLOCOCCUS AUREUS; STREPTOCOCCUS PNEUMONIAE; TONSILLITIS; TRADITIONAL MEDICINE; TUBERCULOSIS; UPREGULATION;

EID: 80055089662     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph4101295     Document Type: Review

References (81)

1. WHO. Health statistics and health information systems. Available online: http://www.who.int/healthinfo/statistics (accessed on 22 June 2011).
2. Watt, J.M.; Breyer-Brandwyk, M.G. Medicinal and Poisonous Plants of Southern and Eastern Africa; Livingstone: Edinburgh/London, UK, 1962; pp. 449-455.
3. Hutchings A. Zulu Medicinal Plants; Natal University Press: Pietermaritzburg, South Africa, 1996.
4. ® 7630. Phytomedicine 2007, 14, 18-26.
5. Brendler, T.; van Wyk, B.E. A historical, scientific and commercial perspective on the medicinal use of Pelargonium sidoides (Geraniaceae). J. Ethnopharmacol. 2008, 119, 420-433.
6. Helmstädter, A. Umckaloabo - Late vindication of a secret remedy. Pharm. Historian 1996, 26, 2-4.
7. Taylor, P.W.; Maalim, S.; Coleman, S. The strange story of Umckaloabo. Pharmac. J. 2005, 275, 790-792.
8. Kolodziej, H. Aqueous ethanolic extract of the roots of Pelargonium sidoides - New scientific evidence for an old anti-infective phytopharmaceutica. Planta Med. 2008, 74, 661-666.
9. ®. Phytomedicine 2007, 14, 9-17.
10. ® 7630): A randomized, double-blind, placebo-controlled trial. Explore 2005, 1, 437-445.
11. ® 7630-solution in acute bronchitis in childhood: Report of a multicentre observational study. Phytomedicine 2007, 14, 60-64.
12. ® 7630): A randomised, double-blind, placebo-controlled multicentre study. Curr. Med. Res. Opin. 2007, 23, 323-331.
13. Lizogub, V.G.; Riley, D.S.; Heger, M. Efficacy of a Pelargonium sidoides preparation in patients with the common cold: A randomized, double blind, placebo-controlled clinical trial. Explore 2007, 3, 573-584.
14. ® 7630 improves acute bronchitis symptoms and shortens time to remission. Results of a randomized, double-blind, placebo-controlled, multicentre trial. Planta Med. 2008, 7, 686-692.
15. Agbabiaka, T.B.; Guo, R.; Ernst, E. Pelargonium sidoides for acute bronchitis: A systematic review and meta-analysis. Phytomedicine 2008, 15, 378-385.
16. Bachert, C.; Schapowal, A.; Funk, P.; Kieser, M. Treatment of acute rhinosinusitis with the preparation from Pelargonium sidoides EPs 7630: A randomized, double-blind, placebo-controlled trial. Rhinology 2009, 47, 51-55.
17. Kamin W.; Maydannik, V.G.; Malek, F.A.; Kieser, M. Efficacy and tolerability of EPs 7630 in children and adolescents with acute bronchitis: A randomized, double-blind, placebo-controlled multicenter trial with a herbal drug preparation from Pelargonium sidoides roots. Int. J. Clin. Pharmacol. Ther. 2010, 48, 184-191.
18. Kirk, K.M.; Garbes Netto, P.G. Post-marketing surveillance of Pelargonium sidoides for treatment of presumably viral acute community acquired tonsillopharyngitis. Rev. Panam. Infectol. 2007, 9, 15-24.
19. Gonzales, R.; Sande, A.M. Uncomplicated acute bronchitis. Ann. Intern. Med. 2000, 133, 981-991.
20. Gonzales, R.; Bartlett, J.G.; Besser, R.E.; Cooper, R.J.; Hickner, J.M.; Hoffmann, J.R.; Sande, A.M. Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: Background. Ann. Emerg. Med. 2001, 37, 720-727.
21. Gödecke, T. Phytochemische und Pharmakologische Untersuchungen an Pelargonium sidoides DC. PhD. Thesis, Freie Universität Berlin: Berlin, Germany, 2005.
22. Taylor, P.W. Antimycobacterial activity of indigenous South African plants. S. Afr. Med. J. 2003, 93, 904-907.
23. Seidel, V.; Taylor, P.W. In vitro activity of extracts and constituents of Pelargonium against rapidly growing mycobacteria. Int. J. Antimicrob. Agents 2004, 23, 613-619.
24. Mativandlela, S.N.P.; Lall, N.; Meyer, J.J.M. Antibacterial, antifungal and antitubercular activity of Pelargonium reniforme Curtis and Pelargonium sidoides DC. (Geraniaceae) root extracts. S. Afr. J. Bot. 2006, 72, 232-237.
25. Mativandlela, S.N.P.; Meyer, J.J.M.; Hussein, A.A.; Lall, N. Antitubercular activity of compounds isolated from Pelargonium sidoides. Pharm. Biol. 2007, 45, 645-650.
26. Kayser, O.; Kolodziej, H. Antibacterial activity of extracts and constituents of Pelargonium sidoides and Pelargonium reniforme. Planta Med. 1997, 63, 508-510.
27. Uslu, H.; Yoruk, O.; Ayyildiz, A.; Aktan, B. Antibacterial spectrum of Umckaloabo (Pelargonium sidoides) on upper airway infection agents. Eur. J. Gen. Med. 2009, 6, 245-248.
28. ® 7630) inhibits the interactions of group A-streptococci and host epithelia in vivo. Phytomedicine 2007, 14, 52-59.
29. ® 7630) for its activity against group A-streptococci adhesion to human HEp-2 cells. J. Ethnopharmacol. 2011, 133, 147-152.
30. Podbielski, A.; Kreikemeyer, B. The background of tissue specificity of Streptococcus pyogenes. Bioforum 2009, 29, 32-34
31. ® 7630, an extract from Pelargonium sidoides roots inhibits adherence of Helicobacter pylori to gastric epithelial cells. Phytomedicine 2007, 14, 5-8.
32. ® 7630) inhibits in situ adhesion of Helicobacter pylori to human stomach. Phytomedicine 2007, 14, 285-288.
33. Neugebauer, P.; Mickenhagen, A.; Siefer, O.; Walger, M. A new approach to pharmacological effects on ciliary beat frequency in cell cultures - Exemplary measurements under Pelargonium sidoides extract. Phytomedicine 2005, 12, 47-52.
34. Marcucci, F.; Klein, B.; Kirchner, M.; Zawatzky, R. Production of high titers of interferon gamma by prestimulated spleen cells. Eur. J. Immunol. 1982, 12, 787-790.
35. Kolodziej, H.; Kayser, O.; Radtke, O.A.; Kiderlen, A.F.; Koch, E. Pharmacological profile of extracts of Pelargonium sidoides and their constituents. Phytomedicine 2003, 10, 18-24.
36. ® 7630): Effects of induced NO-production on Leismania major in infected macrophages and antiviral effects as assessed in a fibroblast-virus protection assay. Planta Med 2011, 77, 718-725.
37. Schroder, K.; Hertzog, P.J.; Ravani, T.; Hume, D.A. Interferon-γ: An overview of signals, mechanisms and functions. J. Leukoc. Biol. 2004, 75, 163-189.
38. Pestka, S.; Krause, C.D.; Walter, M.R. Interferons, interferon-like cytokines and their receptors. Immunol. Rev. 2004, 202, 8-32.
39. Ank, N.; Iversen, M.B.; Bartholdy, C.; Staeheli, P.; Hartmann, R.; Jensen, U.B.; Dagnaes-Hansen, F.; Thomsen, A.R.; Chen, Z.; Haugen, H.; et al. An important role for type III interferon (IFN-lamba/IL-2) in TLR-induced antiviral activity. J. Immunol. 2008, 180, 2474-2485.
40. ® 7630. Planta Med. 2010, 76, 1291.
41. Kolodziej, H.; Kayser, O.; Kiderlen, A.F.; Ito, H.; Hatano, T.; Yoshida, T.; Foo, L.Y. Proanthocyanidins and related compounds: Antileishmanial activity and modulatory effects on nitric oxide and tumour necrosis factor α release in the murine macrophage-like cell line RAW 264.7. Biol. Pharm. Bull. 2001, 24, 1016-1021.
42. Biron, C.A. Interferons α and ß as immune regulators - A new look. Immunity 2001, 41, 661-664.
43. Schnitzler, P.; Schneider, S.; Stintzing, F.C.; Carle, R.; Reichling, J. Efficacy of an aqueous Pelargonium sidoides extract against herpesvirus. Phytomedicine 2008, 15, 1108-1116.
44. ® 7630, a herbal drug preparation from Pelargonium sidoides, on replication of a broad panel of respiratory viruses. Phytomedicine 2011, 18, 384-386.
45. von Itzstein, M. The war against influenza: Discovery and development of sialidase inhibitors. Nat. Rev. Drug Discov. 2007, 6, 967-974.
46. Potier, M.; Mameli, L.; Belisle, M.; Dallaire, L.; Melancon, S.B. Fluorometric assay of neuraminidase with a sodium (4-methylumbelliferyl-α-D-N-acetylneuraminate) substrate. Anal. Biochem. 1979, 94, 287-296.
47. ® 7630 for its ability to inhibit neuraminidase using sodium (4-methyl-umbelliferyl)-α-D-N-acetylneuraminate as substrate. Planta Med. 2009, 75, 989.
48. Muller, C.P. Institute of Immunology, Centre de Recherche Public-Santé/Laboratoire National de Santè, Luxembourg. Personal communication, 2011.
49. Moncada, S.; Palmer, R.M.J.; Higgs, E.A. Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 1991, 43, 109-142.
50. Nathan, C.F.; Hibbs, J. Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr. Opin. Immunol. 1991, 3, 65-70.
51. Liew, F.Y.; Wei, X.Q.; Proudfoot, L. Cytokines and nitric oxide as effector molecules against parasitic infections. Phil. Trans. Royal Soc. Lond. B 1997, 352, 1311-1315.
52. Bogdan, C.; Röllinghoff, M.; Diefenbach, A. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Curr. Opin. Immunol. 2000, 12, 64-76.
53. Bredt, D.S. Endogeneous nitric oxide synthesis: Biological functions and pathophysiology. Free Radic. Res. 1999, 31, 577-596.
54. Reiner, S.L.; Locksley, R.M. The regulation of immunity to Leishmania major. Annu. Rev. Immunol. 1995, 13, 151-177.
55. r congenic mouse strains. Infect. Immun. 1991, 59, 3935-3944.
56. Deng, W.; Thiel, B.; Tannenbau, C.S.; Hamilton, T.A.; Stuehr, D.J. Synergistic cooperation between T cell lymphokines for induction of the nitric oxide synthase gene in murine peritoneal macrophages. J. Immunol. 1993, 151, 322-329.
57. Ding, A.H.; Nathan, C.F.; Stuehr, D.J. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J. Immunol. 1988, 141, 2407-2412.
58. Ernst, J.D. Macrophage receptors for Mycobacterium tuberculosis. Infect. Immun. 1998, 66, 1277-1281.
59. ® 7630) improves phagocytosis, oxidative burst, and intracellular killing of human peripheral blood phagocytes in vitro. Phytomedicine 2007, 14, 46-51.
60. Kayser, O.; Kolodziej, H.; Kiderlen, A.F. Immunomodulatory principles of Pelargonium sidoides. Phytother. Res. 2001, 15, 122-126.
61. Kiderlen, A.F.; Kaye, P.M. A modified colorimetric assay of macrophage activation for intracellular cytotoxicity against Leishmania parasites. J. Immunol. Methods 1990, 127, 11-18.
62. Kram, D.; Thäle, C.; Kolodziej, H.; Kiderlen, A.F. Intracellular parasite kill: Flow cytometry and NO detection for rapid discrimination between anti-leishmanial activity and macrophage activation. J. Immunol. Methods 2008, 333, 79-88.
63. Kiderlen, A.F.; Kayser, O.; Ferreira, D.; Kolodziej, H. Tannins and related compounds: Killing of amastigotes of Leishmania donovani and release of nitric oxide and tumour necrosis factor α in macrophages in vitro. Z. Naturforsch. 2001, 56c, 444-454.
64. ® 7630 at the molecular level. Planta Med. 2008, 74, 675-681.
65. North, R.J.; Dunn, P.L.; Conlan, J.W. Murine listeriosis as a model for antimicrobial defense. Immunol. Rev. 1997, 158, 27-36.
66. Wagner, H.; Jurcic, K. Methods in Plant Biochemistry; Dey, P.M., Harborne, J.B., Eds.; Academic Press: London, UK, 1991; volume 6, pp. 195-217.
67. Radtke, O.A.; Kiderlen, A.F.; Kayser, O.; Kolodziej, H. Gene expression profiles of inducible nitric oxide synthase and cytokines in Leishmania major-infected macrophage-like RAW 264.7 cells treated with gallic acid. Planta Med. 2004, 70, 924-928.
68. Kolodziej, H.; Burmeister, A.; Trun, W.; Radtke, O.A.; Kiderlen, A.F.; Ito, H.; Hatano, T.; Yoshida, T.; Foo, L.Y. Tannins and related compounds induce nitric oxide synthase and cytokines gene expressions in Leishmania major-infected macrophage-like RAW 264.7 cells. Bioorg. Med. Chem. 2005, 13, 6470-6476.
69. ® 7630). Phytomedicine 2006, 13, 570-575.
70. Mocellin, S.; Panelli, M.C.; Wang, E.; Nagorsen, D.; Marincola, F.M. The dual role of IL-10. Trends Immunol. 2003, 24, 36-38
71. Mogensen, S.C.; Virelizier, J.L. The interferon-macrophage alliance. Interferon 1987, 8, 55-84.
72. Gessani, S.; Belardelli, F. IFN-γ expression in macrophages and its possible biological significance. Cytokine Growth Factor Rev. 1998, 9, 117-123.
73. Trinchieri, G. Interleukin-12: A proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen specific adaptive immunity. Annu. Rev. Immunol. 1995, 13, 251-276.
74. Sugawara, I. Interleukin-18 (IL-18) and infectious diseases, with special emphasis on diseases induced by intracellular pathogens. Microbes Infect. 2000, 2, 1257-1263.
75. Kolodziej, H.; Kiderlen, A.F. Antileishmanial activity and immune modulatory effects of tannins and related compounds on Leishmania parasitised RAW 264.7 cells. Phytochemistry 2005, 66, 2056-2071.
76. Andrade, R.M.; Portillo, J.A.; Wessendarp, M.; Subauste, C.S. CD40 signalling in macrophages induces activity against an intracellular pathogen independently of gamma interferon and reactive nitrogen intermediates. Infect. Immun. 2005, 73, 3115-3123.
77. Andrade, R.M.; Wessendar, M.; Subauste, C.S. CD154 activates macrophage antimicrobial activity in the absence of IFN-gamma through a TNF-alpha-dependent mechanism. J. Immunol. 2003, 171, 6750-6756.
78. van Kooten, C.; Banchereau, J. CD40-CD40 ligand. J. Leukoc. Biol. 2000, 67, 2-17.
79. Demuth, A.; Goebel, W.; Beuscher, H.U.; Kuhn, M. Differential regulation of cytokine and cytokine receptor mRNA expression upon infection of bone marrow-derived macrophages with Listeria monocytogenes. Infect. Immun. 1996, 64, 3475-3483.
80. Tau, G.; Rothman, P. Biologic functions of the IFN-gamma receptors. Allergy 1999, 54, 1233-1251.
81. ® 7630 stimulates release of antimicrobial peptides from neutrophil granulocytes in human whole blood. Planta Med. 2007, 73, doi: 10.1055/s-2007-986854.