Skip to main content
SpringerLink
Log in

An In Vitro Investigation of the Anti-Inflammatory Properties of Potassium Humate

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

In this study the anti-inflammatory potential of potassium humate, derived from bituminous coal, has been investigated in vitro. Exposure of resting and phorbol-12-myristate-13-acetate (PMA) stimulated human neutrophils to potassium humate resulted in a decreased expression of CR3 by activated, but not resting cells, in a dose-related way. Humate also inhibited the adhesion of PMA-stimulated neutrophils to a baby hamster kidney cell line expressing ICAM1 (the CR3 ligand) (BHK331-7). Similar results were obtained using normal BHK cells indicating that this inhibition does not only target specific adhesion molecules on the neutrophil and eosinophil membrane by activated phagocytes, but also affects other mechanisms involved in cell adhesion. Opsonised Sephadex or FMLP/Cyto B-induced degranulation of neutrophils and eosinophils were also decreased by humate treatment. Inhibition of the adhesion of activated phagocytes, as well as inhibition of the release of granule polypeptides, both of which are responsible for tissue damage during inflammatory processes, are attractive targets for anti-inflammatory drugs. Because humate is well tolerated with an excellent safety profile it merits further evaluation in patients suffering from inflammatory conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Hartenstein, R. 1981. Sludge decomposition and stabilization. Science 212:743-749.

    Google Scholar 

  2. Visser, S. A. 1973. Some biological effects of humic acids in the rat. Acta. Biol. Med. Germ. 31:569-581.

    PubMed  Google Scholar 

  3. Baatz, H. 1988. Moortherapie en der Frauenheilkunde. In: Moortherapie: Grundlagen und Anwendungen, W. Flaig, C. Goecke, and W. Kauffels, eds. Ueberreuter, Wien-Berlin, pp. 161-168.

    Google Scholar 

  4. Kleinschmidt, J. 1988. Moortherapie bei rheumatischen Erkrankungen. In: Moortherapie: Grundlagen und Anwendungen, W. Flaig, C. Goecke, and W. Kauffels, eds. Ueberreuter, Wien-Berlin, pp. 216-224.

    Google Scholar 

  5. Kovarik, R. 1988. Über die Anwendung von Präparaten aus Torf, bzw. Huminstoffen bei gynäkologischen Erkrankungen. In: Moortherapie: Grundlagen und Anwendungen, W. Flaig, C. Goecke, and W. Kauffels, eds. Ueberreuter, Wien-Berlin, pp. 177-197.

    Google Scholar 

  6. Lent, W. 1988. Bericht über die Moorforschung und anwendung in der DDR, Polen, Tschechoslowakei und UdSSR. In: Moortherapie: Grundlagen und Anwendungen, W. Flaig, C. Goecke, and W. Kauffels eds. Ueberreuter, Wien-Berlin, pp. 169-176.

    Google Scholar 

  7. Goel, R. K., R. S. Banerjee, and S. B. Acharya. 1990. Antiulcerogenic and antiinflammatory studies with Shilajit. J. Ethnopharmacol. 29:95-103.

    Article  PubMed  Google Scholar 

  8. Schepetkin, I., A. Khlebnikov, and B. S. Kwon. 2002. Medical drugs from humus matter: Focus on Mumie. Drug Dev. Res. 57:140-159.

    Article  Google Scholar 

  9. Soliev, T. S. 1983. The treatment of deforming osteoarthrosis by non-specific bio-stimulator Mumie. Med. J. Uzbek 8:19-21.

    Google Scholar 

  10. Cloete, T. E., H. Swart, I. J. Cronje, and J. Dekker. 1990. Oxidized coal products as industrial bactericides. In: Third International Symposium on Gas, Oil, Coal and Environmental Biotechnology, New Orleans, Louisiana, December 3-5.

  11. van Rensburg, C. E. J., A. van Straten, and J. Dekker. 2000. An in vitro investigation of the antimicrobial activity of oxifulvic acid. J. Antimicrob. Chemother. 46:853-854.

    Article  PubMed  Google Scholar 

  12. van Rensburg, C. E. J., S. C. K. Malfeld, and J. Dekker. 2002. Topical application of oxifulvic acid suppresses the cutaneous immune response in mice. Chemotherapy 48:138-143.

    Article  PubMed  Google Scholar 

  13. Snyman, J. R., J. Dekker, S. C. K. Malfeld, and C. E. J. van Rensburg. 2002. A pilot study to evaluate the safety and therapeutic efficacy of topical oxifulvic acid in atopic volunteers. Drug Dev. Res. 57:40-43.

    Article  Google Scholar 

  14. Jooné, G. K., J. Dekker, and C. E. J. van Rensburg. 2003. Investigation of the immunostimulatory properties of oxihumate. Z. Naturforsch. Redaktion. 58:263-267.

    Google Scholar 

  15. Bansal, V. S., S. Vaidya, E. P. Somers, M. Kanuga, D. Shevell, R. Weikel, and P. A. Detmers. 2003. Small molecule antagonists of complement receptor type 3 block adhesion and adhesion-independent oxidative burst in human polymorphonuclear leukocytes. J. Pharmacol. Exp. Ther. 1016-1024.

  16. Håkanson, L., M. D. Björnsson, C. Janson, and M. D. Schmekel. 1995. Increased adhesion to vascular cell adhesion molecule-1 of eosinophls from patients with asthma. J. Allergy Clin. Immunol. 96:941-950.

    PubMed  Google Scholar 

  17. Ballesteros, J. F., M. J. Sanz, A. Ubeda, M. A. Miranda, S. Iborra, M. Paya, and M. J. Alcaraz. 1995. Synthesis and pharmacological evaluation of 2′-hydroxychalcones and flavones as inhibitors of inflammatory mediators generation. J. Med. Chem. 38:2794-2797.

    PubMed  Google Scholar 

  18. Blackburn, W. D., Jr., L. W. Heck, L. D. Loose, J. D. Eskra, and T. J. Carty. 1991. Inhibition of 5-lipoxygenase product formation and polymorphonuclear cell degranulation by tenidap sodium in patients with rheumatoid arthritis. Arthritis Rheum. 34:204-210.

    PubMed  Google Scholar 

  19. Spisani, S. S. Traniello, A. M. Onori, C. Martuccio, and L. Cellai. 1998. 3-(Carboxalkylthio) rifamycin S and SV derivatives inhibit human neutrophil functions. Inflammation 22:459-469.

    Article  PubMed  Google Scholar 

  20. Bergh, J. J., I. J. Cronje, J. Dekker, T. G. Dekker, L. M. Gerritsma, and L. J. Mienie. 1997. Non-catalytic oxidation of water-slurried coal with oxygen: Identification of fulvic acids and acute toxicity. Fuel 76:149-154.

    Article  Google Scholar 

  21. Piccolo, A., P. Conte, and A. Cozzolino. 2000. Differences in high performance size exclusion chromatography between humic substances and macromolecular polymers. In: Humic Substances: Versatile Components of Plants, Soils and Water, E. A. Ghabbour and G. Davies, eds. Royal Society of Chemistry, Cambridge, UK, pp. 111-124.

    Google Scholar 

  22. Håkanson, L., L. S. Nielson, and P. Teder. 1994. Measurement of neutrophil and eosinophil adhesion to E-selectin, VCAM-1 and ICAM-1 by the use of transfected fibroblast cell lines. J. Immunol. Methods 176:53-66.

    Article  PubMed  Google Scholar 

  23. Böyum, A. 1968. Isolation of leucocytes from human blood. Further observations: Methylcellulose, dextran, and ficoll as erythrocyte aggregating agents. Scand. J. Clin. Lab. Invest. 21:31-50.

    Google Scholar 

  24. Ras, G. J., R. Anderson, G.W. Taylor, J. E. Savage, E. van Niekerk, G. Joone, H. J. Koornhof, J. Saunders, R. Wilson, and P. J. Cole. 1992. Clindamycin, erythromycin, and roxithromycin inhibit the proinflammatory interactions of Pseudomonas aeruginosapigments with human neutrophils in vitro. Antimicrob. Agents Chemother. 36(6):1236-1240.

    PubMed  Google Scholar 

  25. Weiss, S. J. 1989. Tissue destruction by neutrophils. N. Engl. J. Med. 320:365-376.

    PubMed  Google Scholar 

  26. Jaeschke, H., A. Farhood, A. P. Bautista, Z. Spolarics, J. J. Spitzer, and C. W. Smith. 1993. Functional inactivation of neutrophils with Mac-1 (CD11b/CD18) monoclonal antibody protects against ischemia-reperfusion injury in rat liver. Hepatology 17:915-923.

    Article  PubMed  Google Scholar 

  27. Jaeschke, H., A. Farhood, and C. W. Smith. 1991. Neutrophil induced liver cell injury in endotoxin shock is a CD11b/CD18-dependant mechanism. Am. J. Physiol. 261:G1051-G1056.

    PubMed  Google Scholar 

  28. Burch, R. M., M. Weitzberg, L. Noronha-Blob, V. C. Lowe, J. M. Bator, J. Perumattam, and J. P. Sullivan. 1992. Leumedins. Drug News Prospect. 5:331-337.

    Google Scholar 

  29. Stadnyk, A. W., D. Dollard, T. B. Issekutz, and A. C. Issekutz. 2002. Neutrophil migration into indomethacin induced rat small intestinal injury is CD11a/CD18 and CD11b/CD18 co-dependant. Gut 50:629-635.

    Article  PubMed  Google Scholar 

  30. Ramamoorthy C., S. S. Sasaki, D. L. Su, S. R. Sharar, J. M. Harlan, and R. K. Winn. 1997. CD18 adhesion blockade decreases bacterial clearance and neurophil recruitment after intrapulmonary E. colibut not S. aureus. J. Leukoc. Biol. 61:167-172.

    PubMed  Google Scholar 

  31. Klebanoff, S. J. and R. A. Clark. 1978. The Neutrophil: Functions and Clinical Disorders. Elsevier Scientific, Amsterdam.

    Google Scholar 

  32. Venge P. 1990. The human eosinophil in inflammation. Agents Actions 29:122-126.

    PubMed  Google Scholar 

  33. Nègre, M., H. R. Schulten, M. Gennari, and D. Vindrola. 2001. Interaction of imidazolinone herbicides with soil humic acids. Experimental results and molecular modeling. J. Environ. Sci. Health, Part B 36:107-125.

    Google Scholar 

  34. Sato, T., Y. Ose, H. Nagase, and K. Hayase. 1987. Adsorption of mutagens by humic acid. Sci. Total Environ. 62:305-310.

    Article  PubMed  Google Scholar 

  35. Cozzi, R., M. Nicolai, P. Perticone, R. De Salvia, and F. Spuntarelli. 1993. Desmutagenic activity of natural humic acids: Inhibition of mitomycin C and maleic hydrazide mutagenicity. Mutat. Res. 299:37-44.

    PubMed  Google Scholar 

  36. Botes, M. E., J. Dekker, and C. E. J. van Rensburg. 2002. Phase I trial with oral oxihumate in HIV-infected patients. Drug Dev. Res. 57:34-39.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Pretoria, Pretoria, South Africa

    Gisela Käthe Jooné

  2. Department of Pharmacology, University of Pretoria, Pretoria, South Africa

    Constance Elizabeth Jansen van Rensburg

Authors
  1. Gisela Käthe Jooné
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Constance Elizabeth Jansen van Rensburg
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jooné, G.K., van Rensburg, C.E.J. An In Vitro Investigation of the Anti-Inflammatory Properties of Potassium Humate. Inflammation 28, 169–174 (2004). https://doi.org/10.1023/B:IFLA.0000039563.90066.5d

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:IFLA.0000039563.90066.5d

Search

Navigation