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Devil's claw (Harpagophytum procumbens)


Devil's Claw (Harpagophytum procumbens) Image
Synonyms / Common Names / Related Terms
!ao!ao, //khuripe//khams (Damara/Nama), //xemta='eisa, //xsamsa-//oro (Kung bushman), 6-acetylacteoside, acteoside, afrikanische Teufelskralle (German), Algophytum®, aromatic acids, arpagofito (Italian), Arthrosetten H®, Arthrotabsm®, Artigel®, artiglio del diavolo, Artosan®, beta-sitosterol, burdock, caffeic acid, cinnamic acid, Defencid®, Devil's Claw Capsule®, Devil's Claw Secondary Root®, Devil's Claw Vegicaps®, Doloteffin®, duiwelsklou (Afrikaans), ekatata (Ndonga, Kwangali), elyata (Kwanyama), Fitokey Harpagophytum®, flavonoids, grapple plant, griffe du diable (French), gum resins, Hariosen®, Harpadol®, HarpagoMega®, Harpagon®, Harpagophyti radix (Latin), Harpagophytum procumbens, Harpagophytum zeyheri, harpagoquinone, harpagoside, iridoid glycosides, isoacteoside, Jucurba N®, kloudoring (Afrikaans), likakata (Gciriku, Shambyu), otjihangatene (Herero), pagoside, Pedaliaceae (family), procumbide, procumboside, Rheuma-Sern®, Rheuma-Tee®, Salus®, sengaparile (Senegalese), stigmasterol, Südafrikanische Teufelskralle (German), Trampelklette (German), triterpenes, Venustorn (Danish), Windhoek's root, wood spider.

Combination product examples: Arktophytum, Arthritic Pain Herbal Formula®, Devil's Claw Plus®, Lifesystem Herbal Formula 1 Arthritic Aid®, Lifesystem Herbal Formula 12 Willowbark®, Prost-1®, Harpagophytum®.

Mechanism of Action

Pharmacology:

  • Constituents: Potentially active chemical constituents of devil's claw include iridoid glycosides (2.2% total weight)30, harpagoside (0.5-1.6%)31, 8-p-coumaroylharpagide, 8-feruloylharpagide, 8-cinnamoylmyoporoside, pagoside, acteoside, isoacteoside, 6'-O-acetylacteoside, 2,6-diacetylacteoside, cinnamic acid, caffeic acid32,33,34, procumbide, and procumboside. Being present in H. procumbens and absent in H. zeyheri, the constituent 6-acetylacteoside allows distinction between the two species26,27,28. Other compounds include flavonoids, fatty acids, aromatic acids, harpagoquinone, stigmasterol, beta-sitosterol, triterpenes, sugars (over 50%), and gum resins.35
  • 5-Lipoxygenase biosynthesis inhibition activity: In in vitro studies, and two carbon dioxide extracts totally inhibited 5-lipoxygenase biosynthesis at a concentration of 51.8mg/L, although a convention extract did not show any inhibition.24
  • Analgesic properties: Administration of 20mg/kg harpagoside has been reported to produce an analgesic effect similar to that of phenylbutazone at 50mg/kg.1 Writhings and stretchings induced in rats by 1.2% acetic acid was significantly reduced after administration of an aqueous devil's claw extract (2.2% harpagoside).6 An aqueous Harpagphytum root extract given by intraperitoneal administration (200mg/kg) produced 53% protection.3
  • Anti-inflammatory properties: In various doses, devil's claw extracts have been reported to exert anti-inflammatory properties 1,2,3,4, while other studies did not confirm these results36,19. In acute conditions, such as carrageenan-induced edema, no or only slight activity was found1,2,36,19,29, while other research obtained a significant reduction of adriamycin-induced edema in rats with oral administration of powdered Harpagophytum root5. One investigation of carrageenaan-induced rat hind paw edema reported an efficacy of 1,200mg/kg, similar if that of indomethacin 10mg/kg.6 Anti-inflammatory effects in acute and chronic treatment of Freund's adjuvant-induced arthritis in rats have also been noted.7 Some research of the effects of Harpagophytum constituents on the stimulated release of inflammatory mediators from mouse peritoneal macrophages report that aucubin inhibits LCT4-release, but none of the iridoid glycosides significantly affect release of prostaglandin or other products of the COX-2 pathway, although most constituents (except harpagoside) demonstrate significant inhibition of stimulated TXB2 release.8 This contrasts with other findings, in which devil's claw did not alter the cyclooxygenase or 5-lipoxygenase pathways of eicosanoid biosynthesis.37 Its anti-inflammatory activities were thus postulated to be independent of arachidonic acid metabolism alteration.38 However, more recent investigations suggest that harpagoside may inhibit both arachidonic acid metabolism pathways when more complex test procedures are used.9,10,11 Specifically, downregulation of iNOS expression in rat mesangial cells by Harpagophytum extracts has been reported. Both an ethanolic extract12 and an aqueous extract13 prevented TNF-alpha synthesis; the latter, however, having a greater inhibitory effect on COX-2 pathway products. This was confirmed in subsequent research.14 Harpagophytum extracts showed inhibitory effects on phorbol ester-induced COX-2 expression in mouse skin15, as well as inhibition of TPA-induced COX-2 expression in human breast epthelial cells and in mouse skin16. The capability of Harpagophytum extract to suppress enhanced production of matrix-degrading enzymes (matrix metalloproteinases) via the inhibition of the synthesis of inflammatory cytokines has also been reported.17,18
  • Antimicrobial properties: A crude preparation of H. procumbens demonstrated antiplasmodial activity.25
  • Antioxidant properties: Antioxidant effects similar to selegiline-induced responses were found in rats treated with a 53% ethanolic Harpagophytum dry extract.22 Some animal experiments have reported antioxidant activity of H. procumbens22,23, although these results have not been confirmed by others5,39.
  • Cardiac and neuromuscular effects: A crude methanolic extract of devil's claw root demonstrated significant dose-dependent protection against arrhythmias in isolated rat hearts21, as well as isolated rabbit heart20. Effects of the methanolic extract of H. procumbens on smooth muscle may be due to a complex interaction of various constituents with the cholinergic receptor. While harpagoside antagonizes smooth muscle contractile responses to acetlycholine and BaCl2, harpagide increases the response at lower doses and antagonizes it at higher doses. This partial inhibition of BaCl2 experimentally may explain the protective effect of the extract to arrhythmias by interference of the mechanisms regulating influx of calcium into cells. Further studies are necessary to confirm this hypothesis.40,41,21,20

Pharmacodynamics/Kinetics:

  • Absorption: Harpagoside is stable in artificial gastric juices for about three hours and in intestinal juices for a period of six hours.42,43,9,10 Nonetheless, it has been proposed that gastric digestion may decrease the potency of devil's claw, be inactivated after acid hydrolysi3, and that enteric-coated preparations may maintain efficacy despite exposure to gastric acids. This suggestion is supported by animal research, in which anti-inflammatory effects could not be obtained by oral administration, but dose-dependent effects were observed with intraperitoneal and intraduodenal administration29,44. Harpagophytum tablets are highly soluble with an octanol-water distribution coefficient of approximately four.
  • Distribution: In a blood sample taken from a human two hours after ingesting a devil's claw extract containing 44mg harpagoside, the harpagoside level was 15.4ng/mL.45 Oral administration of a 600mg extract containing 25% harpagoside led to plasma harpagoside levels of 32.2ng/mL after 1.3 hours, which subsequently rapidly decreased. A second peak was observed after eight hours.
  • Elimination: Harpagoside elimination half-life has been reported as 5.6 hours.37 Transformation of iridoid glucosides by human fecal flora has been observed.46

References

  1. Eichler, O. and Koch, C. [Antiphlogistic, analgesic and spasmolytic effect of harpagoside, a glycoside from the root of Harpagophytum procumbens DC]. Arzneimittelforschung  1970;20(1):107-109. 4392498
  2. Erdos, A., Fontaine, R., Friehe, H., Durand, R., and Poppinghaus, T. [Contribution to the pharmacology and toxicology of different extracts as well as the harpagosid from Harpagophytum procumbens DC]. Planta Med 1978;34(1):97-108. 308666
  3. Lanhers, M. C., Fleurentin, J., Mortier, F., Vinche, A., and Younos, C. Anti-inflammatory and analgesic effects of an aqueous extract of Harpagophytum procumbens. Planta Med 1992;58(2):117-123. 1529021
  4. Grant, L., McBean, D. E., Fyfe, L., and Warnock, A. M. A review of the biological and potential therapeutic actions of Harpagophytum procumbens. Phytother Res 2007;21(3):199-209. 17128436
  5. Jadot G and Lecomte A. Activite anti-inflammatoire d'Harpagophytum procumbens DC. Lyon Mediteranee Med Sud-Est 1992;28:833-835.
  6. Baghdikian, B., Lanhers, M. C., Fleurentin, J., Ollivier, E., Maillard, C., Balansard, G., and Mortier, F. An analytical study, anti-inflammatory and analgesic effects of Harpagophytum procumbens and Harpagophytum zeyheri. Planta Med 1997;63(2):171-176. 9140234
  7. Andersen, M. L., Santos, E. H., Seabra, Mde L., da Silva, A. A., and Tufik, S. Evaluation of acute and chronic treatments with Harpagophytum procumbens on Freund's adjuvant-induced arthritis in rats. J Ethnopharmacol  2004;91(2-3):325-330. 15120457
  8. Benito PM, Lanza AM, Sen AM, and et al. Effects of Some Iridoids from Plant Origin on Arachidonic Acid Metabolism in Cellular Systems. Planta Med 2000;66(4):324-328.
  9. Chrubasik, S., Junck, H., Breitschwerdt, H., Conradt, C., and Zappe, H. Effectiveness of Harpagophytum extract WS 1531 in the treatment of exacerbation of low back pain: a randomized, placebo-controlled, double- blind study. Eur J Anaesthesiol  1999;16(2):118-129. 10101629
  10. Chrubasik S and Eisenberg E. Treatment of rheumatic pain with Kampo medicine in Europe. The Pain Clinic 1999;11(3):171.
  11. Kaszkin, M., Beck, K. F., Koch, E., Erdelmeier, C., Kusch, S., Pfeilschifter, J., and Loew, D. Downregulation of iNOS expression in rat mesangial cells by special extracts of Harpagophytum procumbens derives from harpagoside-dependent and independent effects. Phytomedicine  2004;11(7-8):585-595. 15636171
  12. Fiebich, B. L., Heinrich, M., Hiller, K. O., and Kammerer, N. Inhibition of TNF-alpha synthesis in LPS-stimulated primary human monocytes by Harpagophytum extract SteiHap 69. Phytomedicine  2001;8(1):28-30. 11292236
  13. Chrubasik S, Fiebich B, Black A, and et al. Treating low back pain with an extract of Harpagophytum procumbens that inhibits cytokine release. Eur J Anaesthesiol 2002;19:209.
  14. Jang, M. H., Lim, S., Han, S. M., Park, H. J., Shin, I., Kim, J. W., Kim, N. J., Lee, J. S., Kim, K. A., and Kim, C. J. Harpagophytum procumbens suppresses lipopolysaccharide-stimulated expressions of cyclooxygenase-2 and inducible nitric oxide synthase in fibroblast cell line L929. J Pharmacol Sci  2003;93(3):367-371. 14646256
  15. Kundu, J. K., Mossanda, K. S., Na, H. K., and Surh, Y. J. Inhibitory effects of the extracts of Sutherlandia frutescens (L.) R. Br. and Harpagophytum procumbens DC. on phorbol ester-induced COX-2 expression in mouse skin: AP-1 and CREB as potential upstream targets. Cancer Lett  1-31-2005;218(1):21-31. 15639337
  16. Na, H. K., Mossanda, K. S., Lee, J. Y., and Surh, Y. J. Inhibition of phorbol ester-induced COX-2 expression by some edible African plants. Biofactors 2004;21(1-4):149-153. 15630188
  17. Schulze-Tanzil, G., Hansen, C., and Shakibaei, M. [Effect of a Harpagophytum procumbens DC extract on matrix metalloproteinases in human chondrocytes in vitro]. Arzneimittelforschung  2004;54(4):213-220. 15146934
  18. Spelman, K., Burns, J., Nichols, D., Winters, N., Ottersberg, S., and Tenborg, M. Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators. Altern Med Rev 2006;11(2):128-150. 16813462
  19. Grahame, R. and Robinson, B. V. Devils's claw (Harpagophytum procumbens): pharmacological and clinical studies. Ann Rheum Dis 1981;40(6):632. 7332387
  20. Circosta, C., Occhiuto, F., Ragusa, S., Trovato, A., Tumino, G., Briguglio, F., and de Pasquale, A. A drug used in traditional medicine: Harpagophytum procumbens DC. II. Cardiovascular activity. J Ethnopharmacol  1984;11(3):259-274. 6482477
  21. Costa De Pasquale, R, Busa, G., Circosta, C., Iauk, L., Ragusa, S., Ficarra, P., and Occhiuto, F. A drug used in traditional medicine: Harpagophytum procumbens DC. III. Effects on hyperkinetic ventricular arrhythmias by reperfusion. J Ethnopharmacol  1985;13(2):193-199. 4021516
  22. Bhattacharya A and Bhattacharya SK. Anti-oxidative activity of Harpagophytum procumbens. Br J Phytother 1998;72:68-71.
  23. Langmead L, Dawson C, Hawkins C, and et al. Antioxidant effects of herbal therapies used by patients with inflammatory bowel disease: an in vitro study. Aliment Pharmacol Ther 2002;16(2):197-205.
  24. Gunther, M., Laufer, S., and Schmidt, P. C. High anti-inflammatory activity of harpagoside-enriched extracts obtained from solvent-modified super- and subcritical carbon dioxide extractions of the roots of Harpagophytum procumbens. Phytochem Anal  2006;17(1):1-7. 16454469
  25. Clarkson, C., Campbell, W. E., and Smith, P. In vitro antiplasmodial activity of abietane and totarane diterpenes isolated from Harpagophytum procumbens (devil's claw). Planta Med 2003;69(8):720-724. 14531022
  26. Chrubasik, S. Addendum to the ESCOP monograph on Harpagophytum procumbens. Phytomedicine  2004;11(7-8):691-695. 15636187
  27. Chrubasik, S. [Devil's claw extract as an example of the effectiveness of herbal analgesics]. Orthopade 2004;33(7):804-808. 15150687
  28. Chrubasik, S., Conradt, C., and Roufogalis, B. D. Effectiveness of Harpagophytum extracts and clinical efficacy. Phytother Res  2004;18(2):187-189. 15022177
  29. Whitehouse, L. W., Znamirowska, M., and Paul, C. J. Devil's Claw (Harpagophytum procumbens): no evidence for anti-inflammatory activity in the treatment of arthritic disease. Can Med Assoc J 8-1-1983;129(3):249-251. 6407745
  30. Kikuchi T. New iridoid glucosides from Harpagophytum procumbens. Chem Pharm Bull 1983;31:2296-2301.
  31. Tunmann P and Lux R. Zur Kenntnis der Inhaltsstoffe aus der Wurzel von Harpagophytum procumbens DC. DAZ 1962;102(40):1274-1275.
  32. Ficarra P, Ficarra R, Tommasini A, and et al. [HPLC analysis of a drug in traditional medicine: Harpagophytum procumbens DC. I]. Boll Chim Farm 1986;125(7):250-253.
  33. Boje, K., Lechtenberg, M., and Nahrstedt, A. New and known iridoid- and phenylethanoid glycosides from Harpagophytum procumbens and their in vitro inhibition of human leukocyte elastase. Planta Med 2003;69(9):820-825. 14598207
  34. Munkombwe, N. M. Acetylated phenolic glycosides from Harpagophytum procumbens. Phytochemistry 2003;62(8):1231-1234. 12648542
  35. Tunmann P and Bauersfeld HJ. Über weitere Inhaltsstoffe der Wurzel von Harpagophytum procumbens DC. Arch Pharm (Weinheim) 1975;308(8):655-657.
  36. McLeod, D. W., Revell, P., and Robinson, B. V. Investigations of Harpagophytum procumbens (Devil's Claw) in the treatment of experimental inflammation and arthritis in the rat [proceedings]. Br J Pharmacol 1979;66(1):140P-141P. 454934
  37. Loew, D., Mollerfeld, J., Schrodter, A., Puttkammer, S., and Kaszkin, M. Investigations on the pharmacokinetic properties of Harpagophytum extracts and their effects on eicosanoid biosynthesis in vitro and ex vivo. Clin Pharmacol Ther  2001;69(5):356-364. 11372004
  38. Moussard, C., Alber, D., Toubin, M. M., Thevenon, N., and Henry, J. C. A drug used in traditional medicine, Harpagophytum procumbens: no evidence for NSAID-like effect on whole blood eicosanoid production in human. Prostaglandins Leukot Essent Fatty Acids 1992;46(4):283-286. 1409765
  39. Betancor-Fernandez, A., Perez-Galvez, A., Sies, H., and Stahl, W. Screening pharmaceutical preparations containing extracts of turmeric rhizome, artichoke leaf, devil's claw root and garlic or salmon oil for antioxidant capacity. J Pharm Pharmacol  2003;55(7):981-986. 12906755
  40. Fontaine, J., Elchami, A. A., Vanhaelen, M., and Vanhaelen-Fastre, R. [Biological analysis of Harpagophytum procumbens D.C. II. Pharmacological analysis of the effects of harpagoside, harpagide and harpagogenine on the isolated guinea-pig ileum (author's transl)]. J Pharm Belg  1981;36(5):321-324. 7310625
  41. Occhiuto, F., Circosta, C., Ragusa, S., Ficarra, P., and Costa, De Pasquale. A drug used in traditional medicine: Harpagophytum procumbens DC. IV. Effects on some isolated muscle preparations. J Ethnopharmacol  1985;13(2):201-208. 4021517
  42. Ernst, E. and Chrubasik, S. Phyto-anti-inflammatories. A systematic review of randomized, placebo- controlled, double-blind trials. Rheum Dis Clin North Am 2000;26(1):13-27. 10680191
  43. Chrubasik, S., Sporer, F., Dillmann-Marschner, R., Friedmann, A., and Wink, M. Physicochemical properties of harpagoside and its in vitro release from Harpagophytum procumbens extract tablets. Phytomedicine 2000;6(6):469-473. 10715851
  44. Soulimani, R., Younos, C., Mortier, F., and Derrieu, C. The role of stomachal digestion on the pharmacological activity of plant extracts, using as an example extracts of Harpagophytum procumbens. Can J Physiol Pharmacol 1994;72(12):1532-1536. 7736345
  45. Loew D, Schuster O, and Möllerfeld J. Stabilität und biopharmazeutische Qualität. Voraussetzung für Bioverfügbarkeit von Harpagophytum procumbens. In: Loew D and Rietbrock N. Phytopharmaka II. Forschung und klinische Anwendung. Darmstadt: Forschung und klinische Anwendung;1996.
  46. Baghdikian, B., Guiraud-Dauriac, H., Ollivier, E., N'Guyen, A., Dumenil, G., and Balansard, G. Formation of nitrogen-containing metabolites from the main iridoids of Harpagophytum procumbens and H. zeyheri by human intestinal bacteria. Planta Med 1999;65(2):164-166. 10193209




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