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Devil's Claw

Botanical Name: Harpagophytum procumbens , DC ex Meissner.
Pharmacopoeial Name: Harpagophyti radix.
Common Names: Devil’s claw, grapple plant, Cape grapple plant.

herb description



Parts Used

Secondary roots (tuber).

Common Forms

  • Dried:   Cut/powdered secondary root, containing not less than 1.2% harpagoside.

  • Tincture, Fluid Extract,   Hydroethanolic extracts 1:2, 1:3, 1:5 in 25% ethanol.

  • Standardized Extract:   Tablets or capsules, standardized 6:1 to 9:1 on 8.5% harpagoside. (WS 1531, Schwabe GmbH) or 1.5:1 to 2.5:1 standardized at 2.5% harpagoside (Doloteffin, Ardeypharm GmbH).

interactions review

Strategic Considerations

Devil's claw, a South African native, has been used in Western Europe for chronic arthritic conditions for several decades. The root tubers are bitter, containing iridoid glycosides, principally harpagoside. 1 The bitter nature of the remedy, suggested by Weiss 2 as comparable to gentian, led the German Commission E to approve its use for dyspepsia and loss of appetite. 3 In practice, however, it is only used for atonic digestion secondary to or associated with a primary arthritic condition. The European Scientific Cooperative on Phytotherapy (ESCOP) indications are for low back pain and osteoarthritis. 4,5There is positive clinical trial evidence as well as pharmacological support for the use of the herb in painful, chronic arthritic conditions. Most of the trials to date have been German or French and recently reviewed. 6-8Neither of the European therapeutic monographs notes any interactions between devil's claw and pharmaceutical drugs.

Pharmacologically, devil's claw has three principal areas of action: anti-inflammatory and analgesic, antiarrhythmic and hypotensive, and bitter tonic. Data regarding mechanism of the anti-inflammatory action has been conflicting, with initial studies suggesting a nonecosanoid mechanism because animal models of inflammation did not respond to the extract, although some direct effect on lipoxygenase and cyclooxygenase (COX) pathways was noted. 9-11More recent studies suggest that there may be a downregulation of inducible COX-2 and inducible nitric oxide synthase (iNOS), as well as a similar effect on tumor necrosis factor alpha (TNF-α) transcription, probably resulting from upstream effects on activating protein-1 (AP-1). 12-15This is consistent with the efficacy of the herb as a chronic, rather than acute, anti-inflammatory and analgesic agent operating through different pathways than the nonsteroidal anti-inflammatory drug (NSAID)–type direct effects on arachidonic acid metabolism. 16 Parallels with other botanical derivatives exist, and evidence is emerging for modulation of nuclear factor kappa B (NF-κB), 17 as well as the metalloproteinase TIMP-2. 18 Mechanism aside, clinical trials on the anti-inflammatory effects of devil's claw have revealed useful data relating to coadministration with several different NSAIDs and in clinical populations with chronic arthritic complaints using long-term NSAID therapy for management. This is a primary area for integrative use of the herb.

The cardiovascular effects of devil's claw have not been studied in humans, although studies of ex vivo Langendorff preparations (rabbit heart) and live rats strongly suggest the potential for protection against arrhythmias, including those induced by digoxin, together with a biphasic dose-response on heart rate. 19-21Interestingly, harpagoside did not reproduce the electrophysiological effects of whole-plant extract. The same researchers noted a hypotensive reaction to the extract in normotensive rats, but only with intraperitoneal administration of high doses. Further studies on this aspect of the herb's pharmacology have not been published, and devil's claw clearly is a complex remedy that is not fully understood. Traditional South African indications include seizures, and some scientific corroboration of this has been found in a murine model. 22 Meanwhile, monitoring heart rate and blood pressure in patients with either preexisting hypotension or disturbances of rate or rhythm during early stages of administration of the herb may be prudent.

Effects on Drug Metabolism and Bioavailability

The bitter tonic aspects of the herb suggest that a potential for stimulation of hepatobiliary activity, but studies of the generic effect of bitters on drug metabolism and detoxification systems are unavailable, and pharmacokinetic interactions with devil's claw have not been reported to date. A single in vitro screening study of the effect of the herb on a mixture of human recombinant drug–metabolizing enzymes derived from baculovirus-infected insect cells suggested a potential inhibition of cytochrome P450 (CYP450) by devil's claw extracts. 23

herb-drug interactions
Nonsteroidal Anti-Inflammatory Drugs and Related Antiarthritic Medications
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Warfarin and Related Oral Vitamin K Antagonist Anticoagulants
  • 1.Boje K, Lechtenberg M, Nahrstedt A. New and known iridoid- and phenylethanoid glycosides from Harpagophytum procumbens and their in vitro inhibition of human leukocyte elastase. Planta Med 2003;69:820-825.View Abstract
  • 2.Weiss R. Herbal Medicine. Meuss A, Translator. 6th ed. Beaconsfield, UK: Beaconsfield Publishers Ltd; 1988.
  • 3.Blumenthal M, Busse W, Goldberg A et al. The Complete German Commission E Monographs. Austin, Texas: American Botanical Council: Integrative Medicine Communications; 1998.
  • 4.ESCOP. Harpagophyti Radix. ESCOP Monographs: The Scientific Foundation for Herbal Medicinal Products. 2nd ed. Exeter, UK: European Scientific Cooperative on Phytotherapy and Thieme; 2003:233-240.
  • 5.Chrubasik S. Addendum to the ESCOP monograph on Harpagophytum procumbens. Phytomedicine 2004; 11:691-695.View Abstract
  • 6.Setty AR, Sigal LH. Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects. Semin Arthritis Rheum 2005;34:773-784.View Abstract
  • 7.Gagnier JJ, Chrubasik S, Manheimer E. Harpgophytum procumbens for osteoarthritis and low back pain: a systematic review. BMC Complement Altern Med 2004;4:13.View Abstract
  • 8.Gagnier J, Vantulder M, Berman B, Bombardier C. Herbal medicine for low back pain. Cochrane Database Syst Rev 2006:CD004504.
  • 9.Fontaine J, Elchami AA, Vanhaelen M, Vanhaelen-Fastre R. [Biological analysis of Harpagophytum procumbens DC. II. Pharmacological analysis of the effects of harpagoside, harpagide and harpagogenine on the isolated guinea-pig ileum (author’s translation)]. J Pharm Belg 1981;36:321-324.View Abstract
  • 10.Grahame R, Robinson BV. Devil’s claw (Harpagophytum procumbens): pharmacological and clinical studies. Ann Rheum Dis 1981;40:632.
  • 11.Whitehouse LW, Znamirowska M, Paul CJ. Devil’s claw (Harpagophytum procumbens): no evidence for anti-inflammatory activity in the treatment of arthritic disease. Can Med Assoc J 1983;129:249-251.
  • 12.Fiebich BL, Heinrich M, Hiller KO, Kammerer N. Inhibition of TNF-α synthesis in LPS-stimulated primary human monocytes by Harpagophytum extract SteiHap 69. Phytomedicine 2001;8:28-30.View Abstract
  • 13.Loew D, Mollerfeld J, Schrodter A et al. Investigations on the pharmacokinetic properties of Harpagophytum extracts and their effects on eicosanoid biosynthesis in vitro and ex vivo. Clin Pharmacol Ther 2001;69:356-364.View Abstract
  • 14.Jang MH, Lim S, Han SM et al. Harpagophytum procumbens suppresses lipopolysaccharide-stimulated expressions of cyclooxygenase-2 and inducible nitric oxide synthase in fibroblast cell line L929. J Pharmacol Sci 2003;93:367-371.View Abstract
  • 15.Kundu JK, Mossanda KS, Na H-K, 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 2005;218:21-31.View Abstract
  • 16.Moussard C, Alber D, Toubin MM et al. 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;46:283-286.View Abstract
  • 17.Huang TH-W, Tran VH, Duke RK et al. Harpagoside suppresses lipopolysaccharide-induced iNOS and COX-2 expression through inhibition of NF-κB activation. J Ethnopharmacol 2006;104:149-155.
  • 18.Chrubasik JE, Lindhorst E, Neumann E et al. Potential molecular basis of the chondroprotective effect of Harpagophytum procumbens. Phytomedicine 2006;13:598-600.View Abstract
  • 19.Circosta C, Occhiuto F, Ragusa S et al. A drug used in traditional medicine: Harpagophytum procumbens DC. II. Cardiovascular activity. J Ethnopharmacol 1984;11:259-274.View Abstract
  • 20.Costa De Pasquale R, Busa G, Circosta C et al. A drug used in traditional medicine: Harpagophytum procumbens DC. III. Effects on hyperkinetic ventricular arrhythmias by reperfusion. J Ethnopharmacol 1985;13:193-199.View Abstract
  • 21.Occhiuto F, Circosta C, Ragusa S et al. A drug used in traditional medicine: Harpagophytum procumbens DC. IV. Effects on some isolated muscle preparations. J Ethnopharmacol 1985;13:201-208.View Abstract
  • 22.Mahomed IM, Ojewole JAO. Anticonvulsant activity of Harpagophytum procumbens DC [Pedaliaceae] secondary root aqueous extract in mice. Brain Res Bull 2006;69:57-62.
  • 23.Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;18:2273-2281.View Abstract
  • 24.Chrubasik S, Conradt C, Black A. The quality of clinical trials with Harpagophytum procumbens. Phytomedicine 2003;10:613-623.View Abstract
  • 25.Chrubasik S, Junck H, Breitschwerdt H et al. 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;16:118-129.View Abstract
  • 26.Chrubasik S, Model A, Black A, Pollak S. A randomized double-blind pilot study comparing Doloteffin and Vioxx in the treatment of low back pain. Rheumatology (Oxford) 2003;42:141-148.View Abstract
  • 27.Chrubasik S, Pollak S, Fiebich B. Harpagophytum extracts. Clin Pharmacol Ther 2002;71:104-105.View Abstract
  • 28.Chrubasik S, Sporer F, Dillmann-Marschner R et al. Physicochemical properties of harpagoside and its in vitro release from Harpagophytum procumbens extract tablets. Phytomedicine 2000;6:469-473.View Abstract
  • 29.Chrubasik S, Thanner J, Kunzel O et al. Comparison of outcome measures during treatment with the proprietary Harpagophytum extract doloteffin in patients with pain in the lower back, knee or hip. Phytomedicine 2002;9:181-194.
  • 30.Chantre P, Cappelaere A, Leblan D et al. Efficacy and tolerance of Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis. Phytomedicine 2000;7:177-183.View Abstract
  • 31.Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001;286:954-959.View Abstract
  • 32.Zhao SZ, Reynolds MW, Lejkowith J et al. A comparison of renal-related adverse drug reactions between rofecoxib and celecoxib, based on the World Health Organization/Uppsala Monitoring Centre safety database. Clin Ther 2001;23:1478-1491.
  • 33.Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements: a 5-year toxicological study (1991-1995). Drug Saf 1997;17:342-356.View Abstract
  • 34.Fugh-Berman A, Ernst E. Herb-drug interactions: review and assessment of report reliability. Br J Clin Pharmacol 2001;52:587-595.View Abstract