For more than 50 years preparations of H. procumbens [devil’s claw, Figure 1(E)] have been used in Europe for the treatment of rheumatic entities. Devil’s claw is native to the southern part of the African continent and may be found in Namibia, Botswana, South Africa, Angola, Zambia, and Zimbabwe [Anonymous, 2008; Qi et al. 2006]. Historically, devil’s claw has been used as an analgesic, for fevers and allergies, appetite stimulation, wounds and skin rashes, dyspepsia, liver and kidney disorders, as diuretic and sedative, and to treat degenerative disorders of the musculoskeletal system [Blumenthal, 1998; Stewart and Cole, 2005; Qi et al. 2006; Ragusa et al. 1984]. The major chemical constituents of devil’s claw are iridoid glycosides (primarily harpagoside, harpagide, and procumbide), sugars (mainly the tetrasaccharide, stachyose), triterpenoids (oleanolic and ursolic acid), phytosterols (primarily β-sitosterol), aromatic acids (caffeic, cinnamic, and chlorogenic acids), and flavonoids such as luteolin and kaempferol [Bradley, 1992]. Harpagoside, harpagide, and procumbide, found in the tubers of the plant, appear to be the most therapeutically important constituents. Whole-plant extracts appear to have a better therapeutic effect than those prepared from isolated parts [Qi et al. 2006]. A large body of evidence indicates that devil’s claw may be an effective treatment for OA because of its pain-relieving and anti-inflammatory actions. Higher concentrations of serum oxygen-free radicals prevalent with arthritis may alter the oxidant/antioxidant balance, thus facilitating lipid peroxidation and leading to tissue damage [Jaswal et al. 2003]. Devil’s claw extract has been shown to increase superoxide dismutase, catalase, glutathione peroxidase enzyme activities in a dose-dependent manner and a reduction in lipid peroxidation was also noted in vivo, which contribute to its antioxidant effects [Bhattacharya and Bhattacharya, 1998]. The flavonoids and plant phenols present in devil’s claw extracts may be the constituents responsible for the observed antioxidant activity [Dugas et al. 2000; Sawa et al. 1999]. Devil’s claw has been found to scavenge both superoxide and peroxyl radicals [Langmead et al. 2002]. A recent study also showed that both root tuber extract of devil’s claw and tincture are effective as free radical scavengers and inhibit LPS-induced nitrite levels in RAW 264.6 macrophages [Grant et al. 2009]. Significant antioxidant effects by an aqueous extract of devil’s claw and by the flavonoid constituents lutteolin and kaempferol have also been noted [Betancor-Fernández et al. 2003]. A dried aqueous extract (5 and 10 mg/kg) of devil’s claw has been shown to exert a significant dose-dependent analgesic and anti-inflammatory effect in rats. However, carrageenan-induced paw edema was not affected by harpagoside, suggesting harpagoside may not have an anti-inflammatory effect at least in the doses used in vivo [Lanhers et al. 1992]. In vitro data also demonstrated that the active principle (sum of coactive constituents) of devil’s claw inhibits not only inflammatory mediators such as iNOS and COX-2 mediated PGE2 production [Fiebich et al. 2001; Jang et al. 2003; Huang et al. 2005] or leukotriene release [Loew et al. 2001] but also mediators of cartilage destruction, such as TNFα, IL-1β, IL-6, MMPs, NO [Fiebich et al. 2001; Huang et al. 2005; Schulze-Tanzil et al. 2004a], and elastase [Boje et al. 2003]. Reported chondroprotective effects of devil’s claw may be due to suppression of NF-κB activation, thereby inhibiting inflammation [Huang et al. 2005].
Devil’s claw extract appears to be safe when used in appropriate dosages. The side effects are few, usually limited to gastrointestinal upset, dyspepsia and loss of taste; no long-term toxicities or drug-interactions are known [Vlachojannis et al. 2008]. Devil’s claw extract exerts a peripheral analgesic effect as it has been demonstrated to decrease pain in knee and hip OA [reviewed in Ameye and Chee, 2006; Chrubasik et al. 2002; Chantre et al. 2000]. The effectiveness of certain devil’s claw preparations has been tested with a daily dose of 360 mg of harpagoside (a coactive ingredient) in the treatment of painful OA of the hip, knee and nonspecific low back pain. Multivariate analysis confirmed that in all groups, both the generic and disease-specific outcome measures improved by week 4 and further by week 8 [Chrubasik et al. 2002]. H. procumbens powder was equally effective as diacerhein in reducing pain as measured using a 100 mm VAS. This study constitutes moderate evidence that 4 months’ daily use of 2610 mg H. procumbens powder is not significantly different from 100 mg diacerhein, producing comparable improvements in pain [Leblan et al. 2000]. Studies on devil’s claw extracts, containing 50–100 mg harpagoside daily, have shown the best results [Brien et al. 2006]. In a clinical study, 89 patients with OA were randomized to receive placebo or devil’s claw at a total daily dose of 2010 mg/day for 8 weeks. The study identified that after 30 and 60 days of treatment, patients who received devil’s claw had a significant reduction in pain (p = 0.018 after 30 days and p = 0.012 after 60 days of treatment) compared with placebo [Lecomte and Costa, 1992]. Effectiveness, safety and tolerability of Harpagophytum was studied in rheumatic disorders including OA for 8 weeks (259 patients). There were statistically significant (p < 0.0001) improvements in patient assessment of global pain, stiffness, function and quality of life. There were also statistically significant reductions in mean pain scores for hand, wrist, elbow, shoulder, hip, knee and back pain [Warnock et al. 2007]. Numerous trials have been conducted using several devil’s claw extracts for OA (Table 1 and rheumatism [Rutten and Schafer, 2000; Bélaiche,1982; Lecomte and Costa, 1992; Schmelz et al.1997; Frerick et al. 2001; Chrubasik et al. 2002; Chantre et al. 2000; Leblan et al. 2000; Warnock et al. 2007]. Unfortunately, the results of many of the studies are of questionable value because of methodological flaws. However, devil’s claw appears to be effective in the reduction of pain. More high-quality trials are needed to assess the effectiveness and efficacy of devil’s claw to determine whether this is a beneficial remedy for the treatment of OA.