Constituents

The most important actives are considered to be the bitter iridoids, harpagide and harpagoside (Fig. 21.1), with 8-O–p-coumaroylharpagide, procumbide, 6’-O–p-coumaroylprocumbide, pagide and procumboside; the triterpenoids oleanolic and ursolic acids, β-sitosterol and a glycoside harproside. Other compounds present include phenylethyl glycosides such as verbascoside and isoacteoside, polyphenolic acids (caffeic, cinnamic, and chlorogenic acids), and flavonoids such as luteolin and kaempferol. According to the Eur. Ph. the drug must contain ≥ 1.2% harpagide and harpagoside, expressed as harpagoside.

Fig. 21.1

Therapeutic uses and available evidence

In Europe, a tea (made from a dose of about 1.5 g/day of the powdered drug) has been used for the treatment of dyspeptic disorders such as indigestion and lack of appetite. This effect is due to the presence of bitter glycosides, the iridoids, which are present in large amounts.

Most pharmacological and clinical research has been conducted using standardized extracts for the treatment of rheumatic conditions and lower back pain. Several clinical studies, including some placebo-controlled double-blind trials, demonstrate the superiority of these extracts to placebo in patients with osteoarthritis, non-radicular back pain and other forms of chronic and acute pain. Other studies show their therapeutic equivalence to conventional forms of treatment. Devil’s claw is generally well tolerated and appears to be a suitable alternative to NSAIDs, which often have gastrointestinal side effects (for review, see Barnes 2009, Cameron et al 2009).

The mechanism of action is not fully known: fractions of the extract containing the highest concentration of harpagoside inhibited COX-1 and COX-2 activity and greatly inhibited NO production, whereas in contrast, the fraction containing mainly the other iridoids increased COX-2 and did not alter NO and COX-1 activities. A fraction containing mainly cinnamic acid was able to reduce only NO production (Anauate et al 2010). An extract of Harpagophytum procumbens showed a significant antiinflammatory effect in the rat adjuvant-induced chronic arthritis model, and harpagoside dose-dependently suppressed the lipopolysaccharide (LPS)-induced production of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in mouse macrophage cells (Inaba et al 2010). These demonstrate that harpagoside is probably the main active constituent responsible for the effect of devil’s claw, but that other components from the crude extract can antagonize or increase the synthesis of inflammatory mediators. In summary, both the pharmacological mechanism and the compounds responsible for this activity have to be investigated further, and by in vivo methods. There are implications for the production methods for preparing devil’s claw extracts, and a recent study of the antiinflammatory activity of various commercial products has demonstrated that there is a great difference in their composition, and concludes that the harpagoside content is not a reliable method of predicting the therapeutic efficacy (Ouitas and Heard 2010). Extracts of devil’s claw are generally well tolerated but should not be used for patients with gastric or duodenal ulceration. The aqueous extract possesses spasmogenic, uterotonic action on rat uterine muscles (Mahomed and Ojewole 2009), leading credence to the folkloric obstetric uses, but suggesting that it should be avoided in pregnant women. Side effects include minor gastrointestinal upsets.

Constituents

Antiinflammatory constituents isolated from rosehip extracts include the triterpene acids, oleanolic, betulinic and ursolic acids; oleic, linoleic and alpha-linolenic acids, and a series of galactolipids which are thought to be a major contributor to the effects (Chrubasik et al 2008b).

Therapeutic uses and available evidence

Traditionally, rose hips were used as a source of vitamin C and were made into syrups for that purpose, but modern use is now focused on their antiinflammatory effects (for review, see Chrubasik et al 2008a). In a pilot surveillance study which included 152 patients with acute exacerbations of chronic pain, mainly of the lower back and knee, patients were recommended rose hip and seed powder at a dose providing up to 3 mg of galactolipid/day for up to 54 weeks. Multivariate analysis suggested an appreciable overall improvement, irrespective of type of pain, and this was reflected for most of the individual measures. There were no serious adverse events (Chrubasik et al 2008b). In a recent double-blind placebo-controlled trial of 89 patients with rheumatoid arthritis, treatment with encapsulated rose-hip powder 5 g daily for 6 months suggested that patients with rheumatoid arthritis may benefit from additional treatment with rose hip (Willich et al 2010). A study comparing powdered rose hip with and without the seeds found that extracts derived from rose hip without fruits were more effective in assays carried out for inhibition of COX-1, COX-2 and 5-LOX-mediated leukotriene B(4) formation, as well as for antioxidant capacity (Wenzig et al 2008). Extracts of rosehips have displayed potent antiinflammatory and antinociceptive activities in several in vivo experimental models (Deliorman Orhan et al 2007