Friday, July 31, 2020

DEVIL'S CLAW -- Harpagophytum procumbens (Burch.) DC ex. Meisn. (Pedaliaceae) ++

HERBAL

MEDICINAL

PLANT

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Devils Claw Harpagophytum Procumbens Photograph by Tierbild ...

DEVIL’S CLAW  

Harpagophytum procumbens  (Burch.) DC ex. Meisn. (Pedaliaceae) ++  

 

 

BY

 

RETTODWIKART THENU





DEVIL’S CLAW

(dev’uhlz claw)

 

 

Harpagophytum procumbens  (Burch.) DC ex. Meisn. (Pedaliaceae) ++

 

SUMMARY AND PHARMACEUTICAL COMMENT

 

The botanical name Harpagophytum means ‘hook plant’ in Greek, after the hook-covered fruits of the plant. Devil’s claw is native to southern Africa and has been used traditionally as a bitter tonic for digestive disturbances, febrile illnesses and allergic reactions, and to relieve pain (Mills & Bone 2000). It has been used in Europe for the treatment of rheumatic conditions for over 50 years, and was first cited in the literature by Zorn at the University of Jena, Germany, who described his observations on the antiphlogistic and anti-arthritic effects after administration of oral aqueous extracts prepared from the secondary roots of H. procumbens in patients suffering from arthritides (Chrubasik et al 2006).

 

The chemistry of devil’s claw has been well documented. The iridoid constituents are thought to be responsible for the reputed anti-inflammatory activity of devil’s claw, although it is not known precisely which of these are the most important for pharmacological activity, and the importance of other compounds. There is conflicting evidence from in vitro, animal and human studies regarding the anti-inflammatory activity of devil’s claw and possible mechanisms of action.

Several randomised trials using devil’s claw extracts standardised on harpagoside content have reported superiority over placebo for some aspects of low back pain and rheumatic complaints. However, some studies used nonstandard outcome measures and carried out several post-hoc analyses. Further studies have used recognised, predefined outcome measures to establish the therapeutic value of standardised devil’s claw extracts in patients with arthritic and rheumatic conditions.

On the basis of randomised controlled trials involving patients with arthritic and rheumatic disorders, devil’s claw extracts appear to have a favourable short-term adverse effect profile when taken in recommended doses. Mild, transient gastrointestinal effects, such as diarrhoea and flatulence, may occur. Chronic toxicity studies and clinical experience with prolonged use are lacking, so the effects of long-term use are not known. On this basis, and in view of the possible cardioactivity of devil’s claw, devil’s claw should not be used for long periods of time at doses higher than recommended.

Further studies involving large numbers of patients are required.

 

TRADE NAMES

Devil's Claw (available from a number of manufacturers),

Devil's Claw Secondary Root, Devil's Claw Root Tuber

 

OTHER COMMON NAMES

Grapple Plant, Wood Spider

 

DESCRIPTION

MEDICINAL PARTS: The medicinal parts are the dried tubular secondary roots and the thick lateral tubers.

FLOWER AND FRUIT: The flowers grow on short pedicles in the leaf axils and are solitary, large and foxglove-like. The petals are pale-pink to crimson. The seed capsules are bivalvular, compressed at the sides and ovate. The capsules are 7 to 20 cm long, 6 cm in diameter, and very woody with longitudinally striped rind. They have a double row of elastic, armL ike, branched appendages with an anchor-like hook. The capsules contain about 50 dark oblong seeds with a rough surface.

LEAVES, STEM AND ROOT: The plant is perennial and leafy. It has a branched root system and branched, prostrate shoots 1 to 1.5 m long. The leaves are petiolate and lobed, and may be opposite or alternate. The aerial parts of the plant die back in the dry season. The tuber (storage) roots are formed from the main and lateral roots. The main roots have obtuse, quadrangular, upright collar-like sections, 10 to 20 cm long and 30 to 60 cm thick, which are covered in a fissured cork layer. The nodes of the lateral roots are up to 60 mm thick and 20 cm long, and are light-brown to red-brown on the outside. The roots extend out to an area of about 150 cm around the plant and grow down to a depth of 30 to 60 cm.

CHARACTERISTICS: The dried, pulverized secondary tubers and roots are yellowish-gray to bright pink and horn-like in their hardness. They have a bitter taste.

HABITAT: The plant originated in South Africa and Namibia, and has spread throughout the Savannas and the Kalahari.

PRODUCTION: Devil's Claw root consists of the dried lateral roots and secondary tubers of Harpagophytum procumbens. The lateral roots are cut into slices or pieces, or pulverized immediately after digging because they harden and become very difficult to cut once dry.

 

SPECIES (FAMILY)

Harpagophytum procumbens  (Burch.) DC ex. Meisn. (Pedaliaceae) ++

 

SYNONYM(S)

Uncaria procumbens Burch.

Harpagophytum, Harpagophytum burchelii Decne, Grapple Plant, Wood Spider

 

ORIGIN

Devil’s claw grows wild in southwest Africa.

 

 

PHARMACOPODIAL AND OTHER MONOGRAPHS

BHC 1992(G6)

BHMA 2003(G66)

BHP 1996(G9)

BP 2007(G84)

Complete German Commission E(G3)

ESCOP 2003(G76)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

 

LEGAL CATEGORY (LICENSED PRODUCTS)

Devil's claw is not included in the GSL.(G37)

 

CONSTITUENTS

See also General Reference G2.

Carbohydrates Fructose, galactose, glucose and myo-inositol (monosaccharides), raffinose, stachyose (46%) and sucrose (oligosaccharides).(1)

Diterpenes (þ)-8,11,13-totaratriene-12,13-diol and (þ)-8,11,13- abietatrien-12-ol.(2)

Iridoids Harpagoside (1–3%), harpagide, 8-p-coumaroylharpagide, 8-feruloylharpagide, 8-cinnamylmyoporoside, 60-O-p-coumaroylharpagide, 60-p-coumaroylprocumbide, and pagoside.(3–5) p-Coumaroyl esters occur as E and Z isomers.(5)

Phenylpropanoids Acteoside and isoacteoside, 6-O-acetylacteoside,( 4–6) 2,6-O-diacetylacteoside.(7)

Other Constituents Amino acids, flavonoids (e.g. kaempferol, luteolin), triterpenoids, sterols.(4, G75)

Other Plant Parts The flower, stem and ripe fruit are reported to be devoid of harpagoside; the leaf contains traces of iridoids.(8)

 

Quality Of Plant Material and Commercial Products

According to the British and European Pharmacopoeias, devil's claw root consists of the cut and dried tuberous secondary roots of H. procumbens DC. It contains not less than 1.2% of harpagoside, calculated with reference to the dried drug.(G81, G84) As with other herbal medicinal products, there is variation in the qualitative and quantitative composition of commercial devil's claw root preparations.

Some commercial extracts of devil's claw root may have been prepared not only from the roots of H. procumbens, but also from the roots of H. zeyheri, which are similar macroscopically.(9) However, the two species differ in the concentration of the constituents harpagoside and 8-p-coumaroylharpagide. On this basis it has been stated that the species can be distinguished chemically by determining the ratio harpagoside : 8-p-coumaroylharpagide.

The ratio is stated to be near one for H. zeyheri and between 20 and 38 for H. procumbens which has a low 8-pcoumaroylharpagide content.(9) While this ratio may be sufficient for chemotaxonomic differentiation, it may not be adequate for quality control.(10)

Other studies have demonstrated that the harpagoside content of several powdered dry extracts of devil's claw from different manufacturers varies, and that each extract has a unique profile of other constituents.(11) The harpagoside content of commercial extracts of H. procumbens has been reported to range from 0.8– 2.3%.(12)

 

COMPOUNDS

Liridoide monoterpenes: including harpagoside (extremely bitter), harpagide, procumbide

Phenylethanol derivatives: including acteoside (verbascoside); isoacteoside

Oligosaccharides: stachyose

Harpagoquinones (traces)

 

CHEMICAL COMPONENTS

The major active constituent is considered to be the bitter iridoid glucoside, harpagoside, which should constitute not less than 1.2% of the dried herb. Other iridoid glycosides include harpagide, procumbide, 8-O-(p-coumaroyl)-harpagide and verbascoside. About 50% of the herb consists of sugars. There are also triterpenes, phytosterols, plant phenolic acids, flavonol glycosides and phenolic glycosides. Harpagophytum zeyheri, which has a lower level of active compounds, may be partially substituted for H. procumbens in some commercial preparations (Stewart & Cole 2005).

The extraction solvent (e.g. water, ethanol) has a major impact on the active principle of the products (Chrubasik 2004a). When administering H. procumbens extract topically it was found that higher penetration of all compounds occurred from an ethanol/water preparation (Abdelouahab & Heard 2008b).

 

USES

USES

Devil’s claw is used to increase the appetite and to treat joint pain and infl ammation, arthritis, allergies, headache, heartburn, dysmenorrhea, gastrointestinal upset, malaria, gout, and nicotine poisoning.

 

FOOD USE

Devil's claw is not used in foods.

 

HERBAL USE

Devil's claw is stated to possess anti-inflammatory, antirheumatic, analgesic, sedative and diuretic properties. Traditionally, it has been used as a stomachic and a bitter tonic, and for arthritis, gout, myalgia, fibrositis, lumbago, pleurodynia and rheumatic disease.(G2, G6–G8,G32, G64) Modern use of devil's claw is focused on its use in the treatment of rheumatic and arthritic conditions, and low back pain.

 

CLINICAL USE

Arthritis

Overall, evidence from clinical trials suggests that devil’s claw is effective in the treatment of arthritis. An observational study of 6 months’ use of 3–9 g/day of an aqueous extract of devil’s claw root reported significant benefit in 42–85% of the 630 people suffering from various arthritic complaints (Bone & Walker 1997). In a 12-week uncontrolled multicentre study of 75 patients with arthrosis of the hip or knee, a strong reduction in pain and the symptoms of osteoarthritis were observed in patients taking 2400 mg of devil’s claw extract daily, corresponding to 50 mg harpagoside (Wegener & Lupke 2003). Similar results were reported in a 2-month observational study of 227 people with osteoarthritic knee and hip pain and non-specific low back pain (Chrubasik et al 2002) and a double-blind study of 89 subjects with rheumatic complaints using powdered devil’s claw root (2 g/day) for 2 months, which also provided significant pain relief, whereas another double-blind study of 100 people reported benefit after 1 month (Bone & Walker 1997).

A case report suggests that devil’s claw relieved strong joint pain in a patient with Crohn’s disease (Kaszkin et al 2004b). A single group open study of 8 weeks duration involving 259 patients showed statistically significant improvements in patient assessment of global pain, stiffness and function, and significant reductions in mean pain scores for hand, wrist, elbow, shoulder, hip, knee and back pain. Moreover, quality of life scores significantly increased and 60% of patients either reduced or stopped concomitant pain medication (Warnock et al 2007).

Comparisons with standard treatment have also been investigated. In 2000, encouraging results of a randomised double-blind study comparing the effects of treatment with devil’s claw 2610 mg/day with diacerhein 100 mg/day were published (Leblan et al 2000). The study involved 122 people with osteoarthritis of the hip and/or knee and was conducted over 4 months. It found that both treatment groups showed similar considerable improvements in symptoms of osteoarthritis; however, those receiving devil’s claw required fewer rescue analgesics. One double-blind, randomised, multicentre clinical study of 122 patients with osteoarthritis of the knee and hip found that treatment with Harpadol (6 capsules/day, each containing 435 mg of cryoground powder of H. procumbens) given over 4 months was as effective as diacerhein (an analgesic) 100 mg/day (Chantre et al 2000). However, at the end of the study, patients taking Harpadol were using significantly fewer NSAIDs and had a significantly lower frequency of adverse events. In a 6-week study of only 13 subjects, similar benefits for devil’s claw and indomethacin were reported (Newall et al 1996). A preliminary study comparing the proprietary extract Doloteffin with the COX-2 inhibitor rofecoxib reported a benefit with the herbal treatment but suggested that larger studies are still required (Chrubasik et al 2003b). Previously reviews have concluded that there is moderate evidence of the effectiveness of H. procumbens in the treatment of osteoarthritis of the spine, hip and knee; however it is suggested, as with many herbal medicines, that evidence of effectiveness is not transferable from product to product and that the evidence is more robust for products that contain at least 50 mg of harpagoside in the daily dosage (Chrubasik et al 2003a, Gagnier et al 2004, Long et al 2001).

Recently two reviews have concluded that ‘data from higher quality studies suggest that Devil’s claw appeared effective in the reduction of the main clinical symptom of pain’ (Brien et al 2006) and that the evidence of effectiveness was ‘strong’ for at least 50 mg of harpagoside as the daily dose (Chrubasik JE et al 2007). Nevertheless, 2 other recent reviews concluded that there was only ‘limited evidence’ (Ameye & Chee 2006) and ‘insufficient reliable evidence’ regarding the long term effectiveness of devil’s claw (Gregory et al 2008).

The herb is Commission E approved as supportive therapy for degenerative musculoskeletal disorders (Blumenthal et al 2000) and ESCOP approved for painful osteoarthritis (ESCOP 2003).

 

Back pain

Several double-blind studies have reported benefit with devil’s claw in people with back pain. A doubleblind study of 117 people with back pain reported decreased pain and improved mobility after 8 weeks’ treatment with devil’s claw extract LI 174, known commercially as Rivoltan (Laudahn & Walper 2001).

Use of the same extract provided significant pain relief after 4 weeks in another randomised, doubleblind placebo-controlled study of 63 subjects with muscle stiffness (Gobel et al 2001). Similar results were reported in two double-blind studies of 118 people (Chrubasik et al 1996) and 197 people (Chrubasik et al 1999) with chronic lower back pain.

Devil’s claw appears to compare favourably to conventional treatments. A 6-week double-blind study of 88 subjects comparing devil’s claw to rofecoxib found equal improvements in both groups (Chrubasik et al 2003b) A follow-up of the subjects from that study who were all given devil’s claw for 1 year found that it was well tolerated and improvements were sustained (Chrubasik et al 2005). In an open, prospective study, an unspecific lower back pain treatment with Harpagophytum extract and conventional therapy were found to be equally effective (Schmidt et al 2005).

Three recent reviews looking at the treatment of low back pain concluded that there is strong evidence for short-term improvements in pain and rescue medication for devil’s claw products standardised to 50 and 100 mg harpagoside as daily doses (Chrubasik JE et al 2007, Gagnier et al 2006, 2007). Devil’s claw root is approved for relief of low back pain by ESCOP (ESCOP 2003).

 

Dyspepsia

Traditionally, devil’s claw has also been used to treat dyspepsia and to stimulate appetite (Fisher & Painter 1996). The bitter principles in the herb provide a theoretical basis for its use in these conditions, although controlled studies are not available to determine effectiveness. The herb is Commission E (Blumenthal et al 2000) and ESCOP (2003) approved for dyspepsia and loss of appetite.

 

OTHER USES

Traditionally, the herb is also used internally to treat febrile illnesses, allergic reactions and to induce sedation, and topically for wounds, ulcers, boils and pain relief (Fisher & Painter 1996, Mills & Bone 2000), as well as for diabetes, hypertension, indigestion and anorexia (Van Wyk 2000).

 

 

Figure 1. Devil’s claw (Harpagophytum procumbens).

 

Figure 2. Devil’s claw – dried drug substance (root).

 

ACTIONS

Antiinflammatory Action

Several studies have evaluated the antiinfl ammatory properties of devil’s claw in the treatment of joint conditions. The results are mixed. One Canadian study (Whitehouse et al, 1983) evaluated Harpagophytum procumbens for reduction of rat hindfoot edema. Devil’s claw was completely ineffective, even at doses greater than 100 times the recommended human dose. Another study produced similar results. No clinical signifi cance was found when human subjects consumed devil’s claw (Moussard et al, 1992). Another study (Baghdikian et al, 1997) reported confl icting results on harpagoside, one of the chemical components of the herb, which showed analgesic and antiinfl ammatory properties. H. procumbens was found to produce analgesic and antiinfl ammatory effects (Chantre et al, 2000; Fiebich et al, 2001; Gobel et al, 2000).

Another study determined that the iridoid glycosides are responsible for the analgesic, antiinfl ammatory, and antiphlogistic effects of devil’s claw (Wegener, 1999). Devil’s claw possesses analgesic, antiinfl ammatory, and hypoglycemic properties as suggested in folklore (Mahomed, 2004).

 

Cardiovascular Action

When rats and rabbits were studied to determine the cardiovascular effects of H. procumbens, a signifi cant dose-dependent reduction occurred in arterial blood pressure, along with a reduction in heart rate at high doses. Harpagoside, one of the chemical components of the herb, exhibited less activity than did the extract of H. procumbens.

The extract of H. procumbens produced a mild decrease in heart rate, with mild positive inotropic effects at low doses but a signifi cant negative inotropic effect at higher doses. Harpagoside showed negative chronotropic and positive inotropic effects (Circosta et al, 1984). Another study demonstrated that devil’s claw exerts a protective action in hyperkinetic ventricular arrhythmias in rats (Costa De Pasquale et al, 1985).

 

Other Actions

Devil’s claw depresses the central nervous system and may be used as an anticoagulant as described in folklore (Mahomed, 2006).

 

PHARMACOLOGICAL ACTIONS

The active constituents of devil's claw are widely held to be the iridoid glucosides although, of these, it has not been definitively established whether harpagoside is the most important pharmacologically active constituent of the whole extract. Other compounds present in the root may contribute to the pharmacological activities of devil's claw.(15, 16) It has also been suggested that harpagogenin, formed by in vivo acid hydrolysis of harpagoside, may have biological activity.(17)

 

IN VITRO AND ANIMAL STUDIES

Pharmacokinetics   Transformation of the iridoids harpagide, harpagoside and 8-O-(p-coumaroyl)-harpagide into the pyridine monoterpene alkaloid aucubinine B, chemically or by human intestinal bacteria in vitro, has been documented.(18, 19) However, it is not known if aucubinine B is formed in vivo by intestinal bacteria and, therefore, whether it contributes to the pharmacological activity of devil's claw.(19)

 

Anti-inflammatory and analgesic activities   Animal studies of the anti-inflammatory and analgesic activities of devil's claw have reported conflicting results. Activity appears to differ depending on the route of administration of devil's claw, and the model of inflammation, whether acute or subacute. Also, studies have assessed the effects of different preparations of H. procumbens (e.g. aqueous extracts and ethanolic extracts) and it is important to consider this when interpreting the results.

In controlled experiments in rats, a 60% ethanol extract of H. procumbens roots injected (compartment and site not specified) at doses of 25, 50 and 100 mg/kg body weight daily for four days beginning five days after sub-plantar injection of Freund's adjuvant produced a significantly greater antinociceptive response in the hot-plate test and significantly reduced paw oedema than did control (distilled water) on days 6–8 after induction of experimental arthritis (p < 0.01 for all).(20) Similar results were obtained when administration of H. procumbens extract was initiated 20 days after sub-plantar injection of Freund's adjuvant and continued for 20 days, with tests for antinociceptive and antiinflammatory activity performed on four occasions during this period. Pretreatment with a dried aqueous extract of devil's claw root at doses of 100 mg/kg and above, administered intraperitoneally, resulted in peripheral analgesic activity demonstrated by a significant reduction in the number of writhings induced by acetic acid in mice.(16) However, no effect was observed in the hotplate test, indicating a lack of central analgesic activity with devil's claw extract.

The peripheral analgesic properties of intraperitoneal dried aqueous extract of devil's claw have been confirmed in other studies for doses of 400 mg/kg and above.(9) A subsequent series of experiments found that administration of an aqueous extract of H. procumbens root at doses of 200–800 mg/kg body weight intraperitoneally resulted in significantly greater antinociceptive effects than did control in both the hot-plate and acetic-acid induced writhings tests in mice (p < 0.05 versus control) and, at a dose of 400 or 800 mg/kg body weight, in a significant reduction in egg-albumin induced hind-paw inflammation in rats, compared with control (p < 0.05).(21)

In contrast, other studies have reported that dried aqueous extract of devil's claw administered orally had no effect on carrageenan- or Mycobacterium butyricum- (Freund's adjuvant) induced oedema in rat paw, whereas both indometacin and aspirin displayed significant anti-inflammatory activity.(22, 23) However, dried aqueous extract of devil's claw administered by intraperitoneal injection demonstrated significant activity in the carrageenan- induced oedema test in rats, an acute model of inflammation.(16) The effect on oedema was dose-dependent for doses of devil's claw extract 100–400 mg/kg, and reached a maximum three hours after carrageenan injection. Other studies in rats have reported significant reductions in oedema using the same model following pretreatment with intraperitoneal(9, 24) and intraduodenal, but not oral, dried aqueous extract of devil's claw.(24)

Anti-inflammatory activity of harpagoside has been demonstrated in experimental models, including the croton oil-induced granuloma pouch test, and for harpagogenin, the aglucone of harpagoside, in the croton oil-induced granuloma pouch test and in formalin-induced arthritis in rats.(25) Studies have also reported peripheral analgesic and antiinflammatory properties for the related species Harpogophytum zeyheri.(9) Animal studies using aqueous extracts of devil's claw have suggested that the extract may be inactivated by passage through the acid environment of the stomach.(16, 24) One study compared the anti-inflammatory activities of aqueous devil's claw extract administered by different routes. Intraperitoneal and intraduodenal administration led to a significant reduction in the carrageenan-induced rat paw oedema test, but there was no effect following oral administration.(24) In another study, aqueous devil's claw extract pretreated with hydrochloric acid to mimic acid conditions in the stomach showed no activity in pharmacological models of pain and inflammation.(16)

A clear mechanism of action for the purported anti-inflammatory effects of devil's claw has yet to be established. In vitro, devil's claw (100 mg/mL ) had no significant effect on prostaglandin (PG) synthetase activity, whereas indometacin (316 mg/mL ) and aspirin (437 mg/mL ) caused 50% inhibition of this enzyme.(23) In other in vitro studies in human whole blood samples, devil's claw extracts and fractions of extracts were tested for their effects on thromboxane B2 (TXB2) and leukotriene (LT) biosynthesis.(26) TXB2 is an end-product of arachidonic acid metabolism by the cyclooxygenase 1 (COX-1) pathway. Inhibition appeared to be dependent on the harpagoside content of the extracts or fractions.(26) An aqueous extract of H. procumbens inhibited lipopolysaccharide-induced enhancement of cyclooxygenase-2 activity, resulting in suppression of PGE2 synthesis in in-vitro experiments using the mouse fibroblast cell line L929.(27) In the same system, the extract inhibited inducible nitric oxide synthase (iNOS) mRNA expression, resulting in suppression of nitric oxide production. Inhibition of iNOS expression by an aqueous extract of H. procumbens roots, resulting in suppression of nitrite production, has also been described following experiments in rat renal mesangial cells. The effect was observed with a harpagoside free extract and with an extract containing a high concentration (27%) of harpagoside, but not with extracts containing around 2% harpagoside, indicating that high concentrations of harpagoside as well as other concentrations are necessary to bring about the effect.(28)

Harpagoside (100 mmol/L), but not harpagide (100 mmol/L), inhibited calcium ionophore A23187-stimulated release of TXB2 from human platelets.(29) However, harpagoside and harpagide had no significant inhibitory effect on calcium ionophore A23187-stimulated release of PGE2 and LTC4 from mouse peritoneal macrophages.(29)

Other preclinical studies have described effects for devil's claw extracts and/or isolated constituents on other pathways involved in inflammatory processes. In vitro inhibition of tumour-necrosisfactor- a (TNF-a) synthesis in lipopolysaccharide-stimulated human monocytes by a hydroalcoholic extract of devil's claw (SteiHap 69) has also been documented.(30) Inhibitory activity against human leukocyte elastase (a serine proteinase involved in inflammatory processes) has been reported for an aqueous extract of H. procumbens roots (drug to extract ratio 1.5-2.5 : 1) and the isolated constituents 60-O-acetylacteoside, isoacteoside, 8-p-coumaroylharpagide, pagoside and caffeic acid, with IC50 values of 542, 47, 179, 179, 154 and 86 mg/mL , respectively. The IC50 values for several other constituents, including acteoside and harpagoside were higher than 300 mg/mL  (4). An ethanol extract of H. procumbens significantly reduced IL-1b-induced production of several matrix metalloproteinase enzymes (MMPs) in human chondrocytes.(31) (In inflammatory diseases, there is increased production of cytokines such as IL-1b and TNF-a, which results in an increased production of MMPs which breakdown the extracellular cartilage matrix.)

 

Other activities Crude methanolic extracts of devil's claw have been shown to be cardioactive in vitro and in vivo in animals. A protective action against ventricular arrhythmias induced by aconitine, calcium chloride and epinephrine (adrenaline)/chloroform has been reported for devil's claw given intraperitoneally or added to the reperfusion medium.(32, 33) The crude extract was found to exhibit greater activity than pure harpagoside.(33) In isolated rabbit heart, low concentrations of a crude methanolic extract had mild negative chronotropic and positive inotropic effects,(32) whereas high concentrations caused a marked negative inotropic effect with reduction in coronary blood flow.(32) In anaesthetised dogs, harpagoside administered orally by gavage caused a decrease in mean aortic pressure and arterial and pulmonary capillary pressure.(34)

In vitro, harpagoside has been shown to decrease the contractile response of smooth muscle to acetylcholine and barium chloride on guinea-pig ileum and rabbit jejunum. Harpagide was found to increase this response at lower concentrations, but antagonised it at higher concentrations.(35) On the basis of these studies in isolated smooth muscle, it was suggested that the constituents of devil's claw may influence mechanisms regulating calcium influx.(35)

Methanolic extracts have also exhibited hypotensive properties in normotensive rats, causing a decrease in arterial blood pressure following oral doses of 300 mg/kg and 400 mg/kg body weight.(32) Aqueous fractions derived from an extract of devil's claw root (drug to extract ratio 2 : 1 containing 2.6% harpagoside) showed antioxidant activity in an in-vitro assay based on ability to scavenge 2,20-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)-derived radicals.(36) However, harpagoside showed only weak antioxidant activity. In mice, a methanol extract of H. Procumbens root tubers applied topically to shaven skin 30 minutes before application of 12-O-tetradecanoylphorbol-13-acetate (TPA), a stimulator of COX-2 expression, led to a significant reduction in COX-2 protein when assessed four hours after TPA administration.(37) The extract did not have any effect on TPA-induced activation of nuclear factor-kB, but inhibited TPA-induced activation of activator protein-1, which is involved in the regulation of COX-2 in mouse skin. Overexpression of COX-2 is thought to be involved in tumour promotion. Antidiabetic activity has been described for an aqueous extract of H. procumbens root in in vivo experiments in rats with streptozotocin-induced diabetes mellitus.(21) The extract significantly reduced blood glucose concentrations in both fasted normoglycaemic rats and fasted diabetic rats when administered intraperitoneally at doses of 800 mg/kg body weight. T

wo diterpene constituents ((þ)-8,11,13-totaratriene-12,13-diol and (þ)-8,11,13-abietatrien-12-ol) isolated using bioassay-guided fractionation from a petroleum ether extract of H. procumbens root were found to be active against a chloroquine-sensitive (D10) and a chloroquine-resistant (K1) strain of Plasmodium falciparum in vitro (IC50 < 1 mg/mL ).(2)Devil's claw extracts possess weak antifungal activity against Penicillium digitatum and Botrytis cinerea.(38)

 

CLINICAL STUDIES

Pharmacokinetics There is little published information on the pharmacokinetics of devil's claw extracts in humans. A pharmacokinetic study involving a small number of healthy male volunteers (n = 3) measured plasma harpagoside concentrations after oral administration of devil's claw extract (WS1531 containing 9% harpagoside) 600, 1200 and 1800 mg as film-coated tablets.(26) Maximal plasma concentrations of harpagoside were reached after 1.3–1.8 hours, and were 8.2 ng/mL  and 27.8 ng/mL  for doses of harpagoside of 108 and 162 mg, respectively (corresponding to 1200 and 1800 mg devil's claw extract, respectively). Other studies involving small numbers of healthy male volunteers indicated that the half-life ranged between 3.7 and 6.4 hours. Other results suggested that there may be low oral absorption or a considerable first-pass effect with devil's claw extract, although this needs further investigation.(26)

Pharmacodynamics A study involving healthy volunteers investigated the effects on eicosanoid production of orally administered devil's claw (four 500-mg capsules of powder, containing 3% glucoiridoids, daily for 21 days).(39) No statistically significant differences on PGE2, TXB2, 6-keto-PGF1a and LTB4 were observed following the period of devil's claw administration, compared with baseline values. By contrast, in a subsequent study involving whole blood samples taken from healthy male volunteers, a biphasic decrease in basal cysteinyl-leukotriene (Cys-LT) biosynthesis, compared with baseline values, was observed following oral administration of devil's claw extract (WS1531 containing 9% harpagoside) 600, 1200 and 1800 mg as film-coated tablets.(26)

Therapeutic activity The efficacy and effectiveness of devil's claw have been investigated in around 20 clinical studies involving patients with rheumatic and arthritic conditions, and low back pain.(15, 40) These studies have involved different methodological designs, including several uncontrolled studies, and different preparations of devil's claw, including crude drug and aqueous extracts. Evaluating the evidence is further complicated as preparations tested in clinical trials typically have been standar-dised for their harpagoside content and, although harpagoside is believed to contribute to activity, it is not yet clear to what extent and which other constituents are important. Therefore, at present, there is insufficient evidence to draw definitive conclusions regarding the efficacy of specific devil's claw preparations, and because of the differences in the pharmaceutical quality of individual preparations, general conclusions on efficacy cannot be drawn.(41)

A systematic review of the quality of clinical trials involving devil's claw found that although the results of some studies have provided evidence for the effectiveness of certain devil's claw preparations, the quality of evidence was not sufficient to support the use of any of the available products.(42)

A systematic review of 12 controlled, randomised or quasirandomised trials of H. procumbens preparations in patients with osteoarthritis (5 trials), low back pain (4 trials) and mixed pain conditions (3 trials) found differing levels of evidence for the different H. procumbens preparations assessed. There was evidence (from two trials involving a total of 325 participants) that an aqueous extract of H. procumbens administered orally at a dose equivalent to harpagoside 50 mg daily for four weeks was superior to placebo in reducing pain in patients with acute episodes of chronic non-specific low-back pain.(13) There was also evidence (from one trial for each) that the same extract administered orally at a dose equivalent to harpagoside 100 mg daily for four weeks was superior to placebo, and at a dose

equivalent to harpagoside 60 mg daily for six weeks was not inferior to rofecoxib 12.5 mg daily, in reducing pain in patients with acute episodes of chronic non-specific low-back pain. There was evidence that powdered H. procumbens plant material at a dose equivalent to 57 mg harpagoside daily for 16 weeks was not inferior to diacerhein. Overall, however, the limited amount of data and heterogeneous nature of the available studies, indicate that further randomised controlled trials assessing well-characterised H. procumbens preparations and involving sufficient numbers of patients are required. Several of the trials mentioned above are discussed in more detail below. A randomised, double-blind, placebo-controlled study involving 118 patients with acute exacerbations of chronic low back pain investigated the effects of devil's claw extract 800 mg three times daily (equivalent to 50 mg harpagoside daily) for four weeks.(43) There was no statistically significant difference between the devil's claw and placebo groups in the primary outcome measure –consumption of the opioid analgesic tramadol over weeks 2–4 of the study – among the 109 patients who completed the study. This was an unusual choice of primary outcome measure as it gives no direct indication of the degree of pain experienced by participants. There was a trend towards improvement in a modified version of the Arhus Low Back Pain Index (a measure of pain, disability and physical impairment) for devil's claw recipients compared with placebo recipients, although this did not reach statistical significance. A greater proportion of patients in the devil's claw group were pain-free at the end of the study, although this was only a secondary outcome measure.

On the basis of these findings, a subsequent randomised, double-blind, placebo-controlled trial involving 197 patients with exacerbations of low back pain tested the effects of two doses of devil's claw (WS1531) extract against placebo.(44) Participants received devil's claw extract 600 mg or 1200 mg daily (equivalent to 50 mg and 100 mg harpagoside daily, respectively), or placebo, for four weeks. There was a statistically significant difference (p =0.027) between devil's claw and placebo with respect to the primary outcome measure – the number of patients who were pain-free without tramadol for at least five days during the last week of the study. However, numbers of patients who were painfree were low (3, 6 and 10 for placebo, devil's claw 600 mg daily and devil's claw 1200 mg daily, respectively). Furthermore, this is a non-standard outcome measure. Arhus Low Back Pain Index scores improved significantly in all three groups, compared with baseline values, although there was no statistically significant difference between groups.

In a randomised, double-blind, placebo-controlled study involving patients with non-specific low back pain, 65 participants received devil's claw extract (LI-174, Rivoltan), or placebo, 480 mg twice daily (equivalent to 24 mg harpagoside daily) for four weeks.(45) There was a significant improvement (p < 0.001) in visual analogue scale (VAS) scores for muscle pain in the devil's claw group, but not the placebo group, compared with baseline values, after two and four weeks' treatment. Differences in VAS scores between the two groups were statistically significant after four weeks' treatment (p < 0.001). Significant differences between the two groups in favour of devil's claw after four weeks' treatment were also observed with several other parameters, including muscle stiffness and muscular ischaemic pain.

A small number of studies has compared the efficacy of devil's claw with that of conventional pharmaceutical agents in the treatment of low back pain. In a randomised, double-blind, pilot trial, 88 participants with acute exacerbations of low back pain received an aqueous extract of devil's claw (Doloteffin; drug to extract ratio 1.5-2.5:1) 2400 mg daily in three divided doses (equivalent to 60 mg harpagoside daily), or rofecoxib (Vioxx) 12.5 mg daily for six weeks.(46) At the end of this period, compared with baseline values, there were improvements in Arhus Low Back Pain Index scores, health assessment questionnaire scores, and increases in the numbers of pain-free patients for both groups. There were no statistically significant differences between groups for any of the outcome measures but, because the study did not include sufficient numbers of patients, these findings do not demonstrate clinical equivalence between the two treatments.(46)

A randomised, double-blind, pilot trial in which 88 participants with acute exacerbations of low back pain received an aqueous extract of devil's claw (Doloteffin), or rofecoxib (Vioxx) for six weeks offered participants continuing treatment with devil's claw aqueous extract two tablets three times daily for up to one year after the six-week pilot study. Participants were not aware of their initial study group (i.e. devil's claw extract or rofecoxib) until towards the end of the one-year follow-up study.(47) In total, 38 and 35 participants who had previously received devil's claw and rofecoxib, respectively, participated in the follow-up study, and underwent assessment every six weeks. After 24 and 54 weeks, 53 and 43 participants, respectively, remained in the study. There were no convincing differences between the two groups (i.e. those who previously received devil's claw and those who received rofecoxib) with respect to pain scores, use of additional analgesic medication, Arhus Index scores and health assessment questionnaire scores.

Furthermore, the uncontrolled design of the follow-up study would have precluded any definitive conclusions regarding differences between the two groups. A randomised, double-blind trial compared the efficacy of devil's claw extract with that of diacerein in 122 patients with osteoarthritis of the knee and hip.(14) Participants received powdered cryoground devil's claw (Harpadol) 2.61 g daily, or diacerein 100 mg daily, for four months.

VAS scores for spontaneous pains improved significantly in both groups, compared with baseline values, and there were no differences between devil's claw and diacerein with respect to VAS scores. In a placebo-controlled study involving 89 patients with rheumatic complaints, devil's claw recipients (who received powdered crude drug 2 g daily for two months) showed significant improvements in sensitivity to pain and in motility (as measured by the finger-to-floor distance), compared with placebo recipients.(48)

Several, open, uncontrolled, post-marketing surveillance studies( 49–53) have assessed the effects of devil's claw preparations in patients with rheumatic and arthritic disorders, and back pain. These studies typically have reported improvements in pain scores at the end of the treatment period, compared with baseline values. However, the design of these studies (i.e. no control group) does not allow any conclusions to be drawn on the effects of devil's claw in these conditions as there are alternative explanations for the observed effects.

Another study involved 45 patients with osteo- or rheumatoid arthritis who received devil's claw root extract 2.46 g daily for two weeks in addition to non-steroidal anti-inflammatory drug (NSAID) treatment, followed by devil's claw extract alone, for four weeks.(54) It was reported that there were no statistically significant changes in pain intensity and duration of morning stiffness during the period of treatment with devil's claw extract alone. In subgroups of patients with rheumatoid arthritis and those with osteoarthritis, small decreases were observed in concentrations of C-reactive protein and creatinine, respectively.

The design of this study in terms of the treatment regimen (NSAID followed by devil's claw extract without a wash-out period), also precludes definitive conclusions about the effects of devil's claw preparations.

 

MAIN ACTIONS

Anti-inflammatory/Analgesic

There is good in vitro and in vivo pharmacological evidence of the anti-inflammatory and analgesic properties of devil’s claw, although some negative findings have also been reported (McGregor et al 2005). Overall, greatest activity appears to be in semi-chronic rather than acute conditions. Devil’s claw exerted significant analgesic effects against thermally and chemically induced nociceptive pain stimuli in mice and significant dose-related reduction of experimentally induced acute inflammation in rats (Mahomed & Ojewole 2004), as well as reducing pain and inflammation in Freund’s adjuvant- induced arthritis in rats (Andersen et al 2004). Results from a recent study in mice suggest that the opioid system is involved in the antinociceptive effects of H. procumbens extract (Uchida et al 2008).

The iridoids, particularly harpagoside, are thought to be the main active constituents responsible for the anti-inflammatory activity, although the mechanism of action is unknown and devil’s claw is also rich in water-soluble antioxidants (Betancor- Fernandez et al 2003). More recent in vitro evidence suggests that the anti-inflammatory effect may in part be due to antioxidant activity (Denner 2007, Grant et al 2009, Langmead et al 2002).

A study administering H. procumbens extract intraperitoneally to rats found that the anti-inflammatory response does not depend on the release of adrenal corticosteroids (Catelan et al 2006). Contradictory evidence exists as to whether devil’s claw affects prostaglandin (PG) synthesis. Early in vitro and in vivo studies suggest that it does not inhibit PG synthesis (Whitehouse et al 1983) and this is supported by studies of PG production in humans (Moussard et al 1992). However, more recent investigations have suggested that its anti-inflammatory and analgesic activities are due to suppression of PGE2 synthesis and nitric oxide production and that the herb may suppress expressions of COX-2 and iNOS (Jang et al 2003). Harpagoside alone has been shown to suppress COX-2 and iNOS at both the mRNA and protein level in vitro due to a suppression of NF-kappaB activation (Huang et al 2006).

Recent in vitro research shows that harpagoside and 8-O-(p-coumaroyl)-harpagide exhibit a greater reduction in COX-2 expression than verbascoside and that harpagide on the other hand causes a significant increase in COX-2 expression (Abdelouahab & Heard 2008a). Additionally, methanolic extracts of devil’s claw have been shown to inhibit COX-2 in vivo (Kundu et al 2005, Na et al 2004). Inhibition of leukotriene synthesis has been observed in vitro, which appears to relate to the amount of harpagoside present (Loew et al 2001).

A study using subcritical and supercritical CO2 extracts (15 to 30% harpagoside) showed almost total inhibition of 5-lipoxygenase biosynthesis at 51.8 mg/mL  of extract, whereas the conventional extract (2.3% harpagoside) did not inhibit the enzyme significantly (Gunther et al 2006).

In vivo experiments have determined that the method of administration of devil’s claw affects its anti-inflammatory properties. Intraperitoneal and intraduodenal administration was shown to reduce carrageenan-induced oedema, whereas oral administration had no effect, suggesting that exposure to stomach acid may reduce its anti-inflammatory activity (Soulimani et al 1994). This is supported by a study that found a loss of anti-inflammatory activity after acid treatment (Bone & Walker 1997). devil’s claw may be used as an anti-inflammatory agent in the treatment of glomerular inflammatory diseases (Kaszkin et al 2004a). Devil’s claw extract produced a concentration-dependent suppression of nitrite formation in rat mesangial cells in vitro due to an inhibition of iNOS expression through interference with the transcriptional activation of iNOS. It was found that this activity was due to harpagoside, together with other constituents that possibly have strong anti-oxidant activity (Kaszkin et al 2004b). It has been suggested that the suppression of inflammatory cytokine synthesis, demonstrated in vitro and vivo (Fiebich et al 2001, Spelman et al 2006), could explain its therapeutic effect in arthritic inflammation (Kundu et al 2005). Fiebich and co-workers found that a 60% ethanolic extract decreases the expression of IL-1-beta, IL-6, and TNF-alpha (Fiebich et al 2001).

 

Chondroprotective

In vitro data suggest that the active principles of H. procumbens inhibit not only inflammatory mediators but also mediators of cartilage destruction, such as matrix metalloproteinases, NO and elastase (Boje et al 2003, Schulze-Tanzil et al 2004). A study using an animal model confirmed a chondroprotective effect in which the tissue inhibitor of metalloproteinase- 2 is involved (Chrubasik et al 2006).

 

Hypoglycaemic

Devil’s claw extract produced a dose-dependent, significant reduction in the blood glucose concentrations of both fasted normal and fasted diabetic rats (Mahomed & Ojewole 2004).

 

OTHER ACTIONS

In vitro and in vivo evidence suggests that harpagoside may exhibit cardiac affects and lower blood pressure, heart rate and reduce arrhythmias (Fetrow & Avila 1999). As an extremely bitter herb, devil’s claw is thought to increase appetite and bile production. Diterpenes extracted from the roots and seeds of devil’s claw exhibited selective antiplasmodial (Clarkson et al 2003) and antibacterial activity (Weckesser et al 2007) in vitro, which may have future relevance in view of the increasing resistance to conventional antimalarials and antibiotics. One study showed that aqueous devil’s claw extract can markedly delay the onset, as well as reduce the average duration, of convulsion in mice. Although not conclusive, it seems that the extract produces its anticonvulsant activity by enhancing GABAergic neurotransmission and/or facilitating GABAergic action in the brain (Mahomed & Ojewole 2006).

 

ACTIVITIES

Allergenic (f; PHR); Analgesic (2; CAN; KOM; MAB; PH2); Antiarrhythmic (1; APA); Antiarthritic (1; CRC; MAB; PH2; VVG); Antiedemic (1; BGB); Antiexudative (f; SHT); Antiinflammatory (2; APA; BGB; CRC; KOM; PH2); Antipyretic (f; HHB); Antirheumatic (1; CAN; MAB); Aperitif (2; APA; HH2; KOM; VAG); Bitter (1; APA; MAB; PED); Choleretic (2; HH2; KOM; PH2); Depurative (f; BGB; PED); Digestive (f; SKY); Diuretic (f; CAN); Hypocholesterolemic (1; CRC; PED; VAG); Hypotensive (1; APA; BGB); Hypouricemic (1; CRC; PED; VAG); Laxative (f; MAB; WBB); Secretagogue (1; PH2); Sedative (f; CAN); Tonic (1; APA; MAB; VVG); Uricolytic (1; APA); Uterocontractant (f; VAG).

 

INDICATIONS

Aging (f; CRC); Allergy (1; BGB; CRC; MAB; PH2); Anorexia (2; APA; HH2; KOM; PH2; SHT; VAG); Arrhythmia (1; APA; BGB; MAB); Arthrosis (2; APA; CRC; KOM; MAB; PH2; VVG); Atherosclerosis (f; CRC); Backache (2; BGB; BRU; MAB; PHR); Blood (f; BGB); Boil (1; BGB; CRC; MAB; VVG); Bursitis (f; WAF); Cancer (f; APA; WBB); Cancer, skin (f; CRC); Cardiopathy (1; MAB); Childbirth (1; APA; BRU; CRC; MAB; VAG; WBB); Cholecystosis (2; CRC; PHR; PH2); CNS (f; PH2); Cramp (f; VAG); Cystosis (f; CRC; HHB; PH2); Dermatosis (f; BGB; PHR); Diabetes (f; CRC; HHB; VAG); Dysmenorrhea (1; CRC; VAG); Dyspepsia (2; APA; BGB; CRC; KOM; PH2; SHT); Edema (1; BGB); Enterosis (f; BRU; CRC); Fever (1; APA; BGB; BRU; HHB; VAG); Fibromyalgia (f; WAF); Fibrosis (1; CAN; VAG); Gastrosis (f; BRU; CRC); Gout (1; CAN; CRC; VAG); Headache (1; APA; BGB; MAB); Heartburn (2; CRC; KOM; SKY); Hepatosis (2; CRC; PHR; PH2); High Blood Pressure (1; APA; BGB; VAG); High Cholesterol (1; CRC; PED; VAG); Inflammation (2; APA; BGB; CRC; KOM; MAB; PH2); Insomnia (f; CAN); Lumbago (1; BGB; CAN; CRC); Migraine (1; MAB); Myalgia (f; CAN); Nephrosis (f; CRC; HHB; PH2); Nervousness (f; CAN); Neuralgia (1; BGB; CRC); Neurosis (f; PH2); Osteoarthrosis (1; VAG); Pain (2; APA; BGB; CAN; KOM; MAB; PHR; PH2; VVG); Parturition (f; VVG); Pleurodynia (f; CAN); Pregnancy (f; APA; PH2); Rheumatism (2; CAN; KOM; MAB; PHR; PH2); Sore (1; BGB; CRC; MAB; VVG); Swelling (1; BGB); Tendinitis (1; BGB; WAF); Tuberculosis (f; VAG); Ulcer (f; CRC; MAB); Water Retention (f; CAN); Wound (f; CRC; PHR).

I suppose that Commission E is talking about various degenerative arthritic conditions when they approve this for, “Supportive therapy of degenerative disorders of the locomotor system,” but just couldn’t bring themselves around to saying arthrosis, or degenerative joints and/or muscles (KOM).

 

INDICATIONS AND USAGE

Approved by Commission E:

• Dyspeptic complaints

• Loss of appetite

• Rheumatism

Unproven Uses: In folk medicine, Devil's Claw is used as an ointment for skin injuries and disorders. The dried root is used for pain relief; pregnancy discomforts; arthritis; allergies; metabolic disorders; and kidney, bladder, liver and gallbladder disorders. In South Africa it is used for fevers and digestive disorders. Devil's Claw is also used for supportive therapy of degenerative disorders of the CNS system.

Homeopathic Uses: Chronic rheumatism is the primary use for Devil's Claw in homeopamy.

 

PRODUCT AVAILABILITY

Capsules, Dried Powdered Root, Dry Solid Extract, Tea, Tincture

PLANT PARTS USED: ROOTS, Tubers (Secondary Root Tuber)

 

DOSAGES

 

DOSAGES

Anorexia

·        Adult PO infusion: 1.5 g herb tid (Blumenthal, 1998)

Gout

·        Adult PO dried powdered root: 1-2 g tid (Murray, Pizzorno, 1998)

·        Adult PO tincture: 4-5 mL  (1:5 dilution) tid (Murray, Pizzorno, 1998)

·        Adult PO dry solid extract: 400 mg tid (Murray, Pizzorno, 1998)

Osteoarthritis

·        Adult PO dried powdered root: 1-2 g tid (Murray, Pizzorno, 1998)

·        Adult PO tincture: 4-5 mL  (1:5 dilution) tid (Murray, Pizzorno, 1998)

·        Adult PO dry solid extract: 400 mg tid (Murray, Pizzorno, 1998)

Other

·        Adult PO infusion: _4.5 g herb (Blumenthal, 1998) in 300 mL  boiling water, let stand 8 hr, strain and drink

 

DOSAGES

Dosages for oral administration (adults) recommended in older and more contemporary standard herbal reference texts are given below.

Painful Arthrosis and Tendonitis

·        1.5–3 g dried tuber as a decoction, three times daily; 1–3 g drug or equivalent aqueous or hydroalcoholic extracts;(G76)

·        Liquid Extract 1–3mL  (1 : 1, 25% ethanol) three times daily.(G6)

 

Loss Of Appetite Or Dyspepsia

·        Dried Tuber 0.5 g as a decoction, three times daily.(G6)

·        Tincture 1 mL  (1 : 5, 25% ethanol) three times daily.(G6)

Clinical trials of devil's claw root extracts for the treatment of low back pain typically have tested oral doses ranging from 2000– 4500 mg daily, in two or three divided doses (equivalent to less than 30 mg up to 100 mg harpagoside daily, depending on the particular extract), for four to 20 weeks.(13) In a clinical trial in osteoarthritis, participants received capsules containing powdered cryoground devil's claw root 2610 mg daily for four months.(14)

 

DOSAGES

·        1 tsp chopped root/2 cups water, sipped through day (APA); 1.5–4.5(–10) g root (KOM; SHT; SKY);

·        6 g root/day (MAB); 1–2 tsp fresh root (PED); 0.5–1 g dry root (PED);

·        1 g dry root:5 mL  alcohol/5 mL  water (PED); 0.1–0.25 g powdered tuber (PNC);

·        0.1–0.25 g dry tuber as tea 3 x/day (CAN); 0.1–0.25 mL  liquid extract (1:1 in 25% ethanol) 3 x /day (CAN);

·        6–12 mL  liquid extract (1:2)/day (MAB); 15–30 mL  tincture (1:5)/day (MAB);

·        0.5–1 mL  root tincture (1:5 in 25% alcohol) 3 x /day (CAN).

 

DOSAGES

Musculoskeletal Conditions

·        Dried root or equivalent aqueous or hydroalcoholic extracts: 2–6 g daily for painful arthritis; 4.5–9 g daily for lower back pain.

·        Liquid extract (1:2): 6–12 mL /day.

·        Tincture (1:5): 2–4 mL  three times daily.

It is suggested that devil’s claw extracts with at least 50 mg harpagoside in the daily dosage should be recommended for the treatment of pain (Chrubasik 2004a, 2004b).

Digestive Conditions (e.g. dyspepsia)

·        Dosages equivalent to 1.5 g/day dried herb are used (Blumenthal et al 2000). It is suggested that devil’s claw preparations be administered between meals, when gastric activity is reduced.

 

DOSAGES

MODE OF ADMINISTRATION: As comminuted drug for infusions and other preparations for internal use, as an ointment for external use.

HOW SUPPLIED:

         Capsules — 405 mg, 480 mg, 510 mg, 520 mg

         Tablets

PREPARATION: To make an infusion, use 1 teaspoonful (equivalent to 4.5 g) comminuted drug with 300 mL  boiling water. Steep for 8 hours and strain.

DAILY DOSAGE: for loss of appetite, the recommended dosage is 1.5 g of drug; otherwise 4.5 g of drug is used. The infusion can be taken 3 times a day.

HOMEOPATHIC DOSAGE: 5 to 10 drops, 1 tablet or 5 to 10 globules 1 to 3 times a day, or from D3 1 mL  injection solution sc twice weekly (HAB1). The ointment is applied 1 to 3 times a day. For external use, 1 dessertspoon of the tincture should be diluted with 250 mL  and used for washes or poultices.

STORAGE: Store Devil's Claw in a container that protects it from light and moisture.

 

PRECAUTIONS AND ADVERSE REACTIONS

Health risks or side effects following the proper administration of designated therapeutic dosages are not recorded. The drug has a sensitizing effect.

Devil’s claw is a well tolerated treatment. In a recent review of 28 clinical trials it was found that only minor adverse events, mainly mild gastrointestinal symptoms (e.g. diarrhoea), occur in 3% of the patients. The incidence of adverse effects in the treatment groups was never higher than in the placebo groups for all 28 trials (Vlachojannis et al 2008).

Use cautiously in patients with gastric and duodenal ulcers, gallstones or acute diarrhoea, as devil’s claw may cause gastric irritation (Blumenthal et al 2000).

 

CONTRAINDICATIONS, INTERACTIONS, AND SIDE EFFECTS

CLASS 2B, 2D (AHP). Contraindicated in duodenal and gastric ulcers (AHP, 1997). Commission E reports contraindications in GI ulcer (AEH). Contraindicated in people with diabetes. Excessive doses may interfere with blood pressure and cardiac therapy (CAN). LD50 = >13,500 mg/kg orl mouse (CAN).

 

CONTRA-INDICATIONS, WARNINGS

Devil's claw is stated to be contra-indicated in gastric and duodenal ulcers,(G3, G76) and in gallstones should be used only after consultation with a physician.(G3)

Drug Interactions None have been described for devil's claw preparations. However, on the basis of pharmacological evidence of devil's claw's cardioactivity, the possibility of excessive doses interfering with existing treatment for cardiac disorders or with hypo/hypertensive therapy should be considered. Inhibitory effects on certain cytochrome P450 (CYP) drug metabolising enzymes have been documented for a devil's claw root extract (Bioforce) in vitro using a technique involving liquid chromatography-mass spectrometry and automated online extraction.(58) Mean (standard deviation) IC50 values for the devil's claw extract when tested in assays with individual CYP enzymes were 997 (23), 254 (17), 121 (8), 155 (9), 1044 (80) and 335 (14) for the CYPs 1A2, 2C8, 2C9, 2C19, 2D6 and 3A4, respectively.

Pregnancy And Lactation It has been stated that devil's claw has oxytocic properties,(59) although the reference gives no further details and the basis for this statement is not known. In addition, there is no further evidence to substantiate the statement. However, given the lack of data on the effects of devil's claw taken during pregnancy and lactation, its use should be avoided during these periods.

 

CONTRAINDICATIONS

The drug should not be used in the presence of stomach or duodenal ulcers, due to the drug's stimulation of gastric juice secretion.

 

PREGNANCY USE

Devil’s claw is not recommended in pregnancy, as it has exhibited oxytocic activity in animals.

 

CONTRAINDICATIONS

Pregnancy category is 3; Breastfeeding category is 2A. Until more research is available, this herb should not be given to children. Persons with peptic or duodenal ulcer disease, cholecystitis, or hypersensitivity to this herb should avoid the use of devil’s claw.

 

SIDE EFFECTS/ADVERSE REACTIONS

CNS: Headache

CV: Hypotension

EENT: Tinnitus

GI: Nausea, vomiting, anorexia

INTEG: Hypersensitivity reactions

 

INTERACTIONS

Drug

Antacids, H2-blockers, proton pump inhibitors: Devil’s claw may decrease the action of these agents (Jellin et al, 2008).

Antiarrhythmics, antihypertensives: Because two of the chemical components in devil’s claw exert inotropic and chronotropic effects, use this herb cautiously with antiarrhythmics and antihypertensives (theoretical).

Antidiabetics: Devil’s claw may cause an additive effect with antidiabetics (Jellin et al, 2008).

Warfarin: Devil’s claw taken with warfarin may cause risk of bleeding (Jellin et al, 2008).

Lab Test

APTT, PT: Devil’s claw may increase these levels.

 

SIGNIFICANT INTERACTIONS

Devil’s claw has been found to moderately inhibit cytochrome P450 enzymes (CYP2C9, 2C19, 3A4) in vitro (Unger & Frank 2004), however, the clinical relevance of this is yet to be determined. In contrast to NSAIDs, devil’s claw does not affect platelet function (Izzo et al 2005).

Warfarin

Rare case reports suggest that devil’s claw may potentiate the effects of warfarin, but the reports are mostly inconclusive (Argento et al 2000, Heck et al 2000, Izzo et al 2005). Clinical testing would be required to confirm a possible interaction.

Anti-arrythmic Drugs

Theoretical interaction exists when the herb is used in high doses; however, clinical testing is required to determine significance — observe patients taking concurrent antiarrythmics (Fetrow & Avila 1999).

 

EFFECTS

Devil's Claw stimulates gastric juice secretion and is choleretic. Anti-inflammatory, analgesic (and tiius anti-arthritic) effect has been shown in animal experiments.

 

TOXICITY

The acute LD50 of devil’s claw was more than 13.5 g/kg according to one study (Bone & Walker 1997). In a recent review of 28 clinical trials only a few reports on acute toxicity were found, whereas no reports on chronic toxicity had been reported. The review concluded that more studies for longterm treatment are needed (Vlachojannis et al 2008). An earlier review looking at 14 clinical trials had come to the same conclusion (Brien et al 2006).

 

SIDE-EFFECTS, TOXICITY

The mechanism of action of devil's claw remains unclear, in particular, whether it has significant effects on the mediators of acute inflammation. Data from in vitro and clinical studies in this regard do not yet give a clear picture (see Pharmacological Actions, In vitro and animal studies and Clinical studies, Pharmacodynamics). It has been stated that adverse effects associated with the use of NSAIDs are unlikely to occur with devil's claw, even during long-term treatment.(G50, G76) While there are no documented reports of gastrointestinal bleeding or peptic ulcer associated with the use of devil's claw, the latter statement requires confirmation. Use of devil's claw in gastric and duodenal ulcer is contraindicated, although this appears to be because of the drug's bitter properties.(G50)

 

CLINICAL DATA

Randomised, placebo-controlled trials involving patients with rheumatic and arthritic conditions who have received devil's claw extracts or powdered drug at approximately recommended doses for four weeks have reported mild, transient gastrointestinal symptoms (such as diarrhoea, flatulence) in a small proportion (less than 10%) of devil's claw recipients.(43–45) No serious adverse events were reported, although one patient withdrew from one study because of tachycardia.(43)

A small number of reports of randomised trials comparing the effects of devil's claw preparations with those of standard pharmaceutical agents has included data on adverse events. In a randomised, double-blind, pilot trial, 88 participants with acute exacerbations of low back pain received an aqueous extract of devil's claw (Doloteffin; drug to extract ratio 1.5-2.5:1) 2400 mg daily in three divided doses (equivalent to 60 mg harpagoside daily), or rofecoxib (Vioxx) 12.5 mg daily for six weeks.(46) In total, 28 (32%) participants (14 in each group) experienced adverse events, most commonly gastrointestinal complaints (9 in each group).

In a follow-up study, participants in the six-week pilot study were offered continuing treatment with devil's claw aqueous extract two tablets three times daily for up to one year. Participants were not aware of their initial study group (i.e. devil's claw extract or rofecoxib) until towards the end of the oneyear follow-up study.(47) In total, 38 and 35 participants who had previously received devil's claw and rofecoxib, respectively, participated in the follow-up study and, after 24 and 54 weeks, a total of 53 and 43 participants, respectively, remained in the study. Overall, 17 (23%) of the 73 participants in the follow-up study experienced a total of 21 adverse events. Of these, the causality for three events was classified (by a physician not involved in the study) as 'likely' (one allergic skin reaction) or 'possible' (diarrhoea, acid 'hiccup') with respect to devil's claw treatment. Five participants (7%) withdrew from the study because of adverse events. In a randomised, controlled trial comparing devil's claw extract with diacerein in patients with osteoarthritis, numbers of patients ending the study prematurely because of suspected adverse drug reactions were 8 and 14 for devil's claw and diacerein recipients, respectively.(14) In total, 26 diacerein recipients and 16 devil's claw recipients reported one or more adverse events (p = 0.042). The numbers of adverse events attributed to the treatment was significantly lower for devil's claw than for diacerein (10 versus 21; p = 0.017). The most frequently reported adverse event, diarrhoea, occurred in 8.1% and 26.7% of devil's claw and diacerein recipients, respectively.

Several, open, uncontrolled studies,(51–53) which have assessed the effects of devil's claw preparations in patients with arthritic disorders and back pain, have reported data on adverse events. In an open, uncontrolled, multicentre, surveillance study involving patients with arthrosis of the hip or knee, 75 participants received tablets containing an aqueous extract of the secondary tubers of devil's claw (Doloteffin; drug extract ratio = 1.5-2.5 : 1) at a dosage of two 400 mg tablets three times daily (equivalent to 50 mg iridoidglycosides, calculated as harpagoside) for 12 weeks.(51) During the study, four (5%) participants experienced adverse events (dyspeptic complaints, 2; sensation of fullness, 1; panic attack, 1), although none stopped treatment with devil's claw. Causality was assessed as 'possible' for two of these events.

In a similar open, uncontrolled, multicentre study, 130 participants with chronic non-radicular back pain received tablets containing 480 mg devil's claw extract (LI-174; drug extract ratio = 4.4-5 : 1) at a dosage of one tablet twice daily for eight weeks.(52)

Overall, 13 (10%) participants withdrew from the study for various reasons, including no apparent improvement in their condition. No serious adverse events were reported, but three partipants reported minor adverse events (bloating, insomnia and outbreaks of sweating). In a post-marketing surveillance study, 250 patients with non-specific low back pain or osteoarthritic pain of the knee or hip received an aqueous extract of H. procumbens (Doloteffin) at an oral dose equivalent to harpagoside 60 mg daily in three divided doses for eight weeks in addition to any existing treatment and/or additional analgesic medicines as required. Fifty participants experienced adverse events; most commonly gastrointestinal complaints (n = 22); two participants experienced allergic skin reactions.(53) In 27 participants, the adverse event was considered by an independent investigator to be possibly (n = 11), likely (15) or certainly (1) related to ingestion of devil's claw.

In another open, uncontrolled study, one patient withdrew after four days' treatment with devil's claw aqueous extract 1.23 g daily because of several symptoms, including frontal headache, tinnitus, anorexia and loss of taste.(55)

There is an isolated report of conjunctivitis, rhinitis and respiratory symptoms in a 50-year-old woman who had experienced chronic occupational exposure to devil's claw.(56)

 

PRECLINICAL DATA

Acute and subacute toxicity tests in rodents have demonstrated low toxicity of devil's claw extracts. In a study in mice, the acute oral lethal dose (LD) LD0 and LD50 were greater than 13.5 g/kg body weight.(23) In rats, clinical, haematological and gross pathological findings were unremarkable following administration of devil's claw extract 7.5 g/kg by mouth for seven days. Hepatic effects (liver weight, and concentrations of microsomal protein and several liver enzymes) were not observed following oral treatment with devil's claw extract 2 g/kg for seven days.(23) Other studies in mice have reported acute oral acute intravenous LD0 values of greater than 4.64 g/kg and greater than 1 g/kg, respectively.(57) For an extract containing harpagoside 85%, acute oral LD0, acute intravenous LD0 and acute intravenous LD50 values were greater than 4.64 g/kg, 395 mg/kg and 511 mg/kg, respectively.(57)

 

CLIENT CONSIDERATIONS

ASSESS

·        Assess for hypersensitivity reactions. If present, discontinue use of devil’s claw and administer antihistamine or other appropriate therapy.

·        Assess cardiac status in any client with a cardiac condition: blood pressure, character of pulse.

·        Identify what prescription drugs and herbal supplements the client is taking to treat this condition (see Interactions).

·        Assess joint pain and infl ammation in any client with an arthritic condition: pain location, duration, intensity, and alleviating and aggravating factors.

ADMINISTER

·        Instruct the client to store devil’s claw products in a cool, dry place, away from heat and moisture.

TEACH CLIENT/FAMILY

·        Inform the client that pregnancy category is 3 and breastfeeding category is 2A.

·        Caution the client not to use devil’s claw in children until more research is available.

 

PRACTICE POINTS/PATIENT COUNSELLING

·        Devil’s claw reduces pain and inflammation and is a useful treatment in arthritis and back pain, according to controlled studies.

·        The anti-inflammatory action appears to be different to that of NSAIDs and has not been fully elucidated. There is also preliminary evidence of a chondroprotective effect.

·        Preliminary research suggests that it is best to take devil’s claw between meals, on an empty stomach.

·        Devil’s claw appears to be relatively safe but should not be used in pregnancy and should be used with caution in people with ulcers or gallstones or in those taking warfarin.

 

PATIENTS’ FAQs

What will this herb do for me?

Devil’s claw is a useful treatment for arthritis and back pain. It may also increase appetite and improve digestion and dyspepsia.

When will it start to work?

Results from studies suggest that pain-relieving effects will start within 4–12 weeks reaching maximum pain relief after 3–4 months (Chrubasik S et al 2007, Thanner et al 2008).

Are there any safety issues?

Devil’s claw should be used cautiously by people with gallstones, diarrhoea, stomach ulcers and those taking the drug warfarin. It is also not recommended in pregnancy.

 

PREPARATIONS

PROPRIETARY SINGLE-INGREDIENT PREPARATIONS

France: Harpadol; Harpagocid. Germany: Ajuta; Allya; Arthrosetten H; Arthrotabs; Bomarthros; Cefatec; Dolo- Arthrodynat; Dolo-Arthrosetten H; Doloteffin; flexi-loges; Harpagoforte Asmedic; HarpagoMega; Harpagosan; Jucurba; Matai; Pargo; Rheuferm Phyto; Rheuma-Sern; Rivoltan; Sogoon; Teltonal; Teufelskralle. Spain: Fitokey Harpagophytum; Harpagofito Orto.

 

PROPRIETARY MULTI-INGREDIENT PREPARATIONS

Australia: Arthriforte; Arthritic Pain Herbal Formula 1; Bioglan Arthri Plus; Boswellia Compound; Devils Claw Plus; Extralife Arthri-Care; Guaiacum Complex; Herbal Arthritis  Formula; Lifesystem Herbal Formula 1 Arthritic Aid; Prost-1. Czech Republic: Antirevmaticky Caj. France: Arkophytum. Germany: Dr Wiemanns Rheumatonikum. Italy: Bodyguard; Nevril; Pik Gel. Malaysia: Celery Plus. Spain: Dolosul; Natusor Harpagosinol.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

EXTRACTS

German clinical studies confirm arthritic relief; hypocholesterolemic, hypouricemic (PED). Chrubasik et al. (1996) studied the effectiveness in treatment of acute low back pain. While animal studies exhibit analgesic and antiinflammatory activities (due to harpagoside), this study of 118 patients with nonspecific low-back pain (most for more than 15 years),with 400 mg extract 3 ×/day (equivalent of 6000 mg crude root extract = 50 mg harpagoside). Only 9 of the treated patients improved cf 1 in the placebo controls. The insignificant reduction in pain was confined to those whose pain did not radiate to one or both legs. “There was a notable absence of identifiable clinical, hematological, or biochemical side effects” (PHM3:1). None of these authors commented on the presence of 3 COX-2 inhibitors as well, kaempferol, oleanolic acid, and ursolic acid.

 

REFERENCE

 

 

Barnes, J., Anderson, L. A., and Phillipson, J. D. 2007. Herbal Medicines Third Edition. Pharmaceutical Press. Auckland and London.

 

Braun

 

Duke, J. A. with Mary Jo Bogenschutz-Godwin, Judi duCellier, Peggy-Ann K. Duke. 2002. Handbook of Medicinal Herbs 2nd Ed. CRC Press LLC. USA.

 

Gruenwald, J., Brendler, T., Jaenicke, Ch. 2000.  PDR for Herbal Medicines.  Medical Economics Company, Inc. at Montvale, NJ 07645-1742. USA

 

Linda S-Roth. 2010. Mosby’s Handbook Of Herbs & Natural Supplements, Fourth Edition. Mosby Elsevier. USA


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