harpagophytum-procumbens-devils-claw by heku


									          Devil's Claw

Species (Family)                                            Food Use
Harpagophytum procumbens DC . (Pedaliaceae)                 Devil's claw is not used in foods .

                                                            Herbal Use
Harpagophytum, Grapple Plant, Wood Spider
                                                            Devil's claw is stated to possess anti-inflammatory,
                                                                antirheumatic, analgesic, sedative and diuretic
Part(s) Used
                                                            properties . Traditionally, it has been used as a sto-
Secondary root tuber                                        machic and a bitter tonic, and for arthritis, gout,
                                                            myalgia, fibrositis, lumbago, pleurodynia and rheu-
Pharmacopoeial and Other                                    matic disease . (G2,G6,G7,G8,G32,G64) Modern use of
Monographs                                                  devil's claw is focused on its use in the treatment of
                                                            rheumatic and arthritic conditions, and low back
BHC 1992 (G6)                                               pain .
BHP 1996(G9)
BP 2001 (GIS)
Complete German Commission E(G3)                            Dosage
ESCOP 1996 (G52)
Martindale 32nd edition (G43)                               Painful arthrosis and tendonitis
PDR for Herbal Medicines 2nd edition (G36)                  1 .S-3 g dried tuber as a decoction, three times daily ;
Ph Eur 2002 (G28)                                           1-3 g drug or equivalent aqueous or hydroalcoholic
                                                            extracts; 52) liquid extract 1-3 mL (1 : 1, 2S% etha-
Legal Category (Licensed Products)                          nol) three times daily . (G6)
Devil's claw is not included in the GSL . (G37)
                                                            Loss of appetite or dyspepsia
Constituents (132,G6,G62)
                                                            Dried tuber 0.5 g as a decoction, three times
Carbohydrates Fructose, galactose, glucose and              daily . (G6)
myo-inositol (monosaccharides), raffinose, sta-
chyose (46%) and sucrose (oligosaccharides) . ( ' )         Tincture       1 mL (1 :5, 25% ethanol) three times
                                                            daily. (G6)
   lridoids Harpagide, 8-0-(p-coumaroyl)-harpagide,
harpagoside, procumide, 6'-O-(p-coumaroyl)-pro-                  Clinical trials of devil's claw root extracts for the
cumbide, and procumboside (glucosides) .(2) Pharma-         treatment of low back pain have tested doses ranging
 copoeial standard : not less than 1 .2% har a oside,       from 600 to 2400 mg daily, orally, in two or three
  calculated with reference to the dried drug . (GJ5,G25)   divided doses (equivalent to up to 100 mg harpago-
                                                            side (depending on the concentration of the
Phenols Acetoside and isoacetoside (glycosides),            extract)) .(5-7) In a clinical trial in osteoarthritis,
and a bioside.(3)                                           participants received capsules containing powdered
                                                            cryoground devil's claw root 2610 mg daily .( ") Other
Other constituents Amino acids and flavonoids                clinical trials in arthrosic conditions have used daily
(kaempferol, luteolin) .                                      doses of devil's claw of 2 .4 g dried tuber and 2 .46 g
                                                              hydroalcoholic extract . (9) Clinical trials in various
Other plant parts The flower, stem and ripe fruit are         rheumatic conditions have used daily doses of
reporred to be devoid of harpagoside ; the leaf con-          devil's claw of 0 .75-2 g dried tuber and 1 .23 g aqu-
tains traces of irldoids .(4)                                 eous extract in two or three divided doses .(9)


                                                                                               Devil's Claw          175

 pharmacological Acions                                          400 mg/kg, and reached a maximum 3 hours afer
The acive consiuens of devil's claw are widely held           carrageenan injecion . Oher sudies in ras have
o be he iridoid glucosides alhough, of hese, i has           repored significan reducions in oedema using he
nor been definiively esablished wheher harpagoside             same model following prereamen wih inraperio-
                                                                  neal (12,17) and inraduodenal, bu no oral, dried
is he mos imporan pharmacologically acive con-
siuen of he whole exrac . Oher compounds                   aqueous exrac of devil's claw . (12) Oher sudies
presen in he roo may conribue o he pharmaco-               have repored ha dried aqueous exrac of devil's
logical aciviies of devil's claw .(9 ' 10 ' I has also been    claw adminisered orally had no effec on carragee-
                                                                  nan- or Mycobacerium buyricum-induced oedema
suggesed ha harpagogenin, formed by in vivo acid
                                                                  in ra paw . (18,19) In addiion, oral dried aqueous
hydrolysis ) of harpagoside, may have biological
                                                                  exrac of devil's claw had no significan effec in
aciviy .
                                                                  adjuvan-induced arhriis in ras . (18) By conras,
                                                                  in hese sudies, boh indomehacin and aspirin
 In viro and animal sudies                                     displayed significan ani-inflammaory aciv-
 Animal sudies using aqueous exracs of devil's claw           iy (18,19)
 have suggesed ha he exrac may be inacivaed by               Analgesic aciviy has also been documened for
 passage hrough he acid environmen of he so-                devil's claw in animal sudies . Prereamen wih
 mach.        One sudy compared he ani-inflamma-              dried aqueous devil's claw exrac a doses of
 ory aciviies of aqueous devil's claw exrac                  100 mg/kg and above, adminisered inraperione-
 a dminisered by differen roues . Inraperioneal             ally, resuled in peripheral analgesic aciviy demon-
 and inraduodenal adminisraion led o a significan           sraed by a significan reducion in he number of
reducion in he carrageenan-induced ra paw                     wrihings induced by aceic acid in mice . (. 10) How-
 oedema es, bu here was no effec following oral             ever, no effec was observed in he hoplae es,
adminisraion . (12) In anoher sudy, aqueous devil's          indicaing a lack of cenral analgesic aciviy wih
claw exrac prereaed wih hydrochloric acid o                devil's claw exrac . The peripheral analgesic proper-
mimic acid condiions in he somach showed no                   ies of inraperioneal dried aqueous exrac of devil's
aciviy in pharmacological models of pain and                   claw have been confirmed in oher sudies for doses
inflammaion.(10)                                                of 400 mg/kg and above . (17) These sudies also
    Transformaion of he iridoids harpagide, harpa-             repored peripheral analgesic and ani-inflammaory
goside and 8-0-(p-coumaroyl)-harpagide ino he                  properies for he relaed species Harpogophyum
pyridine monoerpene alkaloid aucubinine B, chemi-               zeyheri.(17)
cally or by human inesinal baceria in viro, has                  A clear mechanism of acion for he purpored
been documened. (13,14) However, i is no known if             ani-inflammaory effecs of devil's claw has ye o be
aucubinine B is formed in vivo by inesinal baceria            esablished . In viro, devil's claw (100 mg/mL) had
and, herefore, wheher i conribues o he                    no significan effec on prosaglandin (PG) synhease
pharmacological aciviy of devil's claw . (14)                  aciviy, whereas indomehacin (316 pg/mL) and
    Animal sudies of he ani-inflammaory aciviy             aspirin (437gg/mL) caused 50% inhibiion of his
of devil's claw have repored conflicing resuls .              enzyme.(19) In oher in viro sudies in human whole
Aciviy differs depending on he roue of adminis-              blood samples, devil's claw exracs and fracions of
raion of devil's claw, and he model of inflamma-              exracs were esed for heir effecs on hromboxane
ion, wheher acue or subacue .                                B2 (TXB 2) and leukoriene (LT) biosynhesis . (20)
    Weak ani-inflammaory aciviy has been                     TXB2 is an end-produc of arachidonic acid meabo-
repored in ras following inravenous adminisra-               lism by he cyclooxygenase 1 (COX-1) pahway .
ion of devil's claw exrac .(15) Ani-inflammaory             Inhibiion appeared o be dependen on he harpago-
aciviy of harpagoside has been demonsraed in                 side conen of he exracs or fracions . (20) Harpago-
experimenal models, including he croon oil-                   side (100 pmol/L), bu no harpagide (100 gmol/L),
induced granuloma pouch es, and for harpago-                   inhibied calcium ionophore A23187-simulaed
genin, he aglucone of harpagoside, in he croon                release of TXB2 from human plaeles . (21) However,
oil-induced granuloma pouch es and in formalin-                harpagoside and harpagide had no significan inhibi-
induced arhriis in ras . (16) Dried aqueous exrac of        ory effec on calcium ionophore A23187-simulaed
devil's claw adminisered by inraperioneal injecion           release of PGE 2 and LTC 4 from mouse perioneal
demonsraed significan aciviy in he carrageenan-            macrophages . (21) In viro inhibiion of umour-necro-
induced oedema es in ras, an acue model of                   sis-facor-a (TNF-x) synhesis in lipopolysaccharide-
inflammaion The effec on oedema was dose
."0)                                                             simulaed human monocyes by a hydroalcoholic
dependen for doses of devil's claw exrac 100-

176        Devil's Claw

extract of devil's claw (SteiHap 69) has also been         claw extract, although this needs further investiga-
documented .' 22)                                          tion . (20)
   Crude methanolic extracts of devil's claw have
been shown to be cardioactive in vitro and in vivo         Pharmocodynomics      A study involving healthy
in animals . A protective action against ventricular       volunteers investigated the effects on eicosanoid
arrhythmias induced by aconitine, calcium chloride,        production of orally administered devil's claw (four
epinephrine (adrenaline)/chloroform and reperfusion        500-mg capsules of powder, containing 3% glucoir-
has been reported for devil's claw given intraperito-      idoids, daily for 21 days) .(28) No statistically signifi-
neally or added to the reperfusion medium . (23,24 ) The   cant differences on PGE2, TXB 2 , 6-keto-PGF, O and
crude extract was found to exhibit greater activity        LTB4 were observed following the period of devil's
than pure harpagoside . (24) In isolated rabbit heart,     claw administration, compared with baseline values .
low concentrations of a crude methanolic extract had       By contrast, in a subsequent study involving whole
mild negative chronotropic and positive inotropic          blood samples taken from healthy male volunteers, a
effects, (2 ) whereas high concentrations caused a         biphasic decrease in basal cysteinyl-leukotriene (Cys-
marked negative inotropic effect with reduction in         LT) biosynthesis, compared with baseline values, was
coronary blood flow . 3) In anaesthetised dogs,            observed following oral administration of devil's
harpagoside administered orally by gavage caused a         claw extract (WS1531 containing 9% harpagoside)
decrease in mean aortic pressure and arterial and          600, 1200 and 1800 mg as film-coated tablets . (20)
pulmonary capillary pressure . (25)
    In vitro, harpagoside has been shown to decrease       Therapeutic activity   The efficacy and effectiveness of
the contractile response of smooth muscle to acetyl-       devil's claw has been investigated in more than 10
choline and barium chloride on guinea-pig ileum and        clinical studies involving patients with rheumatic and
                                                                                                        (9,29) These
rabbit jejunum . (26) Harpagide was found to increase      arthritic conditions, and low back pain .
this response at lower concentrations, but antago-         studies have involved different methodological
nised it at higher concentrations . (26) On the basis of   designs, including several uncontrolled studies, and
these studies in isolated smooth muscle, it was            different preparations of devil's claw, including crude
suggested that the constituents of devil's claw may        drug and aqueous extracts . These studies have been
influence mechanisms regulating calcium influx . (26)      summarised elsewhere, (9,29,G56) and several are dis-
    Methanolic extracts have also exhibited hypo-          cussed in detail below.
tensive properties in normotensive rats, causing a            A randomised, double-blind, placebo-controlled
decrease in arterial blood pressure following oral         study involving 118 patients with acute exacerba-
doses of 300 mg/kg and 400 mg/kg body weight . (23)        tions of chronic low back pain investigated the effects
    Devil's claw extracts possess weak antifungal          of devil's claw extract 800 mg three times daily
activity against Penicillium digitatum and Botrytis        (equivalent to 50 mg harpagoside daily) for four
cinerea .(2                                                weeks .(7) There was no statistically significant differ-
                                                           ence between the devil's claw and placebo groups in
                                                           the primary outcome measure - consumption of the
Clinical studies                                           opioid analgesic tramadol over weeks 2-4 of the
Phormocokinetics There is little published informa-        study - among the 109 patients who completed the
tion on the pharmacokinetics of devil's claw extract       study . This was an unusual choice of primary out-
in humans. A pharmacokinetic study involving a             come measure as it gives no direct indication of the
small number of healthy male volunteers (n = 3)            degree of pain experienced by participants . There
measured plasma harpagoside concentrations after           was a trend towards improvement in a modified
oral administration of devil's claw extract (WS1531        version of the Arhus Low Back Pain Index (a mea-
containing 9% harpagoside) 600, 1200 and 1800 mg           sure of pain, disability and physical impairment) for
as film-coated tablets . (20) Maximal plasma concen-       devil's claw recipients compared with placebo reci-
trations of harpagoside were reached after 1 .3-1 .8       pients, although this did not reach statistical signifi-
hours, and were 8 .2 ng/mL and 27 .8 ng/mL for doses       cance . A greater proportion of patients in the devil's
of harpagoside of 108 and 162 mg, respectively             claw group were pain-free at the end of the study,
(corresponding to 1200 and 1800 mg devil's claw            although this was only a secondary outcome mea-
extract, respectively) . Other studies involving small     sure .
numbers of healthy male volunteers indicated that the          On the basis of these findings, a subsequent
half-life ranged between 3 .7 and 6 .4 hours . Other       randomised, double-blind, placebo-controlled trial
results suggested that there may be low oral absorp-       involving 197 patients with exacerbations of low
tion or a considerable first-pass effect with devil's      back pain tested the effects of two doses of devil's

                                                                                         Devil's Claw         177

 claw (WS1531) extract against placebo .(6) Partici-        matoid arthritis or psoriatic arthropathy who
 pants received devil's claw extract 600 mg or              received tablets of devil's claw aqueous extract
 1200 mg daily (equivalent to 50 mg and 100 mg              1.23g daily for six weeks in addition to their con-
 harpagoside daily, respectively), or placebo, for          ventional drug treatment . There were no significant
 four weeks . There was a statistically significant         changes after 6 and 12 weeks in pain, early morning
 difference (p = 0 .027) between devil's claw and pla-      stiffness, and the Ritchie Articular Index (a method of
 cebo with respect to the primary outcome measure -         assessing joint tenderness), compared with baseline
 the number of patients who were pain-free without          values .( " ) By contrast, other open uncontrolled stu-
 tramadol for at least five days during the last week of    dies of devil's claw involving patients with rheumatic
 the study. However, numbers of patients who were           disorders (who received devil's claw powder 1 .5 g
 pain-free were low (3, 6 and 10 for placebo, devil's       daily for 60 days) (32) or arthrosis (who received
 claw 600 mg daily and devil's claw 1200 mg daily,          devil's claw aqueous extract, containing 2 .5% iri-
 respectively) . Furthermore, this is a non-standard        doid glycosides, 3-9 g daily for 6 months) (33)
 outcome measure . Arhus Low Back Pain Index                reported improvements in pain and `complaints' at
 scores improved significantly in all three groups,         the end of the treatment period compared with base-
 compared with baseline values, although there was          line values .
 no statistically significant difference between groups .      Another study involved 45 patients with osteo- or
    In a randomised, double-blind, placebo-controlled       rheumatoid arthritis who received devil's claw root
 study involving patients with non-specific low back        extract 2.46 g daily for two weeks in addition to non-
 pain, 65 participants received devil's claw extract (LI-   steroidal anti-inflammatory drug (NSAID) treat-
 174, Rivoltan), or placebo, 480 mg twice daily             ment, followed by devil's claw extract alone, for
 (equivalent to 24 mg harpagoside daily) for four           four weeks . (31) It was reported that there were no
weeks .(5) There was a significant improvement              statistically significant changes in pain intensity and
 (p < 0.001) in visual analogue scale (VAS) scores          duration of morning stiffness during the period of
for muscle pain in the devil's claw group, but not          treatment with devil's claw extract alone . In sub-
the placebo group, compared with baseline values,           groups of patients with rheumatoid arthritis and
after two and four weeks' treatment . Differences in        those with osteoarthritis, small decreases were
VAS scores between the two groups were statistically        observed in concentrations of C-reactive protein
significant after four weeks' treatment (p < 0 .001) .      and creatinine, respectively. The design of this study
Significant differences between the two groups in           in terms of the treatment regimen (NSAID followed
favour of devil's claw after four weeks' treatment          by devil's claw extract without a washout period),
were also observed with several other parameters,           however, renders the results difficult to interpret .
including muscle stiffness and muscular ischaemic
pain .
    A randomised, double-blind trial has compared           Side-effects, Toxicity
the efficacy of devil's claw extract with that of           Randomised, placebo-controlled trials involving
diacerein in .122 patients with osteoarthritis of the       patients with rheumatic and arthritic conditions
knee and hip '8 Participants received powdered cryo-        who have received devil's claw extracts or powdered
ground devil's claw (Harpadol) 2 .61 g daily, or            drug at approximately recommended doses for four
diacerein 100 mg daily, for four months .                   weeks have reported mild, transient gastrointestinal
    VAS scores for spontaneous pains improved sig-          symptoms (such as diarrhoea, flatulence) in a small
nificantly in both groups, compared with baseline           proportion (less than 10%) of devil's claw recipi-
values, and there were no differences between devil's       ents . f -71 No serious adverse events were reported,
claw and diacerein with respect to VAS scores .             although one patient withdrew from one study
    In a placebo-controlled study involving 89              because of tachycardia. (7 In an open, uncontrolled
patients with rheumatic complaints, devil's claw            study, one patient withdrew after four days' treat-
recipients (who received powdered crude drug 2 g            ment with devil's claw aqueous extract 1 .23g daily
daily for two months) showed significant improve-           because of several symptoms, including frontal head-
ments in sensitivity to pain and in motility (as            ache, tinnitus, anorexia and loss of taste . (31
measured by the finger-to-floor distance), compared            In a randomised, controlled trial comparing
with placebo recipients . (30                               devil's claw extract with diacerein in patients with
    Open, uncontrolled studies involving patients           osteoarthritis, numbers of patients ending the study
with rheumatic and arthritic disorders report con-          prematurely because of suspected adverse drug reac-
flicting results for the effectiveness of devil's claw .    tions were 8 and 14 for devil's claw and diacerein
One study involved 13 patients with arthritis, rheu-        recipients, respectively .(8) In total, 26 diacerein
178         Devil's Claw

   recipients and 16 devil's claw recipients reported one     disorders or with hypo/hypertensive therapy should
   or more adverse events (p = 0 .042) . The numbers of       be considered .
adverse events attributed to the treatment was sig-
   nificantly lower for devil's claw than for diacerein (10   Pregnancy and lactation It has been stated that
versus 21 ; p=0 .017). The most frequently reported           devil's claw has oxytocic properties, (36) although
   adverse event, diarrhoea, occurred in 8 .1% and            the reference gives no further details and the basis
   26.7% of devil's claw and diacerein recipients,            for this statement is not known . In addition, there is
   respectively .                                             no further evidence to substantiate the statement .
       There is an isolated report of conjunctivitis, rhi-    However, given the lack of data on the effects of
nitis and respiratory symptoms in a 50-year-old               devil's claw taken during pregnancy and lactation, its
woman who had experienced chronic occupational                use should be avoided during these periods .
   exposure to devil's claw . (35)
       The mechanism of action of devil's claw remains
                                                              Pharmaceutical Comment
   unclear, in particular, whether it has significant
 effects on the mediators of acute inflammation .             The chemistry of devil's claw has been well docu-
 Data from in vitro and clinical studies in this regard       mented . The iridoid constituents are thought to be
   do not yet give a clear picture (see In vitro and animal   responsible for the reputed anti-inflammatory activ-
 studies and Clinical studies, Pharmacodynamics) . It         ity of devil's claw, although it is not known precisely
   has been stated that adverse effects associated with       which of these are the most important for pharma-
 the use of NSAIDs are unlikely to occur with devil's          cological activity, and the importance of other com-
 claw, even during long-term treatment . (cso,G52)             pounds . There is conflicting evidence from in vitro,
 While there are no documented reports of gastroin-            animal and human studies regarding the anti-inflam-
 testinal bleeding or peptic ulcer associated with the         matory activity of devil's claw and possible mechan-
 use of devil's claw, the latter statement requires            isms of action . Several randomised trials using devil's
 confirmation. Use of devil's claw in gastric and              claw extracts standardised on harpagoside content
 duodenal ulcer is contraindicated, although this              have reported superiority over placebo for some
 appears to be because of the drug's bitter proper-            aspects of low back pain and rheumatic complaints .
 ties . (G50)                                                  However, some studies used non-standard outcome
       Acute and subacute toxicity tests in rodents have       measures and carried out several post-hoc analyses .
 demonstrated low toxicity of devil's claw extracts . In       Further studies have used recognised, predefined
 a study in mice, the acute oral lethal dose (LD) LD o         outcome measures to establish the therapeutic value
 and LD50 were greater than 13 .5 g/kg body                    of standardised devil's claw extracts in patients with
 weight.(19) In rats, clinical, haematological and             arthritic and rheumatic conditions .
  gross pathological findings were unremarkable fol-                On the basis of randomised controlled trials
  lowing administration of devil's claw extract 7 .5 g/kg      involving patients with arthritic and rheumatic dis-
  by mouth for seven days . Hepatic effects (liver             orders, devil's claw extracts appear to have a favour-
  weight, and concentrations of microsomal protein             able short-term adverse effect profile when taken in
   and several liver enzymes) were not observed follow-        recommended doses. Mild, transient gastrointestinal
   ing oral treatment with devil's claw extract 2 g/kg for     effects, such as diarrhoea and flatulence, may occur .
   seven days . (19) Other studies in mice have reported       Chronic toxicity studies and clinical experience with
   acute oral acute intravenous LD o values of greater         prolonged use are lacking, so the effects of long-term
   than 4 .64 g/kg and greater than 1 g/kg, respec-            use are not known . On this basis, and in view of the
   tively .(15) For an extract containing harpagoside          possible cardioactivity of devil's claw, devil's claw
   85%, acute oral LDo, acute intravenous LD o and             should not be used for long periods of time at doses
   acute intravenous LD S 0 values were greater than           higher than recommended. Further studies involving
   4.64 g/kg, 395 mg/kg and 511 mg/kg, respectively . (15)     large numbers of patients are required .
                                                                    Some commercial extracts of devil's claw root
Contra-indications, Warnings                                   may have been prepared not only from the roots of
                                                               H. procumbens, but also from the roots of H . zeyheri,
Devil's claw is stated to be contra-indicated in gastric       which are similar macroscopically. (17) However, the
and duodenal ulcers,(G3 'x52) and in gallstones should          two species differ in the concentration of the consti-
be used only after consultation with a physician . (G3)         tuents harpagoside and 8-O-p-coumaroyl-harpagide .
On the basis of pharmacological evidence of devil's             On this basis it has been stated that the species can be
claw's cardioactiviry, the possibility of excessive             distinguished chemically by determining the ratio
doses interfering with existing treatment for cardiac           harpagoside :8-O-p-coumaroyl-harpagide . The ratio

                                                                                         Devil's Claw           179

is stated to be ear o e for H . zeyheri a d betwee 20      12 Soulima i R et al . The role of stomachal digestio
a d 38 for H. procumbe s which has a low 8-O-p-                o the pharmacological activity of pla t extracts,
cou maroyl-harpagide co te t .        While this ratio         usi g as a example extracts of Harpagophytum
ma y be sufficie t for chemotaxo omic differe tia-             procumbe s . Ca J Physiol Pharmacol 1994 ; 72 :
tio , it may ot be adequate for quality co trol . (37)         1532-1536 .
Other studies have demo strated that the harpago-          13 Baghdikia B et al . Two ew pyridi e mo o-
side co te t of several powdered dry extracts of               terpe e alkaloids by chemical co versio of a
devil's claw from differe t ma ufacturers varies,              commercial extract of Harpagophytum procum-
a d that each $extract has a u ique profile of other           be s . J Nat Prod 1999 ; 62 : 211-213 .
                                                           14 Baghdikia B et a!. Formatio of itroge -co tai -
co stitue ts .
                                                               i g metabolites from the mai iridoids of Harpa-
                                                               gophytum procumbe s a d H. zeyheri by huma
Refere ces
                                                               i testi al bacteria . Pla ta Med 1999 ; 65 : 164-166 .
See also Ge eral Refere ces G2, G3, G5, G6, G9,            15 Erdos A et al . Beitrag zur pharmakologie a d
G15, G25, G31, G32, G36, G43, G49, G50, GS2,                   toxikologie verschiede er extrakte, sowie des
G56, G62 a d G64 .                                             harpagosids aus Harpagophytum procumbe s
                                                               DC . Pla ta Med 1978 ; 34 : 97-108 .
 1    Ziller KH a d Fra z G. A alysis of the water-
                                                           16 Sticher O . Pla t mo o-, di- a d sesquiterpe oids
      soluble fractio from the roots of Harpagophytum
                                                               with pharmacological a d therapeutical activity .
      procumbe s . Pla ta Med 1979; 37: 340-348 .
                                                               I : Wag er H, Wolff P, eds . New Natural Products
 2    Kikuchi T et al. New iridoid glucosides from
                                                               with Pharmacological, Biological or Therapeutical
      Harpagophytum procumbe s DC . Chem Pharm
      Bull 1983 ; 31 : 2296-2301 .                             Activity . Berli : Spri ger Verlag, 1977 : 137-176 .
      Burger JFW et al. Iridoid a d phe olic glycosides    17 Baghdikia B et al. A a alytical study, a ti-
      from Harpagophytum procumbe s . Phytochemis-             i flammatory a d a algesic effects of Harpago-
      try 1987; 26 : 1453-1457.                                phytum procumbe s a d Harpagophytum zeyheri.
 4   Czyga FC, Krueger A . Pharmaceutical biological           Pla ta Med 1997 ; 63 : 171-176 .
      studies of the ge us harpagophytum . Part 3          18 McLeod DW et al . I vestigatio s of Harpagophy-
      Distributio of the iridoid glycoside harpagoside         tum procumbe s (devil's claw) i the treatme t of
      i the differe t orga s of Harpagophytum pro-             experime tal i flammatio a d arthritis i the rat .
      cumbe s a d Harpagophytum zeyheri . Pla ta Med           Br J Pharmacol 1979 ; 66 : P140.
      1977 ;31 :305-307.                                   19 Whitehouse LW et al. Devil's claw (Harpagophy-
 5   Gobel H et a!. Harpagophytum extract LI 174               tum procumbe s) : o evide ce for a ti-i flamma-
      (Devil's claw) for treati g o -specific back pai .       tory activity i the treatme t of arthritic disease .
      Effects o se sory, motor a d vascular muscle             Ca Med Assoc j 1983 ; 129 : 249-251 .
      respo se . Schmerz 2001 ; 15 : 10-18 .               20 Loew D et al. I vestigatio s o the pharmaco-
 6   Chrubasik S et al. Effective ess of Harpagophytum         ki etic properties of Harpagophytum extracts a d
      extract WS 1531 i the treatme t of exacerbatio           their effects o eicosa oid biosy thesis i vitro a d
      of low back pai : a ra domized, placebo-co -             ex vivo. Cli Pharmacol Ther 2001 ; 69 : 356-364 .
      trolled, double-bli d study . Eur J A aesthesiol     21 Be ito PB et al . Effects of some iridoids from pla t
      1999 ; 16: 118-129 .                                     origi o arachido ic acid metabolism i cellular
 7   Chrubasik S et al. Effective ess of Harpagophytum         systems . Pla ta Med 2000; 66 : 324-328 .
      procumbe s i treatme t of acute low back pai .       22 Fiebich BL et a!. I hibitio of TNF-a sy thesis i
      Phytomedici e 1996 ; 3 : 1-10 .                          LPS-stimulated primary huma mo ocytes by
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