Table 5.
In Vivo experiments regarding analgesic/antinociceptive and anti-inflammatory effects of devil’s claw preparations and compounds.
| Study | Year | Reference |
|---|---|---|
| Formaldehyde-induced arthritis in rats; Harpagophytum * infusion p.o. and subcutaneous; significant reduction of swelling, subcutaneous application better tolerated. | 1958 | Zorn [116] |
| Albumin-induced paw edema, granuloma-pouch-test, formaldehyde-induced arthritis in rats, rabbit ear-withdrawal test; whole extract and harpagoside, intravenous (i.v.) and i.p.; some (significant) effects shown similar to those of phenylbutazone. | 1970 | Eichler and Koch [305] |
| Rats; blood panel; Harpagophytum aqueous extract 3:1, 30 mg/kg; triglycerides, uric acid, urea, and cholesterol significantly reduced. | 1974 | Int. Bio Research [306] |
| Dextran-induced paw edema; rats; Harpagophytum, aqueous extract 3:1; edema significantly reduced. | 1974 | Int. Bio Research [307] |
| Eight Harpagophytum dry extracts, p.o. and i.v., tested for analgesic and antiphlogistic effects in five animal models; some analgesic and antiphlogistic effects with methanolic, butanolic, and fluid extracts; pure harpagoside superior, semi-chronic models showed better results. | 1978 | Erdös et al. [308] |
| Carrageenan-induced rat paw edema (30) and adjuvant-induced arthritis in rats (40); Harpagophytum 100–1000 mg/kg, single dose and 21 days; no significant effect in the edema model, some effect in the arthritis model at the higher dose. | 1979 | McLeod et al. [309] |
| Carrageenan-induced rat paw edema; aqueous ethanolic crude extract of Harpagophytum and various fractions; only crude extract effective, concludes that harpagoside is likely not the (only) active. | 1986 | Duband [274] |
| Carrageenan-induced rat paw edema; methanolic extract of Harpagophytum; dose-dependent edema inhibition. | 1990 | Mánez et al. [310] |
| Carrageenan-induced rat paw edema; aqueous extract of Harpagophytum (1.8% harpagoside) and harpagoside i.p.; significant reduction of edema with extract, not with harpagoside. | 1992 | Lanhers et al. [311] |
| Adriamycin-induced rat paw edema; Harpagophytum, 37, 370, and 3700 mg/kg; dose-dependent edema inhibition up to 48% after one hour; compared to control (Adriamycin only) effect transient after 5 days. | 1992 | Jadot and Lecomte [312] |
| Carrageenan-induced mouse paw edema and TPA-induced mouse ear edema; harpagoside (p.o. and topically); no notable protective effects. | 1994 | Del Carmen Recio et al. [313] |
| Carrageenan-induced rat paw edema; aqueous extracts of Harpagophytum (400 and 800 mg/kg, 2.72% harpagoside) i.p. pre-treatment, p.o., and intraduodenally; significant inhibition i.p. and intraduodenally, no effect orally. | 1994 | Soulimani et al. [314] |
| Carrageenan-induced mouse paw edema; Harpagophytum and Uncaria tomentosa extracts; no effect on inflammatory response individually, but significant effect combined. | 2002 | Abe et al. [315] |
| Freund’s adjuvant-induced arthritis in rats; acute (25, 50, or 100 mg/kg) or chronic (100 mg/kg) treatments with H. procumbens solution; increased ‘latency of paws’ withdrawal and reduction in paw edema, compared to control. | 2004 | Andersen et al. [316] |
| Fresh egg albumin-induced pedal edema in rats, hot-plate and acetic acid tests in mice; H. procumbens root aqueous extract (50–800 mg/kg i.p.); significant effect against nociceptive pain stimuli and significant, dose-dependent reduction of edema. | 2004 | Mahomed and Ojewole [317], Mahomed [318] |
| Carrageenan-induced back-paw edema, Freund’s adjuvant-induced arthritis, cotton pellet-induced granuloma, and writhing tests in rats and mice; Harpagophytum aqueous extract (800 mg/kg bw), acetyl salicylic acid and indomethacin as controls; significant effects in all models similar to indomethacin and acetyl salicylic acid. | 2005 | Ahmed et al. [319] |
| TPA-induced COX-2 expression in mouse skin; Harpagophytum methanolic extract (200, 400 µg) topically prior to TPA application; significant inhibition of COX-2 expression, COX-1 unchanged, no effect on NF-κB. | 2005 | Kundu et al. [320] |
| Carrageenan-induced back-paw edema in rats; H. procumbens extract (100, 200, 400, or 800 mg/kg) p.o. and i.p.; reduced intensity of inflammatory response when given i.p. | 2006 | Catelan et al. [321] |
| Adult female white New Zealand rabbits, anterior cruciate ligament transected, and medial meniscus removed; Harpagophytum extract (150 mg/day), standard food pellets as control; outcome suggests suppression of metalloproteinase-2 production. | 2006 | Chrubasik et al. [322], Chrubasik [289] |
| Male ICR mice; formalin test; Harpagophytum extract (1.9% harpagoside, 30–300 mg/kg); significant dose-dependent attenuation of licking/biting and spinal nitrites/nitrates. | 2008 | Uchida et al. [323] |
| Rabbits after unilateral meniscectomy and transection of the anterior cruciate ligament; thickness, surface area, and volume of the tibial condylar cartilage per MRI; H. procumbens extract (14% harpagoside); difference in thickness and volume between healthy and operated leg slightly but not significantly smaller with Harpagophytum. | 2011, 2014 | Wachsmuth et al. [324], Wrubel [325] |
| BALB/c mice infected with Salmonella enteritidis; leukocytes, neutrophils, and mononuclear cell counts, TNF-α, IL-4, 10, 12, histopathological analysis of the liver and small intestine; H. procumbens extract (150 µg/day); downregulation of cell counts, TNF-α, IL-10 m 12, IL-4 increased, histopathology of liver unchanged, hypertrophy in the small intestine, reduced with Harpagophytum. | 2014 | Bisinotto [326] |
| Male SD rats; plantar incision and spared nerve injury; mechanical withdrawal threshold (MWT) test and ultrasonic vocalization (USVs); H. procumbens ethanolic extract (300 mg/kg, p.o.); MWT significantly increased, USVs reduced. | 2014 | Lim et al. [327] |
| Rats; carrageenan-induced mechanical allodynia and thermal hyperalgesia, involvement of the hemeoxygenase (HO)-1/carbon monoxide (CO) pathway; H. procumbens extract (300 and 800 mg/kg i.p.); pretreatment with HO inhibiter reduced anti-hyperalgesic effect, pretreatment with hemin- or CO-releasing molecule induced antiallodynic response. | 2015 | Parenti et al. [328] |
| Rats; formalin-induced damage to cartilage tissue; combination of glucosamine hydrochloride, chondroitin sulfate, methylsulfonylmethane, Harpagophytum extract (3% harpagoside), and bromelain extract (500 mg/kg); malondialdehyde, NO, 8-hydroxyguanine, IL-1β, and TNF-α significantly lowered, glutathione significantly increased. | 2015 | Ucuncu et al. [329] |
| Rats, chronic constriction injury (CCI) of left sciatic nerve model; Harpagophytum extract + morphine, each at sub-analgesic dose; significant antiallodynic and anti-hyperalgesic effect suggesting synergistic effect. | 2016 | Parenti et al. [330] |
| Immunological angiogenesis induced by bronchoalveolar lavage (BAL) cells grafted into BALB/c mice skin; ethanolic extract of Harpagophytum, Filipendula ulmaria, and Echinacea purpurea; significant reduction of newly formed blood vessels 1.2 and 0.6 mg daily. | 2016 | Radomska-Lesniewska et al. [331] |
* Species not specified; however, all specific attribution must be cautioned against due to the frequent admixture.