Table 9.
Experiments regarding other effects of devil’s claw preparations and compounds.
| Effect | Study | Type | Year | Reference |
|---|---|---|---|---|
| Antioxidant | Rats, Harpagophytum * extract, 100 and 200 mg/kg bw or selegiline i.p. for 1, 7, or 14 days; dose-dependent increase of superoxide dismutase, catalase, and glutathione peroxidase activities and reduction of lipid peroxidase similar to selegiline after 7 days. | In Vivo | 1998 | Bhattacharya and Bhattacharya [352] |
| Luminol-enhanced chemiluminescence in a xanthine/xanthine oxidase cell-free system; Harpagophytum root powder; superoxide and peroxyl were scavenged dose-dependently. | In Vitro | 2002 | Langmead et al. [353] | |
| Trolox equivalent antioxidant capacity (TEAC) assay; Harpagophytum aqueous extract (2.6% harpagoside) and harpagoside; extract rich in water-soluble antioxidants, harpagoside showed poor activity. | In Vitro | 2003 | Betancor-Fernandez et al. [354] | |
| Rat renal mesangial cells; IL-1β-induced NO formation and transcriptional regulation of iNOS; H. procumbens extracts with varying harpagoside content and pure harpagoside; dose-dependent and harpagoside-independent inhibition of iNOS expression. | In Vitro | 2004 | Kaszkin et al. [350] | |
| Harpagophytum aqueous extract; protection from DNA-damaging effects of stannous chloride in proficient and deficient E. coli model; possible chelating, scavenger, or oxidant activity postulated. | In Vitro | 2007 | Almeida et al. [355] | |
| Antioxidant characteristics using in vitro test systems, DPPH radical scavenging, stimulated nitrite generation, neutrophil superoxide anion generation, and neutrophil myeloperoxidase (MPO); Harpagophytum extract (1.2% harpagoside), tincture, harpagoside; dose-dependent effect in all models, minimal scavenging activity of harpagoside. | In Vitro | 2005, 2009 | Grant et al. [349], Grant [356] | |
| Antioxidant activities of total methanol extracts, fractions (phenylethanoids, terpenoids, and sugars), and β-OH-verbascoside, verbascoside, and leucosceptoside from cell suspension culture of H. procumbens; DPPH, superoxide anion generation, and oxygen radical absorbance capacity (ORAC) assays; β-OH-verbascoside most active in DPPH and superoxide anion generation, leucosceptoside in ORAC. | In Vitro | 2010 | Georgiev et al. [357] | |
| Ferric-reducing antioxidant power test; H. procumbens crude methanolic extract, phenylethanoid-containing fraction, and verbascoside; strong ferrous ion-chelating capacity. | In Vitro | 2011 | Georgiev et al. [358] | |
| Brain homogenates, catalase activity and thiol levels, brain cortical slices; lipid peroxidation, antioxidant defenses, cell damage, respectively; H. procumbens infusion, crude extract, and fractions; dose-dependent inhibition of lipid peroxidation, ethyl acetate fraction had the highest antioxidant effects. | In Vitro | 2013 | Schaffer et al. [359,360] | |
| Human neutrophils challenged with phorbol myristate acetate (PMA), opsonized Staphylococcus aureus, and Fusobacterium nucleatum; 5 taxa of Harpagophytum, including one hybrid; high variability in suppression of respiratory burst, hybrid with highest antioxidant capacity but proinflammatory effect, three taxa with anti-inflammatory effect. | In Vitro | 2016 | Muzila et al. [361] | |
| Adult male Wistar rats, fluphenazine-induced orofacial dyskinesia (OD); DPPH assay; ethyl acetate fraction of H. procumbens (10, 30, or 100 mg/kg i.p.); inhibition of vacuous chewing movements, decreased locomotion unchanged, protective against change in catalase activity, not against ROS increase. | In Vivo | 2016 | Schaffer et al. [362] | |
| Porcine neutrophils; respiratory burst; harpagoside; significant inhibition of ROS production. | In Vitro | 2017 | Mosca et al. [363] | |
| Male Sprague–Dawley rats, modified rodent contusion model of spinal cord injury, murine BV-2 microglial cells; H. procumbens hydroethanolic extract (5.3% harpagoside, 300 mg/kg); behavioral and neurochemical parameters, improved, some significantly, in cell line, oxidative stress and inflammatory response were suppressed. | In Vitro and in vivo | 2020 | Ungerer et al. [364] | |
| LPS-induced RAW 264.7 mouse and U937 human macrophages; DPPH and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays; aqueous, ethanolic, and ethyl acetate extracts of H. zeyheri; for all extracts, dose-dependent inhibition of IL-10 expression, ethyl acetate fraction with lowest IC50 in both assays, NO and TNF-α inhibition similar to diclofenac. | In Vitro | 2021 | Ncube et al. [365] | |
| Antidiabetic | Streptozotocin-induced diabetes mellitus in rats; H. procumbens root aqueous extract (50–800 mg/kg i.p.); significant reduction in blood glucose levels in normal and diabetic rats. | In Vitro | 2004 | Mahomed and Ojewole [317], Mahomed [318] |
| Anticholinesterase | Chick, guineapig, and rabbit isolated gastro-intestinal smooth muscle preparations; H. procumbens root aqueous extract (10–1000 µg/mL); dose-dependent contractions of gastro-intestinal tract smooth muscles. | In Vitro | 2005 | Mahomed [318], Mahomed et al. [366] |
| Spectrophotometric method using acetylthiocholine and butyrylcholine chloride as substrates; H. procumbens crude methanolic extract, phenylethanoid-containing fraction, and verbascoside; significant cholinesterase inhibitory activity. | In Vitro | 2011 | Georgiev et al. [358] | |
| Spectrophotometric method, acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibition; H. procumbens ethyl acetate extract and fractions; inhibition by verbascosides > 60% |
In Vitro | 2013 | Bae et al. [351] | |
| Antimicrobial | Harpagophytum extract (not specified) showed mild antifungal effects against Penicillum digitatum and Botrytis cinerea. | In Vitro | 1985 | Guérin and Réveillère [367] |
| Harpagophytum dry extract (2.6% harpagoside) and harpagoside; inhibition of a panel (all) of aerobic bacteria, C. krusei, and two anaerobic bacteria strains, harpagoside without effect. | In Vitro | 2007 | Weckesser et al. [368] | |
| Chloroquine (CQ)-sensitive and CQ-resistant strains of P. falciparum, and cytotoxicity in CHO and HepG2 cells; extracts of H. procumbens aerial parts and seeds, and petrol ether of the root, (+)-8,11,13-totaratriene-12,13-diol and ferruginol, and CQ diphosphate as control; the two diterpenes showed significant inhibition of both strains without being cytotoxic. | In Vitro | 2003 | Clarkson et al. [200] | |
| Female Balb/c mice, infected with Toxocara canis; Harpagophytum ethanolic extract (100 mg/kg); decrease in eosinophil accumulation, IL-5 and IgE significantly decreased. | In Vivo | 2012, 2014 | Oliveira et al. [369,370,371] | |
| Harpagophytum ethanolic extract showed dose-dependent effect on Schistosoma mansoni, mechanism of action proposed; proteins relevant for cellular homeostasis identified as possible targets. | In Vitro | 2014 | Correia [372] | |
| Bacterial triggers of rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, and rheumatic fever; powdered Harpagophytum extracts, various solvents; inhibition of Proteus mirabilis, Klebsiella pneumoniae, Acinetobacter baylyi, Pseudomonas aeruginosa, and Streptococcus pyogenes throughout, methanolic extract more potent, no toxicity in Artemia nauplii bioassay. (Note: throughout the publication, the substance of investigation is mislabeled as devil’s claw fruit, while it was, in fact, the root being investigated (pers. comm. Ian Cock, 2021)) | In Vitro | 2017 | Cock and Bromley [373] | |
| Antimutagenic | Cultured human lymphocytes; mutagenic activity of 1-nitropyrene (1-Npy) in cytokinesis-block micronucleus assay; Harpagophytum aqueous-ethanolic extract, harpagoside; genotoxicity significantly reduced for both, only harpagoside significantly reduced the mutagenicity of 1-Npy. | In Vitro | 2014, 2015 | Luigi [374], Luigi et al. [375] |
| Anti-osteoporotic | Male ICR mice, female C57BL/6J mice; receptor activator of nuclear factor κ-Β ligand (RANKL)-induced osteoclastogenesis; harpagoside; inhibition of RANKL, osteoclast formation, and LPS-induced bone loss, but not ovariectomy-mediated bone erosion. | In Vitro | 2015 | Kim et al. [376] |
| Mouse calvaria MC3T3-E1cells; bone formation and resorption, bone-loss in ovariectomized (OVX) mouse model; harpagide; stimulated differentiation and maturation of osteoblast cells and suppressed RANKL-induced osteoclastogenesis, improved bone recovery in OVX model, inhibited markers of bone loss in the serum. | In Vitro and in vivo | 2016 | Chung et al. [377] | |
| Mouse calvaria MC3T3-E1cells; bone formation and resorption, bone-loss in ovariectomized (OVX) mouse model; harpagoside; stimulated differentiation and maturation of osteoblast cells and suppressed RANKL-induced osteoclastogenesis, improved bone recovery in OVX model, inhibited markers of bone loss in the serum. | In Vitro and in vivo | 2017 | Chung et al. [378] | |
| Cardiovascular | Frog and guineapig hearts, cats; cardiac muscle contraction and blood pressure, dose-dependent positive and negative inotropic effects, no effect on blood pressure. | In Vitro and in vivo | 1965 | Vollmann [379] |
| Normotensive rats, rabbit heart; methanolic extract of Harpagophytum, harpagoside, harpagide; decrease in blood pressure and heart rate observed, less with harpagoside; extract mild inotropic at lower and negative inotropic at higher doses, harpagoside more negative chronotropic and positive inotropic, harpagide only slightly negative chronotropic but considerably negative inotropic. | In Vitro and in vivo | 1984 | Circosta et al. [380] | |
| Rat heart; methanolic extract of Harpagophytum (8.5% harpagoside and 10.5% total iridoids) and harpagoside; significant, dose-dependent, protective action toward hyperkinetic ventricular arrhythmias. | In Vitro | 1985 | De Pasquale et al. [381] | |
| Langendorff preparations of rat heart; ischemic perfusion induced hyperkinetic ventricular arrhythmia; H. procumbens, harpagoside; significant, dose-dependent protective action for both. | In Vitro | 1985 | De Pasquale et al. [382] | |
| Guineapig ileum and rabbit jejunum; Harpagophytum extract, harpagoside, harpagide; spasmolytic effect, strongest for harpagoside. | In Vitro | 1985 | Occhiuto et al. [383] | |
| Dogs; harpagoside, harpagide (3.4 mg/kg); decrease of mean aortic pressure with harpagoside. | In Vivo | 1990 | Occhiuto and de Pasquale [384] | |
| Multiple mammalian animal models; H. procumbens root aqueous extract (10–400 mg/kg i.v., 10–1000 µg/mL); dose-dependent, significant hypotensive, cardio-depressant, and vasorelaxant effects. | In Vitro and in vivo | 2004 | Mahomed and Ojewole [385], Mahomed [318] | |
| Neuroprotective | Pentylenetetrazole (PTZ)-, picrotoxin (PCT)-, and bicuculline (BCL)-induced seizures in mice; H. procumbens aqueous extract (100–800 mg/kg i.p.); PZT-induced seizures significantly reduced, PCT and BCL to a lesser extent, CNS depressed. | In Vivo | 2006 | Mahomed and Ojewole [386] |
| Rat hypothalamic (Hypo-E22) cells and rat cortex challenged with amyloid β-peptide; H. procumbens aqueous extract; increased brain-derived neurotrophic factor gene expression and decreased TNF-α gene expression in Hypo-E22 cells, alleviated decreased monoaminergic signaling in cortex presynaptic endings. | In Vitro and ex vivo | 2017 | Ferrante et al. [387] | |
| Male Wistar rats; chronic cerebral hypoperfusion model; harpagoside (15 mg/kg, 60 days); symptoms of vascular dementia spatial and fear memory impairments restored, phosphatase and tensin homolog (PTEN) significantly suppressed. | In Vivo | 2018 | Chen et al. [388] | |
| Female Wistar albino rats, arsenic induced neurotoxicity; Harpagophytum powder (200 and 400 mg/kg, p.o.); behavioral and biochemical parameters improved significantly. | In Vivo | 2020 | Peruru et al. [389] | |
| Immunomodulatory/thymomimetic | Maturation of mice thymocytes in the presence of a glycocorticosteroid, cytotoxicity by microscopy and flow cytometry; ethanolic extract of Harpagophytum, Filipendula ulmaria, and Echinacea purpurea, various dilutions; 17% increase in the number of surviving cells. | In Vitro | 2002 | Prosinska et al. [390] |
| Anorexigenic | Male C57BL/6 mice, calcium mobilization and growth hormone secretagogue receptor (GHS-R1a) internalization; Harpagophytum root powder; significantly increased cellular calcium influx but no induction of GHS-R1a receptor internalization, significant anorexigenic effect. | In Vivo | 2014 | Torres-Fuentes et al. [391] |
| Male Wistar rats; obestatin secretion; Harpagophytum hydroalcoholic extract (150, 300, and 600 mg/kg); significantly increased serum levels of obestatin and reduced body weight at 300 and 600 mg/kg. | In Vivo | 2016 | Saleh et al. [392] | |
| Metal accumulation | Rats, supplemented with lead acetate; Harpagophytum infusion (30 mg/kg); significant reduction of lead deposits | In Vitro | 1975 | Int. Bio Research [393] |
* Species not specified; however, all specific attribution must be cautioned against due to the frequent admixture.