Table 4.
In Vitro experiments regarding analgesic/antinociceptive and anti-inflammatory effects of devil’s claw preparations and compounds.
| Study | Year | Reference |
|---|---|---|
| Guineapig isolated ileum; harpagoside (40 µg/mL) and harpagogenine (2.5 µg/mL) non-selectively inhibited contractions; harpagide (40 µg/mL) increased the cholinergic response without inhibitory effects. | 1981 | Fontaine et al. [282] |
| Calcium ionophore-stimulated mouse peritoneal macrophages; harpagoside and harpagide inhibited leukotriene C4 (LTC4) and prostaglandin E2 (PGE2) release (not significant) and harpagoside inhibited thromboxane B2 (TXB2) release, similar to ibuprofen. | 2000 | Benito et al. [283] |
| Lipopolysaccharide-stimulated primary human monocytes; Harpagophytum * extract, harpagoside, and harpagide extract prevented synthesis of tumor necrosis factor alpha (TNF-α), isolated substances showed no effect. | 2001 | Fiebich et al. [284] |
| Ionophore A23187 stimulated Cys-LT levels in anticoagulated whole blood; Harpagophytum extract, harpagoside, and extract fractions; inhibitory effect stronger with extract than harpagoside, no effect with fractions without harpagoside, suggesting relation between serum harpagoside and inhibition of leukotriene biosynthesis. | 2001 | Loew et al. [285] |
| Modified Hens-Egg-Test at the Chorion-Allantoin-Membrane (HET-CAM) and lipoxygenase assay; ethanolic extracts of Harpagophytum (60%, 30%, 0%); 30% most potent in HET-CAM, 60% most potent in inhibiting lipoxygenase pathway. | 2002 | Wahrendorf et al. [286] |
| Human neutrophile elastase (HNE); Harpagophytum extract, fractions, and isolates; weak dose-dependent inhibition was observed, with H. procumbens extract twice as strong as H. zeyheri; 6′-O-acetyl-acteoside (not in H. procumbens) the strongest isolate, followed by isoacteoside and pagoside (dominant in H. zeyheri). | 2002, 2003 | Boje [199]; Boje et al. [201] |
| Lipopolysaccharide (LPS)-induced inflammation in mouse fibroblast cell line L929; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription-polymerase chain reaction, PGE2 immunoassay, and nitric oxide (NO) detection; aqueous H. procumbens extract; suppression of PGE2 synthesis and NO production. | 2003 | Jang et al. [287] |
| Human chondrocytes stimulated with interleukin (IL)-1β; Harpagophytum dry extract (210, 480 mg); immunofluorescence and Western blot analyses showed dose-dependent suppression of matrix metalloproteinases production via inhibition of cytokine expression. | 2004 | Schulze-Tanzil et al. [288] |
| Bovine and human chondrocytes, stimulated with LPS and IL-1β, respectively; Harpagophytum extracts (100, 33, 1 µg/mL); significant suppression of PGE2 expression and NO synthase in human chondrocytes (bovine experiment was flawed). | 2006 | Chrubasik [289], Chrubasik et al. [290], Hadzhiyski et al. [291] |
| Human whole-blood assay, human polymorph nuclear leucocytes (PMNL) assay; COX-2, 5-lipogenase (LOX) inhibition, respectively; comparison of Harpagophytum aqueous-ethanolic and CO2 extracts (2%, 20%, and 30% harpagoside, respectively); variable but weak PGE2 inhibition for all, superiority of CO2 extracts in 5-LOX inhibition. | 2006 | Günther et al. [292] |
| Human HepG2 hepatocarcinoma and RAW 264.7 macrophage cell lines; harpagoside (0.1–200 µM); LPS-induced mRNA, COX-2 expression, and inducible nitric oxide (iNOS) inhibited, and NF-κB activation suppressed. | 2006 | Huang et al. [293] |
| LPS-stimulated THP-1 cells; incubated with 50 µg/mL H. procumbens dry extract (DER 1.5–3); microarray (gene chip) assay; noted inhibition of several inflammatory targets. | 2009 | Balthazar et al. [294] |
| COX-2 (ovine) enzyme, stimulated by arachidonic acid and TMPD; H. procumbens extract, harpagoside, and harpagide; direct inhibition (68%) of COX-2, harpagoside, and harpagide contributed 1.5% and 13%, respectively. | 2011 | Ebrahim and Uebel [295] |
| Isolated murine macrophages; H. procumbens crude methanolic extract, harpagoside, phenylethanoid-containing fraction, verbascoside; strong inhibitory action related to NO and TNF-α and IL-6 production, and COX-1 and COX-2 expression, comparable to harpagoside. | 2011 | Gyurkovska et al. [296] |
| LPS-stimulated human monocytes and mouse RAW264.7 macrophages; molecular targets; H. procumbens ethanolic extract (2.9% harpagoside); dose-dependent inhibition of TNF-α, IL-6, IL-1β, PGE2, and COX-2, inhibition of activator protein (AP)-1 pathway without affecting NF-κB and mitogen-activated protein (MAP) kinase pathways. | 2012 | Fiebich et al. [297] |
| Pre-transdermal and post-transdermal COX-2 inhibition and permeation studies; H. procumbens extract, harpagoside, harpagide; hydroxypropyl cellulose gels (carrier) with permeation enhancers tested on synthetic membranes, with and without enhancers on human skin, Azone® enhancer chosen, direct COX-2 inhibition maintained (pre-permeation 80%, post-permeation 77% COX-2) | 2013 | Ebrahim [298] |
| LPS-stimulated monocytic THP-1 cells; enzyme-linked immunosorbent assays, WST-1 assay; Harpagophytum extract; dose-dependent suppression of TNF-α, IL-6, IL-8, independent from external metabolic activation. | 2014 | Hostanka et al. [299] |
| Primary human osteoarthritis chondrocytes; harpagoside (600 µM); significant reduction in IL-1β-induced expression of IL-6, no effect on nuclear levels of NF-κB. | 2015 | Haseeb et al. [300,301] |
| Differentiated 3T3-L1 adipocytes; harpagoside; activation of peroxisome proliferator-activated receptor (PPAR)-γ, significant inhibition of TNF-α-induced mRNA synthesis and production of atherogenic adipokines including IL-6, plasminogen activator inhibitor-1, and monocyte chemoattractant protein-1. | 2015 | Kim et al. [302] |
| IFN-γ/LPS-stimulated THP-1 cells; harpagoside and harpagide; decreased TNF-α-secretion in PMA-differentiated THP-1 cells, positive effect on TNF-α and intercellular adhesion molecule-1 mRNA-expression in undifferentiated cells. | 2016 | Schopohl et al. [303] |
| Human synovial membranes from subjects with and without osteoarthritis; H. procumbens extract, multiple solvents; cannabinoid type 2 (CB2) receptor enhanced, phosphatidylinositol-specific phospholipase C β2 downregulated with water and DMSO, fatty acid amide hydrolase (FAAH) activity inhibited with all. | 2020 | Mariano et al. [304] |
* Species not specified; however, all specific attribution must be cautioned against due to the frequent admixture.