Dermal and Transcutaneous Delivery of the Major Glycoside Constituents of Harpagophytum procumbens (Devil’s Claw) in vitro

Abstract

The potential of the administration of Harpagophytum procumbens extract via the topical route has not been studied previously. In the current work, the dermal and transcutaneous delivery of the major pharmacologically active constituents present in H. procumbens tuber extract were determined across porcine ear skin from four vehicles: de-ionised water, 30 % ethanol in water (v/v), PEG 400, 50 : 50 PEG 400 in 30 % EtOH (v/v). Permeation profiles were obtained under infinite conditions and tape stripping was performed at 24 h. The permeation of the compounds varied according to their physicochemical properties as well as the nature of the vehicle. The highest permeation was found from the ethanol/water saturated solutions and the lowest MW harpagide was obtained at significantly higher concentrations in the receptor phase compared to the rest of the compounds, with the permeability coefficient being inversely dependent on dielectric constant of the vehicle. Depth profiling revealed higher penetration of all compounds from ethanol/water; in addition, significantly higher amounts of the pro-inflammatory harpagide were present in the strips and the remaining epidermis compared to other compounds. This suggests that ethanol is not a suitable vehicle as it leads to more harpagide penetration, potentially counteracting the anti-inflammatory activity of the other compounds. The development of new systems for local cutaneous inflammation (e. g., psoriasis, eczema) and subcutaneous inflammation (e. g., arthritis) is supported.

Key words

Devils Claw - Harpagophytum procumbens - Pedaliaceae - skin - inflammation - transcutaneous delivery - topical delivery

References

• 1 Ernst E, Chrubasik S. Phyto-anti-inflammatories: A systematic review of randomised, placebo-controlled, double-blind trials.  Rheum Dis Clin North Am. 2000;  26 13-27
• 2 Baghdikian H B, Lanhers M C, Fleurentin J, Ollivier E, Maillard C, Balansard G. et al . An analytical study, anti-inflammatory and analgesic effects of Harpagophytum procumbens and Harpagophytum zeyheri.  Planta Med. 2000;  63 171-6.
• 3 Council of Europe (COE) - European Directorate for the Quality of Medicines. European Pharmacopoeia, Volumes I and II, 5th edition. Strasbourg; European Directorate for the Quality of Medicines 2004
• 4 Chrubasik S, Conradt C, Roufogalis B D. Effectiveness of Harpagophytum extracts and clinical efficacy.  Phytother Res. 2004;  18 187-9
• 5 Chantre P, Cappelaere D, Leblan D, Guedon J, Vandermander J, Fournie B. Efficacy and tolerance of Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis.  Phytomedicine. 2000;  7 177-83
• 6 Chrubasik S, Zimper C, Schuett U, Ziegler R. Effectiveness of Harpagophytum procumbens in treatment of acute low back pain.  Phytomedicine. 1996;  3 1-10
• 7 Kundu J K, Mossanda K S, Na H K, Surh Y J. Inhibitory effects of the extracts of Sutherlandia frutescens (L.) R. Br. and Harpagophytum procumbens DC. on phorbol ester-induced COX-2 expression in mouse skin: AP-1 and CREB as potential upstream targets.  Cancer Lett. 2005;  218 21-31
• 8 Boje K, Lechtenberg M, Nahrstedt A. New and known iridoid- and phenylethanoid glycosides from Harpagophytum procumbens and their in vitro inhibition of human leukocyte elastase.  Planta Med. 2003;  69 820-5
• 9 Stewart K M, Cole D. The commercial harvest of devil′s claw (Harpagophytum spp.) in southern Africa: The devil′s in the details.  J Ethnopharmacol. 2005;  100 225-36
• 10 Joubert E, Manly M, Gray B R, Schulz H. Rapid measurement and evaluation of the effect of drying conditions on harpagoside content in Harpagophytum procumbens (Devil’s Claw) root.  J Agric Food Chem. 2005;  53 3493-502
• 11 Fiebich B L, Heinrich M, Hiller K O, Kammerer N. Inhibition of TNF-α synthesis in LPS-stimulated primary human monocytes by Harpagophytum extract SteiHap 69.  Phytomedicine. 2001;  8 28-30
• 12 Lanhers M C, Fleurentin J, Mortier F, Vinche A, Younos C. Antiinflammatory and analgesic effects of an aqueous extract of Harpagophytum procumbens. .  Planta Med. 1992;  58 117-23
• 13 Loew D, Mollerfeld J, Schrodter A, Puttkammer S, Kaszkin M. Investigations on the pharmacokinetic properties of Harpagophytum extracts and their effects on eicosanoid biosynthesis in vitro and in vivo.  Clin Pharmacol Ther. 2001;  69 356-64
• 14 McGregor G, Fiebich B, Wartenberg A, Brien S, Lewith G, Wegener T. Devil’s Claw (Harpagophytum procumbens): An anti-inflammatory herb with therapeutic potential.  Phytochem Rev. 2005;  4 47-53
• 15 Benito P B, Lanza A MD, Sens A MS, Galindez J D, Matellano L F, Gomez A S. et al . Effects of some iridoids from plant origin on arachidonic acid metabolism in cellular systems.  Planta Med. 2000;  66 324-8
• 16 Moussard C, Alber D, Toubin M M, Thevenon N, Henry J C. A drug used in traditional medicine, Harpagophytum procumbens: No evidence for NSAID-like effect on whole blood eicosanoid production in human.  Prostaglandins Leukot Essent Fatty Acids. 1992;  46 283-6
• 17 Tippler B, Syrovets T, Plaza N, Loew D, Simmet T. Harpagophytum procumbens DC used in traditional medicine inhibits eicosanoid biosynthesis in human whole blood.  Int J Tissue React. 1997;  19 101-2
• 18 Jang M H, Lim S, Han S M, Park H J, Shin I, Kim J W. et al . Harpagophytum procumbens suppresses lipopolysaccharide-stimulated expressions of cyclooxygenase-2 and inducible nitric oxide synthase in fibroblast cell line L929.  J Pharmacol Sci. 2003;  93 367-71
• 19 Kaszkin M, Beck K F, Koch E, Erdelmeier C, Kusch S, Pfeilschifter J. et al . Downregulation of iNOS expression in rat mesangial cells by special extracts of Harpagophytum procumbens derives from harpagoside-dependent and independent effects.  Phytomedicine. 2004;  11 585-95
• 20 Abdelouahab N, Heard C M. Effect of Harpagophytum procumbens and its major iridoid glycosides on epidermal COX-2 in vitro. J Nat Prod, in press
• 21 Blumenthal M, Busse W R, Goldberg A. The Complete Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston; Integrative Medicine Communications 2004: 120-1
• 22 Jacobi U, Kaiser M, Toll R, Mangelsdorf S, Audring H, Otberg N. et al . Porcine ear skin: an in vitro model for human skin.  Skin Res Technol. 2007;  13 19-24
• 23 Heard C M, Monk B V, Modley A J. Binding of primaquine to epidermal membranes and keratin.  Int J Pharm. 2003;  257 237-44
• 24 Bos J D, Meinardi M M. The 500 Dalton rule for the skin penetration of chemical compounds and drugs.  Exp Dermatol. 2000;  9 65-6
• 25 Arnold K, Hermann A, Pratsch L, Gawrisch K. The dielectric properties of aqueous solutions of poly(ethylene glycol) and their influence on membrane structure.  Biochem Biophys Acta. 1985;  815 515-8
• 26 Moser K, Kriwet K, Naik A, Kalia Y N, Guy Y N. Passive skin penetration enhancement and its quantification in vitro.  Eur J Pharm Biopharm. 2001;  52 103-12
• 27 Heard C M, Kung D, Thomas C P. Skin penetration enhancement of mefenamic acid by ethanol and 1,8-cineole can be explained by the pull effect.  Int J Pharm. 2006;  321 167-70