Anti-Inflammatory and Antiallergic Activity in vivo of Lipophilic Isatis tinctoria Extracts and Tryptanthrin

Abstract

The effects of a supercritical CO₂ (SFE) extract, a dichloromethane (DCM) extract from Isatis tinctoria leaf and the alkaloidal constituent tryptanthrin were studied in acute and subchronic experimental models of inflammation. The SFE and DCM extracts showed anti-inflammatory activity in the carrageenan-induced acute mouse paw oedema (ED₅₀ values of 78 mg/kg and 165 mg/kg p. o., respectively) and in the acute tetradecanoylphorbol acetate (TPA)-induced mouse ear oedema in oral (62 % and 32 % oedema reduction at 100 and 125 mg/kg, respectively) and topical application (37 % and 33 % reduction of oedema at 0.5 mg/ear). In contrast, tryptanthrin showed no significant anti-inflammatory effect. The DCM extract inhibited oedema formation and neutrophil infiltration in subchronic inflammation in mice induced by repeated application of TPA. The extract showed activity after oral and topical administration by reducing the various parameters of the inflammatory response. The DCM extract (1 mg/ear) inhibited the delayed-type hypersensitivity (DTH) reaction induced by application of dinitrofluorobenzene (DNFB) after topical application. The response during the induction phase (24 h) was decreased by 48 %, and the inflammatory phase (48 to 96 h) was reduced by 53 to 56 %. The extract had no effect in this model when administered orally. The DCM extract (200 mg/kg p. o.) inhibited the acetic acid-induced writhing by 49 %.

Anti-inflammatory agents - antiallergic - Isatis tinctoria - Brassicaceae - tryptanthrin - inflammation - delayed-type hypersensitivity - dermatitis - dinitrofluorobenzene

References

• 1 Hurry J B. The woad plant and its dye. London; Oxford University Press 1930: p 8-23
• 2 Tang W, Eisenbrand G. Chinese drugs of plant origin. Berlin; Springer-Verlag; 1992: p 805-8
• 3 Hamburger M. Isatis tinctoria - from the rediscovery of an ancient medicinal plant towards a novel anti-inflammatory phytopharmaceutical.  Phytochem Rev. 2002;  1 333-44
• 4 Danz H, Stoyanova S, Wippich P, Brattström A, Hamburger M. Identification and isolation of the cyclooxygenase-2 inhibitory principle in Isatis tinctoria .  Planta Med. 2001;  67 411-6
• 5 Danz H, Stoyanova S, Thomet O AM, Simon H U, Dannhardt G, Ulbrich H. et al . Inhibitory activity of tryptanthrin on prostaglandin and leukotriene synthesis.  Planta Med. 2002;  68 875-80
• 6 Ishihara T, Kohno K, Ushio S, Iwaki K, Ikeda M, Kurimoto M. Tryptanthrin inhibits nitric oxide and prostaglandin E2 synthesis by murine macrophages.  Eur J Pharmacol. 2000;  407 197-204
• 7 Oberthür C, Hamburger M. Tryptanthrin content in Isatis tinctoria leaves - a comparative study of selected strains and post-harvest treatments.  Planta Med. 2004;  70 642-5
• 8 Oberthür C, Schneider B, Graf H, Hamburger M. The elusive indigo precursors in woad (Isatis tinctoria L.) - identification of the major indigo precursor, isatan A, and a structure revision of isatan B.  Chem Biodivers. 2004;  1 174-82
• 9 Oberthür C, Graf H, Hamburger M. The content of indigo precursors in Isatis tinctoria leaves - a comparative study of selected accessions and post-harvest treatments.  Phytochemistry. 2004;  65 3261-8
• 10 Wu X Y, Liu Y, Sheng W, Sun J, Qin G. Chemical constituents of Isatis indigotica .  Planta Med. 1997;  63 55-7
• 11 Rüster G U, Hoffmann B, Hamburger M. Inhibitory activity of indolin-2-one derivatives on compound 48/80-induced histamine release from mast cells.  Pharmazie. 2004;  59 236-7
• 12 Oberthür C, Jäggi U, Hamburger M. HPLC based activity profiling for 5-lipoxygenase inhibitory activity in Isatis tinctoria leaf extracts.  Fitoterapia. 2005;  76 324-32
• 13 Heinemann C, Schliemann-Willers S, Oberthür C, Hamburger M, Elsner P. Prevention of experimentally induced irritant contact dermatitis by extracts of Isatis tinctoria compared to pure tryptanthrin and its impact on UVB-induced erythema.  Planta Med. 2004;  70 385-90
• 14 Danz H, Baumann D, Hamburger M. Quantitative determination of the dual COX-2/5-LOX inhibitor tryptanthrin in Isatis tinctoria by ESI-LC-MS.  Planta Med. 2002;  68 152-7
• 15 Hoessel R, Leclerc S, Endicott J A, Nobel M EM, Lawrie A, Tunnah P. et al . Indirubin, the active constituent of a Chinese antileukemia medicine, inhibits cyclin-dependent kinases.  Nat Cell Biol. 1999;  1 60-7
• 16 Benthin B, Danz H, Hamburger M. Pressurized liquid extraction (PLE) of medicinal plants.  J Chromatogr A. 1999;  837 211-9
• 17 Giner R M, Villalba M, Recio M C, Máñez S, Cerdá-Nicolás M, Ríos J L. Anti-inflammatory glycoterpenoids from Scrophularia auriculata .  Eur J Pharmacol. 2000;  389 243-52
• 18 Góngora L, Máñez S, Giner R M, Recio M C, Ríos J L. On the activity of trifluoperazine and palmitoylcarnitine in mice: delayed hypersensitivity models.  Life Sci. 2000;  66 183-8
• 19 Atta-ur-Rahman , Choudhary M I, Thomsen W J. Bioassay techniques for drug development. Amsterdam; Harwood Academic Publishers 2001: p 100
• 20 Stanley P L, Steiner S, Havens M, Tramposch K M. Mouse skin inflammation induced by multiple topical applications of 12-O-tetradecanoylphorbol 13-acetate.  Skin Pharmacol. 1991;  4 262-71
• 21 Kimber I, Dearman R J. Allergic contact dermatitis: the cellular effectors.  Contact Dermatitis. 2002;  46 1-5
• 22 Young J M, De Young L M. Cutaneous models of inflammation for the evaluation of topical and systemic pharmacological agents. In: Spector J, Back N, editors Pharmacological methods in the control of inflammation. New York; Alan R. Liss 1989: p 215-31
• 23 Polychromopoulos P, Magiatis P, Skaltsounis A L, Myrianthopoulos V, Mikros E, Tarricone A. et al . Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases.  J Med Chem. 2004;  47 935-46
• 24 Kunikata T, Tatefuji T, Aga H, Iwaki K, Ikeda M, Kurimoto M. Indirubin inhibits inflammatory reactions in delayed-type hypersensitivity.  Eur J Pharmacol. 2000;  410 93-100
• 25 Oberthür C, Heinemann C, Elsner P, Benfeldt E, Hamburger M. A comparative study on the skin penertration of pure tryptanthrin and tryptanthrin in Isatis tinctoria extract by dermal microdialysis coupled isotope dilution ESI-LC-MS.  Planta Med. 2003;  69 385-9
• 26 Schliemann-Willers S, Wigger-Alberti W, Kleesz P, Grieshaber R, Elsner P. Natural vegetable fats in the prevention of irritant contact dermatitis.  Contact Dermatitis. 2002;  46 6-12
• 27 Goh C L. Nonoccupational contact dermatitis.  Clin Dermatol. 1998;  16 119-27
• 28 Ross R, Reske-Kunz A B. The role of NO in contact hypersensitivity.  Int Immunopharmacol. 2001;  1 1469-78
• 29 Sedgwick A D, Willoughby D A. Initiation of the inflammatory response and its prevention. In: Bonta IL, Bray MA, Parnham MJ, editors Handbook of inflammation. The pharmacology of inflammation. Amsterdam; Elsevier 1985: p 27-45