Experimental Study of Therapeutic Efficacy of the Topical Preparation «Kourochitin» in Skin Allergy

Author(s): Anna Anatolievna Klimovich*, Olga Nikolaevna Styshova, Alexander Mikhailovich Popov, Tatiana Vladimirovna Moskvina*, Alexander Vasilevich Tsybulsky, Dmitry Albertovich Derunov, Valentin Aronovich Stonik

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 10 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: The researchers of PIBOC RAS developed the dermo-protective topical drug called «Kourochitin», active substance of which is known quinazoline alkaloid tryptanthrin. In the present work, therapeutic efficacy of this drug in the treatment of allergic dermatosis was evaluated.

Methods: Dermo-protective action of «Kourochitin» was studied in tow murine models: 2, 4- dinitrofluorobenzene- induced allergic contact dermatitis (ACD) and imiquimod-induced psoriasis.

Results and Discussion: In a model ACD, it was shown that «Kourochitin» exhibits the curative action on pathophysiological, hematological and immunological parameters in ACD. Namely, «Kourochitin» 1) reduces the level of erythema in the allergen damaged skin area and increases the healing index of the epidermis; 2) normalizes the content of eosinophils, basophils and monocytes in the blood of experimental animals; 3) inhibits the production of main pro-inflammatory cytokines: interleukins - 1 and 2, interferon-gamma, and granulocyte-macrophage colony-stimulating factor. In a murine model of imiquimod-induced psoriasis, it was shown that «Kourochitin» application led to reduction in psoriasis severity on the inflamed epidermis of experimental animals. Additionally, in veterinary research, «Kourochitin»-treatment of canine atopic dermatitis almost completely eliminated signs of allergic manifestations on the epidermis.

Conclusion: The obtained data suggest that «Kourochitin» as anti-inflammatory, anti-allergic, and wound healing remedy is a potential drug for therapy of various dermatological diseases, in particular allergic skin lesions.

Keywords: Tryptanthrin, quinazoline alkaloids, drug development, dermatoprotective drugs, skin allergy, anti-inflammatory remedies.

[1]
Fonacier, L.S.; Dreskin, S.C.; Leung, D.Y. Allergic skin diseases. J. Allergy Clin. Immunol., 2010, 125(Suppl. 2), S138-S149.
[http://dx.doi.org/10.1016/j.jaci.2009.05.039] [PMID: 19932921]
[2]
Popov, A.M.; Krivoshapko, O.N.; Tsybulsky, A.V.; Shtoda, Y.P.; Klimovich, A.A.; Gafurov, Y.M.; Artyukov, A.A. Therapeutic activity of preparation «Kourochitin» at modeling allergic dermatitis. Rus. J. Biopharm., 2015, 7, 24-30.
[3]
Yu, B.; Dai, L.; Chen, J.; Sun, W.; Chen, J.; Du, L.; Deng, N.; Chen, D. Prenatal and neonatal factors involved in the development of childhood allergic diseases in Guangzhou primary and middle school students. BMC Pediatr., 2019, 19(1), 479.
[http://dx.doi.org/10.1186/s12887-019-1865-0] [PMID: 31810445]
[4]
Klimek, L.; Sperl, A. [Evidence-based treatment options for allergic diseases in otolaryngology: an update]. HNO, 2013, 61(6), 525-538.
[http://dx.doi.org/10.1007/s00106-013-2709-0] [PMID: 23712364]
[5]
Stahn, C.; Buttgereit, F. Genomic and nongenomic effects of glucocorticoids. Nat. Clin. Pract. Rheumatol., 2008, 4(10), 525-533.
[http://dx.doi.org/10.1038/ncprheum0898] [PMID: 18762788]
[6]
Jahng, Y. Progress in the studies on tryptanthrin, an alkaloid of history. Arch. Pharm. Res., 2013, 36(5), 517-535.
[http://dx.doi.org/10.1007/s12272-013-0091-9] [PMID: 23543631]
[7]
Zhang, X.; Xia, J.; Zhang, W.; Luo, Y.; Sun, W.; Zhou, W. Study on pharmacokinetics and tissue distribution of single dose oral tryptanthrin in Kunming mice by validated reversed-phase high-performance liquid chromatography with ultraviolet detection. Integr. Med. Res., 2017, 6(3), 269-279.
[http://dx.doi.org/10.1016/j.imr.2017.05.001] [PMID: 28951841]
[8]
Wagner-Döbler, I.; Rheims, H.; Felske, A.; El-Ghezal, A.; Flade-Schröder, D.; Laatsch, H.; Lang, S.; Pukall, R.; Tindall, B.J. Oceanibulbus indolifex gen. nov., sp. nov., a North Sea alphaproteobacterium that produces bioactive metabolites. Int. J. Syst. Evol. Microbiol., 2004, 54(Pt 4), 1177-1184.
[http://dx.doi.org/10.1099/ijs.0.02850-0] [PMID: 15280288]
[9]
Popov, A.M.; Shtoda, Y.P.; Krivoshapko, O.N.; Gafurov, Y.M.; Moskovkina, T.V. Wound healing activity of different ointment forms of quinazoline alkaloid triptanthrin. Rus. J. Biopharm., 2012, 4, 21-24.
[10]
Kaur, R.; Manjal, S.K.; Rawal, R.K.; Kumar, K. Recent synthetic and medicinal perspectives of tryptanthrin. Bioorg. Med. Chem., 2017, 25(17), 4533-4552.
[http://dx.doi.org/10.1016/j.bmc.2017.07.003] [PMID: 28720329]
[11]
Kawakami, J.; Matsushima, N.; Ogawa, Y. Antibacterial and antifungal activities of tryptanthrin derivatives. Trans. Mater. Res. Soc. Jpn., 2011, 36, 603-606.
[http://dx.doi.org/10.14723/tmrsj.36.603]
[12]
Pathania, A.S.; Kumar, S.; Guru, S.K.; Bhushan, S.; Sharma, P.R.; Aithagani, S.K.; Singh, P.P.; Vishwakarma, R.A.; Kumar, A.; Malik, F. The synthetic tryptanthrin analogue suppresses STAT3 signaling and induces caspase dependent apoptosis via ERK up regulation in human leukemia HL-60 cells. PLoS One, 2014, 9(11), e110411
[http://dx.doi.org/10.1371/journal.pone.0110411] [PMID: 25383546]
[13]
Vlachos, C.; Schulte, B.M.; Magiatis, P.; Adema, G.J.; Gaitanis, G. Malassezia-derived indoles activate the aryl hydrocarbon receptor and inhibit toll-like receptor-induced maturation in monocyte-derived dendritic cells. Br. J. Dermatol., 2012, 167(3), 496-505.
[http://dx.doi.org/10.1111/j.1365-2133.2012.11014.x] [PMID: 22533375]
[14]
Wang, Z.; Wu, X.; Wang, C.L.; Wang, L.; Sun, C.; Zhang, D.B.; Liu, J.L.; Liang, Y.N.; Tang, D.X.; Tang, Z.S. Tryptanthrin protects mice against dextran sulfate sodium-induced colitis through inhibition of TNF-α/NF-κB and IL-6/STAT3 pathways. Molecules, 2018, 23(5), E1062
[http://dx.doi.org/10.3390/molecules23051062] [PMID: 29724065]
[15]
Ishihara, T.; Kohno, K.; Ushio, S.; Iwaki, K.; Ikeda, M.; Kurimoto, M. Tryptanthrin inhibits nitric oxide and prostaglandin E(2) synthesis by murine macrophages. Eur. J. Pharmacol., 2000, 407(1-2), 197-204.
[http://dx.doi.org/10.1016/S0014-2999(00)00674-9] [PMID: 11050308]
[16]
Danz, H.; Stoyanova, S.; Thomet, O.A.; Simon, H.U.; Dannhardt, G.; Ulbrich, H.; Hamburger, M. Inhibitory activity of tryptanthrin on prostaglandin and leukotriene synthesis. Planta Med., 2002, 68(10), 875-880.
[http://dx.doi.org/10.1055/s-2002-34922] [PMID: 12391548]
[17]
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(2), 152-157.
[http://dx.doi.org/10.1055/s-2002-20252] [PMID: 11859467]
[18]
Pergola, C.; Jazzar, B.; Rossi, A.; Northoff, H.; Hamburger, M.; Sautebin, L.; Werz, O. On the inhibition of 5-lipoxygenase product formation by tryptanthrin: Mechanistic studies and efficacy in vivo. Br. J. Pharmacol., 2012, 165(3), 765-776.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01605.x] [PMID: 21797843]
[19]
Han, N.R.; Moon, P.D.; Kim, H.M.; Jeong, H.J. Tryptanthrin ameliorates atopic dermatitis through down-regulation of TSLP. Arch. Biochem. Biophys., 2014, 542, 14-20.
[http://dx.doi.org/10.1016/j.abb.2013.11.010] [PMID: 24295961]
[20]
Takei, Y.; Kunikata, T.; Aga, M.; Inoue, S.; Ushio, S.; Iwaki, K.; Ikeda, M.; Kurimoto, M. Tryptanthrin inhibits interferon-gamma production by Peyer’s patch lymphocytes derived from mice that had been orally administered staphylococcal enterotoxin. Biol. Pharm. Bull., 2003, 26(3), 365-367.
[http://dx.doi.org/10.1248/bpb.26.365] [PMID: 12612449]
[21]
Hernandez-Santana, Y.E.; Giannoudaki, E.; Leon, G.; Lucitt, M.B.; Walsh, P.T. Current perspectives on the interleukin-1 family as targets for inflammatory disease. Eur. J. Immunol., 2019, 49(9), 1306-1320.
[http://dx.doi.org/10.1002/eji.201848056] [PMID: 31250428]
[22]
Cheng, H.M.; Wu, Y-C.; Wang, Q.; Song, M.; Wu, J.; Chen, D.; Li, K.; Wadman, E.; Kao, S.T.; Li, T.C.; Leon, F.; Hayden, K.; Brodmerkel, C.; Chris Huang, C. Clinical efficacy and IL-17 targeting mechanism of Indigo naturalis as a topical agent in moderate psoriasis. BMC Complement. Altern. Med., 2017, 17(1), 439.
[http://dx.doi.org/10.1186/s12906-017-1947-1] [PMID: 28865459]
[23]
Gaitanis, G.; Magiatis, P.; Hantschke, M.; Bassukas, I.D.; Velegraki, A. The Malassezia genus in skin and systemic diseases. Clin. Microbiol. Rev., 2012, 25(1), 106-141.
[http://dx.doi.org/10.1128/CMR.00021-11] [PMID: 22232373]
[24]
Hay, R.J. Malassezia, dandruff and seborrhoeic dermatitis: An overview. Br. J. Dermatol., 2011, 165(Suppl. 2), 2-8.
[http://dx.doi.org/10.1111/j.1365-2133.2011.10570.x] [PMID: 21919896]
[25]
Mexia, N.; Koutrakis, S.; He, G.; Skaltsounis, A.L.; Denison, M.S.; Magiatis, P. One-Step transformation of simple indolic compounds to Malassezia-related alkaloids with high AhR potency and efficacy. Chem. Res. Toxicol., 2019, 32(11), 2238-2249.
[http://dx.doi.org/10.1021/acs.chemrestox.9b00270] [PMID: 31647221]
[26]
Hwang, J.M.; Oh, T.; Kaneko, T.; Upton, A.M.; Franzblau, S.G.; Ma, Z.; Cho, S.N.; Kim, P. Design, synthesis, and structure-activity relationship studies of tryptanthrins as antitubercular agents. J. Nat. Prod., 2013, 76(3), 354-367.
[http://dx.doi.org/10.1021/np3007167] [PMID: 23360475]
[27]
Popov, A.M.; Nedashkovskaya, O.I.; Gafurov, Y.M.; Moskovkina, T.V. Antimicrobial activity of «Kourochitin» preparation. Russ. J. Biopharm, 2011, 3, 19-22.
[28]
Honda, G.; Tabata, M.; Tsuda, M. The antimicrobial specificity of tryptanthrin. Planta Med., 1979, 37(2), 172-174.
[http://dx.doi.org/10.1055/s-0028-1097320] [PMID: 515225]
[29]
Moskovkina, T.V.; Denisenko, M.V.; Kalinovskii, A.I.; Stonik, V.A. Synthesis of substituted tryptanthrins via oxidation of isatin and its derivatives. Russ. J. Org. Chem., 2013, 49, 1740-1743.
[http://dx.doi.org/10.1134/S1070428013120051]
[30]
Moskovkina, T.V.; Kalinovskii, A.I.; Makhankov, V.V. Synthesis of tryptanthrin (couroupitine) derivatives by reaction of substituted isatins with phosphoryl chloride. Russ. J. Org. Chem., 2012, 48, 123-126.
[http://dx.doi.org/10.1134/S1070428012010204]
[31]
Yuan, X.Y.; Liu, W.; Zhang, P.; Wang, R.Y.; Guo, J.Y. Effects and mechanisms of aloperine on 2, 4-dinitrofluorobenzene-induced allergic contact dermatitis in BALB/c mice. Eur. J. Pharmacol., 2010, 629(1-3), 147-152.
[http://dx.doi.org/10.1016/j.ejphar.2009.12.007] [PMID: 20006963]
[32]
Zhao, J.; Di, T.; Wang, Y.; Wang, Y.; Liu, X.; Liang, D.; Li, P. Paeoniflorin inhibits imiquimod-induced psoriasis in mice by regulating Th17 cell response and cytokine secretion. Eur. J. Pharmacol., 2016, 772, 131-143.
[http://dx.doi.org/10.1016/j.ejphar.2015.12.040] [PMID: 26738780]
[33]
Agafonova, I.; Moskovkina, T. Studies on anti-inflammatory action of tryptanthrin, using a model of dss-induced colitis of mice and magnetic resonance imaging. Appl. Magn. Reson., 2015, 46, 781-791.
[http://dx.doi.org/10.1007/s00723-015-0674-3]
[34]
Delneste, Y.; Beauvillain, C.; Jeannin, P. [Innate immunity: Structure and function of TLRs]. Med. Sci. (Paris),, 2007, 23(1), 67-73.
[http://dx.doi.org/10.1051/medsci/200723167] [PMID: 17212934]
[35]
Kim, S.Y.; Heo, S.; Kim, S.H.; Kwon, M.; Sung, N.J.; Ryu, A.R.; Lee, M.Y.; Park, S.A.; Youn, H.S. Suppressive effects of dehydrocostus lactone on the toll-like receptor signaling pathways. Int. Immunopharmacol., 2019., 78106075
[http://dx.doi.org/10.1016/j.intimp.2019.106075] [PMID: 31812722]
[36]
Schrenk, D.; Riebniger, D.; Till, M.; Vetter, S.; Fiedler, H.P. Tryptanthrins: a novel class of agonists of the aryl hydrocarbon receptor. Biochem. Pharmacol., 1997, 54(1), 165-171.
[http://dx.doi.org/10.1016/S0006-2952(97)00150-0] [PMID: 9296363]
[37]
Gutiérrez-Vázquez, C.; Quintana, F.J. Regulation of the immune response by the aryl hydrocarbon receptor. Immunity, 2018, 48(1), 19-33.
[http://dx.doi.org/10.1016/j.immuni.2017.12.012] [PMID: 29343438]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 10
Year: 2020
Published on: 11 October, 2020
Page: [1237 - 1244]
Pages: 8
DOI: 10.2174/1570180817666200316155643
Price: $65

Article Metrics

PDF: 11
HTML: 1