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DOI: 10.1055/a-0835-6806
Anti-Inflammatory Effect of a Novel Topical Herbal Composition (VEL-091604) Consisting of Gentian Root, Licorice Root and Willow Bark Extract
Publication History
received 21 November 2018
revised 08 January 2019
accepted 13 January 2019
Publication Date:
28 January 2019 (online)
![](https://www.thieme-connect.de/media/plantamedica/201907/lookinside/thumbnails/10-1055-a-0835-6806_pmc0896-1.jpg)
Abstract
The anti-inflammatory properties of the topical herbal composition VEL-091604 with gentian root, licorice root, and willow bark extract were assessed in a randomized, prospective, placebo-controlled, double-blind ultraviolet (UV)-erythema test study with 42 healthy volunteers in comparison to 1% hydrocortisone acetate. The efficacy and tolerability of VEL-091604 cream 2 times daily over 2 wk was evaluated in an open-label, prospective proof of concept study in 10 subjects with atopic dermatitis using a lesional SCORAD severity score. In the UV-erythema test VEL-091604 cream significantly reduced inflammation compared to placebo and was as effective as 1% hydrocortisone acetate. The clinical study with atopic subjects revealed a significant and rapid reduction of the lesional SCORAD severity score in the test areas after 1 and 2 wk. No adverse events were recorded. It is concluded that the herbal cream VEL-091604 with licorice root, willow bark, and gentian root extract display anti-inflammatory properties in vivo. It is a promising new treatment option for atopic dermatitis that warrants further investigation in controlled studies.
Key words
Glycyrrhiza uralensis - Fabaceae - Salix daphnoides - Salicaceae - Gentiana lutea - Gentianaceae - UV-erythema test - atopic dermatitis* These authors contributed equally.
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References
- 1 Weidinger S, Novak N. Atopic dermatitis. Lancet 2016; 387: 1109-1122
- 2 Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, Goudie DR, Sandilands A, Campbell LE, Smith FJ, OʼRegan GM, Watson RM, Cecil JE, Bale SJ, Compton JG, DiGiovanna JJ, Fleckman P, Lewis-Jones S, Arseculeratne G, Sergeant A, Munro CS, El Houate B, McElreavey K, Halkjaer LB, Bisgaard H, Mukhopadhyay S, McLean WH. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006; 38: 441-446
- 3 Weidinger S, Illig T, Baurecht H, Irvine AD, Rodriguez E, Diaz-Lacava A, Klopp N, Wagenpfeil S, Zhao Y, Liao H, Lee SP, Palmer CN, Jenneck C, Maintz L, Hagemann T, Behrendt H, Ring J, Nothen MM, McLean WH, Novak N. Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations. J Allergy Clin Immunol 2006; 118: 214-219
- 4 Werfel T, Heratizadeh A, Aberer W, Ahrens F, Augustin M, Biedermann T, Diepgen T, Fölster-Holst R, Gieler U, Kahle J, Kapp A, Nast A, Nemat K, Ott H, Przybilla B, Roecken M, Schlaeger M, Schmid-Grendelmeier P, Schmitt J, Schwennesen T, Staab D, Worm M. S2k guideline on diagnosis and treatment of atopic dermatitis – short version. J Dtsch Dermatol Ges 2016; 14: 92-106
- 5 Wollenberg A, Reitamo S, Atzori F, Lahfa M, Ruzicka T, Healy E, Giannetti A, Bieber T, Vyas J, Deleuran M. European Tacrolimus Ointment Study Group. Proactive treatment of atopic dermatitis in adults with 0.1 % tacrolimus ointment. Allergy 2008; 63: 742-750
- 6 Thaçi D, Reitamo S, Gonzalez Ensenat MA, Moss C, Boccaletti V, Cainelli T, van der Valk P, Buckova H, Sebastian M, Schuttelaar ML, Ruzicka T. European Tacrolimus Ointment Study Group. Proactive disease management with 0.03 % tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study. Br J Dermatol 2008; 159: 1348-1356
- 7 Blauvelt A, de Bruin-Weller M, Gooderham M, Cather JC, Weisman J, Pariser D, Simpson EL, Papp KA, Hong HC, Rubel D, Foley P, Prens E, Griffiths CEM, Etoh T, Pinto PH, Pujol RM, Szepietowski JC, Ettler K, Kemény L, Zhu X, Akinlade B, Hultsch T, Mastey V, Gadkari A, Eckert L, Amin N, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD, Shumel B. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet 2017; 389: 2287-2303
- 8 Czarnowicki T, Krueger JG, Guttman-Yassky E. Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march. J Allergy Clin Immunol 2017; 139: 1723-1734
- 9 Vieira BL, Lim NR, Lohman ME, Lio PA. Complementary and alternative medicine for atopic dermatitis: an evidence-based review. Am J Clin Dermatol 2016; 17: 557-581
- 10 Schempp CM, Windeck T, Hezel S, Simon JC. Topical treatment of atopic dermatitis with St. Johnʼs wort cream – a randomized, placebo controlled, double blind half-side comparison. Phytomedicine 2003; 10 (Suppl. 04) 31-37
- 11 Wölfle U, Seelinger G, Schempp CM. Topical application of St. Johnʼs Wort (Hypericum perforatum). Planta Med 2014; 80: 109-120
- 12 Hoffmann J, Wölfle U, Schempp CM, Casetti F. Tannins from Potentilla officinalis display anti-inflammatory effects in the UV-erythema test and on atopic skin. J Dtsch Dermatol Ges 2016; 14: 917-922
- 13 Saeedi M, Morteza-Semnani K, Ghoreishi MR. The treatment of atopic dermatitis with licorice gel. J Dermatolog Treat 2003; 14: 153-157
- 14 Abramovits W, Boguniewicz M. Adult Atopiclair Study Group. A multicenter, randomized, vehicle-controlled clinical study to examine the efficacy and safety of MAS063DP (Atopiclair) in the management of mild to moderate atopic dermatitis in adults. J Drugs Dermatol 2006; 5: 236-244
- 15 Boguniewicz M, Zeichner JA, Eichenfield LF, Hebert AA, Jarratt M, Lucky AW, Paller AS. MAS063DP is an effective monotherapy for mild to moderate atopic dermatitis in infants and children: a multicenter, randomized, vehicle-controlled study. J Pediatr 2008; 152: 854-859
- 16 Luger T, Loske KD, Elsner P, Kapp A, Kerscher M, Korting HC, Krutmann J, Niedner R, Röcken M, Ruzicka T, Schwarz T. Topical skin therapy with glucocorticoids – therapeutic index. J Dtsch Dermatol Ges 2004; 2: 629-634
- 17 Yang R, Wang LQ, Yuan BC, Liu Y. The pharmacological activities of licorice. Planta Med 2015; 81: 654-669
- 18 Lee YM, Hirota S, Jippo-Kanemoto T, Kim HR, Shin TY, Yeom Y, Lee KK, Kitamura Y, Nomura S, Kim HM. Inhibition of histamine synthesis by glycyrrhetinic acid in mast cells cocultured with Swiss 3T3 fibroblasts. Int Arch Allergy Immunol 1996; 110: 272-277
- 19 Afnan Q, Adil MD, Nissar-Ul A, Rafiq AR, Amir HF, Kaiser P, Gupta VK, Vishwakarma R, Tasduq SA. Glycyrrhizic acid (GA), a triterpenoid saponin glycoside alleviates ultraviolet-B irradiation-induced photoaging in human dermal fibroblasts. Phytomedicine 2012; 19: 658-664
- 20 Farrukh MR, Nissar UA, Kaiser PJ, Afnan Q, Sharma PR, Bhushan S, Tasduq SA. Glycyrrhizic acid (GA) inhibits reactive oxygen species mediated photodamage by blocking ER stress and MAPK pathway in UV-B irradiated human skin fibroblasts. J Photochem Photobiol B 2015; 148: 351-357
- 21 Yu H, Li H, Li Y, Li M, Chen G. Effect of isoliquiritigenin for the treatment of atopic dermatitis-like skin lesions in mice. Arch Dermatol Res 2017; 309: 805-813
- 22 Kühnl J, Roggenkamp D, Gehrke SA, Stäb F, Wenck H, Kolbe L, Neufang G. Licochalcone A activates Nrf2 in vitro and contributes to licorice extract-induced lowered cutaneous oxidative stress in vivo . Exp Dermatol 2015; 24: 42-47
- 23 Song NR, Kim JE, Park JS, Kim JR, Kang H, Lee E, Kang YG, Son JE, Seo SG, Heo YS, Lee KW. Licochalcone A, a polyphenol present in licorice, suppresses UV-induced COX-2 expression by targeting PI3K, MEK1, and B-Raf. Int J Mol Sci 2015; 16: 4453-4470
- 24 Sulzberger M, Worthmann AC, Holtzmann U, Buck B, Jung KA, Schoelermann AM, Rippke F, Stäb F, Wenck H, Neufang G, Grönniger E. Effective treatment for sensitive skin: 4-t-butylcyclohexanol and licochalcone A. J Eur Acad Dermatol Venereol 2016; 30 (Suppl. 01) 9-17
- 25 Gafner S, Bergeron C, Villinski JR, Godejohann M, Kessler P, Cardellina JH, Ferreira D, Feghali K, Grenier D. Isoflavonoids and coumarins from Glycyrrhiza uralensis: antibacterial activity against oral pathogens and conversion of isoflavans into isoflavan-quinones during purification. J Nat Prod 2011; 74: 2514-2519
- 26 Villinski JR, Bergeron C, Cannistra JC, Gloer JB, Coleman CM, Ferreira D, Azelmat J, Grenier D, Gafner S. Pyrano-isoflavans from Glycyrrhiza uralensis with antibacterial activity against Streptococcus mutans and Porphyromonas gingivalis . J Nat Prod 2014; 77: 521-526
- 27 Bassino E, Gasparri F, Munaron L. Pleiotropic effects of white willow bark and 1,2-decanediol on human adult keratinocytes. Skin Pharmacol Physiol 2018; 31: 10-18
- 28 Gopaul R, Knaggs HE, Lephart JF, Holley KC, Gibson EM. An evaluation of the effect of a topical product containing salicin on the visible signs of human skin aging. J Cosmet Dermatol 2010; 9: 196-201
- 29 Wölfle U, Elsholz FA, Kersten A, Haarhaus B, Müller WE, Schempp CM. Expression and functional activity of the bitter taste receptors TAS2R1 and TAS2R38 in human keratinocytes. Skin Pharmacol Physiol 2015; 28: 137-146
- 30 Wölfle U, Haarhaus B, Seiwerth J, Cawelius A, Schwabe K, Quirin KW, Schempp CM. The herbal bitter drug Gentiana lutea modulates lipid synthesis in human keratinocytes in vitro and in vivo . Int J Mol Sci 2017; 18: 1814
- 31 Wölfle U, Haarhaus B, Schempp CM. Amarogentin displays immunomodulatory effects in human mast cells and keratinocytes. Med Inflamm 2015; 2015: 630128
- 32 Öztürk N, Korkmaz S, Öztürk Y, Baser KHC. Effects of gentiopicroside, sweroside and swertiamarine, secoiridoids from gentian (Gentiana lutea ssp. symphyandra), on cultured chicken embryonic fibroblasts. Planta Med 2006; 72: 289-294
- 33 Jocher A, Kessler S, Hornstein S, Schulte Mönting J, Schempp CM. The UV-erythema test as a model to investigate the anti-inflammatory potentency of topical preparations – reevaluation and optimization of the method. Skin Pharmacol Physiol 2005; 18: 234-240
- 34 Reuter J, Jocher A, Hornstein S, Mönting JS, Schempp CM. Sage extract rich in phenolic diterpenes inhibits ultraviolet-induced erythema in vivo . Planta Med 2007; 73: 1190-1191
- 35 Diepgen TL, Fartasch M, Hornstein OP. Kriterien zur Beurteilung der atopischen Hautdiathese. Dermatosen 1991; 39: 79-83