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p-coumaric acid, an active ingredient of Panax ginseng, ameliolates atopic dermatitis-like skin lesions through inhibition of thymic stromal lymphopoietin in mice

  • Moon, Phil-Dong (Center for Converging Humanities, Kyung Hee University) ;
  • Han, Na-Ra (Department of Pharmacology, College of Korean Medicine, Kyung Hee University) ;
  • Lee, Jin Soo (Department of Pharmacology, College of Korean Medicine, Kyung Hee University) ;
  • Kim, Hyung-Min (Department of Pharmacology, College of Korean Medicine, Kyung Hee University) ;
  • Jeong, Hyun-Ja (Division of Food and Pharmaceutical Engineering, BioChip Research Center, Hoseo University)
  • Received : 2020.03.25
  • Accepted : 2020.06.28
  • Published : 2021.01.15

Abstract

Background: Atopic dermatitis (AD) is associated with chronic skin inflammatory reactions. p-coumaric acid (pCA) is an active ingredient of Panax ginseng Meyer (Araliaceae). Methods: Here, we estimated an anti-AD effect of pCA on activated mast cells, activated splenocytes, and a mouse model of AD. Cytokines levels were measured by ELISA and protein activation was analyzed by Western blotting. 2,4-dinitrofluorobenzene (DNFB) was used to induce AD-like skin lesions. Results: The treatment with pCA suppressed the productions and mRNA expressions of thymic stromal lymphopoietin (TSLP), TNF-α, IL-6, and IL-1β in HMC-1 cells. pCA downregulated the expressions of RIP2 and caspase-1, phosphorylated-(p)p38/pJNK/pERK, and pIKKβ/pIkBα/NF-κB in HMC-1 cells. pCA also decreased the productions of TSLP, TNF-α, IL-6, IL-4, and IFN-γ in the supernatant of stimulated splenic cells. Comparing to DNFB-sensitized control group, pCA-treated group alleviated pathological changes of AD-like lesions. pCA decreased the proteins and mRNA expressions levels of TSLP, IL-6, and IL-4 in the skin lesions. Caspase-1 activation was also downregulated by pCA treatment in the AD-like lesions. The serum levels of histamine, IgE, TSLP, TNF-α, IL-6, and IL-4 were suppressed following treatment with pCA. Conclusion: This study suggests that pCA has the potential to improve AD by suppressing TSLP as well as inflammatory cytokines via blocking of caspase-1/NF-κB signal cascade.

Keywords

References

  1. Yosipovitch G, Reaney M, Mastey V, Eckert L, Abbe A, Nelson L, Clark M, Williams N, Chen Z, Ardeleanu M, et al. Peak pruritus numerical rating scale: psychometric validation and responder definition for assessing itch in moderate-to-severe atopic dermatitis. Br J Dermatol 2019;181:761-9. https://doi.org/10.1111/bjd.17744
  2. Mohn CH, Blix HS, Halvorsen JA, Nafstad P, Valberg M, Lagerlov P. Incidence trends of atopic dermatitis in infancy and early childhood in a nationwide prescription registry study in Norway. JAMA Netw Open 2018;1:e184145. https://doi.org/10.1001/jamanetworkopen.2018.4145
  3. Yoo J, Omori M, Gyarmati D, Zhou B, Aye T, Brewer A, Comeau MR, Campbell DJ, Ziegler SF. Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin. J Exp Med 2005;202:541-9. https://doi.org/10.1084/jem.20041503
  4. Moon PD, Han NR, Kim HM, Jeong HJ. High-fat diet exacerbates dermatitis through up-regulation of TSLP. J Invest Dermatol 2019;68:467-74.
  5. Zhu Y, Pan WH, Wang XR, Liu Y, Chen M, Xu XG, Liao WQ, Hu JH. Tryptase and protease-activated receptor-2 stimulate scratching behavior in a murine model of ovalbumin-induced atopic-like dermatitis. Int Immunopharmacol 2015;28:507-12. https://doi.org/10.1016/j.intimp.2015.04.047
  6. Han NR, Oh HA, Nam SY, Moon PD, Kim DW, Kim HM, Jeong HJ. TSLP induces mast cell development and aggravates allergic reactions through the activation of MDM2 and STAT6. J Invest Dermatol 2014;134:2521-30. https://doi.org/10.1038/jid.2014.198
  7. Han NR, Moon PD, Yoou MS, Chang TS, Kim HM, Jeong HJ. Effect of massage therapy by VOSKIN 125+ painkiller® on inflammatory skin lesions. Dermatol Ther 2018;31:e12628. https://doi.org/10.1111/dth.12628
  8. Schneider C, Docke WD, Zollner TM, Rose L. Chronic mouse model of TMAinduced contact hypersensitivity. J Invest Dermatol 2009;129:899-907. https://doi.org/10.1038/jid.2008.307
  9. Han NR, Moon PD, Kim NR, Kim HY, Jeong HJ, Kim HM. Schisandra chinensis and its main constituent schizandrin attenuate allergic reactions by downregulating caspase-1 in ovalbumin-sensitized mice. Am J Chin Med 2017;45:159-72. https://doi.org/10.1142/S0192415X17500112
  10. Schneider KS, GroB CJ, Dreier RF, Saller BS, Mishra R, Gorka O, Heilig R, Meunier E, Dick MS, Cikovic T, et al. The inflammasome drives GSDMD-independent secondary pyroptosis and IL-1 release in the absence of caspase-1 protease activity. Cell Rep 2017;21:3846-59. https://doi.org/10.1016/j.celrep.2017.12.018
  11. Blazejewski AJ, Thiemann S, Schenk A, Pils MC, GalveZ EJC, Roy U, Heise U, de Zoete MR, Flavell RA, Strowig T. Microbiota normalization reveals that canonical caspase-1 activation exacerbates chemically induced intestinal inflammation. Cell Rep 2017;19:2319-30. https://doi.org/10.1016/j.celrep.2017.05.058
  12. Moon PD, Kim HM. Thymic stromal lymphopoietin is expressed and produced by caspase-1/NF-κB pathway in mast cells. Cytokine 2011;54:239-43. https://doi.org/10.1016/j.cyto.2011.03.007
  13. Cha H, Lee S, Lee JH, Park JW. Protective effects of p-coumaric acid against acetaminophen-induced hepatotoxicity in mice. Food Chem Toxicol 2018;121:131-9. https://doi.org/10.1016/j.fct.2018.08.060
  14. Lim JY, Ishiguro K, Kubo I. Tyrosinase inhibitory p-coumaric acid from ginseng leaves. Phytother Res 1999;13:371-5. https://doi.org/10.1002/(SICI)1099-1573(199908/09)13:5<371::AID-PTR453>3.0.CO;2-L
  15. Chung IM, Lim JJ, Ahn MS, Jeong HN, An TJ, Kim SH. Comparative phenolic compound profiles and antioxidative activity of the fruit, leaves, and roots of Korean ginseng (Panax ginseng Meyer) according to cultivation years. J Ginseng Res 2016;40:68-75. https://doi.org/10.1016/j.jgr.2015.05.006
  16. Lee JI, Park KS, Cho IH. Panax ginseng: a candidate herbal medicine for autoimmune disease. J Ginseng Res 2019;43:342-8. https://doi.org/10.1016/j.jgr.2018.10.002
  17. Long R, Li T, Tong C, Wu L, Shi S. Molecularly imprinted polymers coated CdTe quantum dots with controllable particle size for fluorescent determination of p-coumaric acid. Talanta 2019;196:579-84. https://doi.org/10.1016/j.talanta.2019.01.007
  18. Lorz LR, Kim MY, Cho JY. Medicinal potential of Panax ginseng and its ginsenosides in atopic dermatitis treatment. J Ginseng Res 2020;44:8-13. https://doi.org/10.1016/j.jgr.2018.12.012
  19. Kim W, Lim D, Kim J. p-Coumaric acid, a major active compound of bambusae caulis in taeniam, suppresses cigarette smoke-induced pulmonary inflammation. Am J Chin Med 2018;46:407-21. https://doi.org/10.1142/s0192415x18500209
  20. Chen X, Murakami T, Oppenheim JJ, Howard OMZ. Differential response of murine CD4+CD25+ and CD4+CD25- T cells to dexamethasone-induced cell death. Eur J Immunol 2004;34:859-69. https://doi.org/10.1002/eji.200324506
  21. Moon PD, Kim HM. Anti-inflammatory effect of phenethyl isothiocyanate, an active ingredient of Raphanus sativus Linne. Food Chem 2012;131:1332-9. https://doi.org/10.1016/j.foodchem.2011.09.127
  22. Han NR, Moon PD, Ryu KJ, Jang JB, Kim HM, Jeong HJ. β-eudesmol suppresses allergic reactions via inhibiting mast cell degranulation. Clin Exp Pharmacol Physiol 2017;44:257-65. https://doi.org/10.1111/1440-1681.12698
  23. Han NR, Moon PD, Ryu KJ, Kim NR, Kim HM, Jeong HJ. Inhibitory effect of naringenin via IL-13 level regulation on thymic stromal lymphopoietin-induced inflammatory reactions. Clin Exp Pharmacol Physiol 2018;45:362-9. https://doi.org/10.1111/1440-1681.12880
  24. Han NR, Moon PD, Yoo MS, Ryu KJ, Kim HM, Jeong HJ. Regulatory effects of chrysophanol, a bioactive compound of AST2017-01 in a mouse model of 2,4-dinitrofluorobenzene-induced atopic dermatitis. Int Immunopharmacol 2018;62:220-6. https://doi.org/10.1016/j.intimp.2018.06.046
  25. Moon PD, Han NR, Lee JS, Kim HY, Hong S, Kim HJ, Yoo MS, Kim HM, Jeong HJ. β-eudesmol inhibits thymic stromal lymphopoietin through blockade of caspase-1/NF-κB signal cascade in allergic rhinitis murine model. Chem Biol Interact 2018;294:101-6. https://doi.org/10.1016/j.cbi.2018.08.026
  26. Han NR, Moon PD, Kim HM, Jeong HJ. Cordycepin ameliorates skin inflammation in a DNFB-challenged murine model of atopic dermatitis. Immunopharmacol Immunotoxicol 2018;40:401-7. https://doi.org/10.1080/08923973.2018.1510964
  27. Moon PD, Choi IS, Go JH, Lee BJ, Kang SW, Yoon S, Han SJ, Nam SY, Oh HA, Han NR, et al. Inhibitory effects of BiRyuChe-bang on mast cell-mediated allergic reactions and inflammatory cytokines production. Am J Chin Med 2013;41:1267-82. https://doi.org/10.1142/S0192415X13500857
  28. Klonowska J, Glen J, Nowicki RJ, Trzeciak M. New cytokines in the patho- genesis of atopic dermatitis-new therapeutic targets. Int J Mol Sci 2018;19:3086. https://doi.org/10.3390/ijms19103086
  29. Miller SC, Huang R, Sakamuru S, Shukla SJ, Attene-Ramos MS, Shinn P, Van Leer D, Leister W, Austin CP, Xia M. Identification of known drugs that act as inhibitors of NF-kappaB signaling and their mechanism of action. Biochem Pharmacol 2010;79:1272-80. https://doi.org/10.1016/j.bcp.2009.12.021
  30. Gonzalez J, Orlofsky A, Prystowsky MB. A1 is a growth-permissive antiapoptotic factor mediating postactivation survival in T cells. Blood 2003;101:2679-85. https://doi.org/10.1182/blood-2002-04-1229
  31. van den Eertwegh AJ, Claassen E. T cells in the spleen: localization, cytokine production and cell/cell interactions. Res Immunol 1991;142:334-9. https://doi.org/10.1016/0923-2494(91)90086-X
  32. Ohtsu H, Seike M. Histamine and histamine receptors in allergic dermatitis. Handb Exp Pharmacol 2017;241:333-45. https://doi.org/10.1007/164_2016_9
  33. Moon PD, Han NR, Lee JS, Kim HM, Jeong HJ. Effects of linalyl acetate on thymic stromal lymphopoietin production in mast cells. Molecules 2018;23:E1711.
  34. Oyoshi MK, Venturelli N, Geha RS. Thymic stromal lymphopoietin and IL-33 promote skin inflammation and vaccinia virus replication in a mouse model of atopic dermatitis. J Allergy Clin Immunol 2016;138:283-6. https://doi.org/10.1016/j.jaci.2015.12.1304
  35. Jang H, Matsuda A, Jung K, Karasawa K, Matsuda K, Oida K, Ishizaka S, Ahn G, Amagai Y, Moon C, et al. Skin pH is the master switch of kallikrein 5-mediated skin barrier destruction in a murine atopic dermatitis model. J Invest Dermatol 2016;136:127-35. https://doi.org/10.1038/jid.2015.363
  36. Ziegler SF. The role of thymic stromal lymphopoietin (TSLP) in allergic disorders. Curr Opin Immunol 2010;22:795-9. https://doi.org/10.1016/j.coi.2010.10.020
  37. Szymanski L, Cios A, Lewicki S, Szymanski P, Stankiewicz W. Fas/FasL pathway and cytokines in keratinocytes in atopic dermatitis - manipulation by the electromagnetic field. PLoS One 2018;13:e0205103. https://doi.org/10.1371/journal.pone.0205103
  38. Szegedi K, Lutter R, Res PC, Bos JD, Luiten RM, Kezic S, Middelkamp-Hup MA. Cytokine profiles in interstitial fluid from chronic atopic dermatitis skin. J Eur Acad Dermatol Venereol 2015;29:2136-44. https://doi.org/10.1111/jdv.13160
  39. Batista DI, Perez L, Orfali RL, Zaniboni MC, Samorano LP, Pereira NV, Sotto MN, Ishizaki AS, Oliveira LM, Sato MN, et al. Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1/Th2/Th17 cytokines in adults with atopic dermatitis. J Eur Acad Dermatol Venereol 2015;29:1091-5. https://doi.org/10.1111/jdv.12753
  40. Han NR, Kim HM, Jeong HJ. Thymic stromal lymphopoietin is regulated by the intracellular calcium. Cytokine 2012;59:215-7. https://doi.org/10.1016/j.cyto.2012.04.015
  41. Humke EW, Shriver SK, Starovasnik MA, Fairbrother WJ, Dixit VM. ICEBERG: a novel inhibitor of interleukin-1beta generation. Cell 2000;103:99-111. https://doi.org/10.1016/S0092-8674(00)00108-2
  42. Han NR, Moon PD, Kim HM, Jeong HJ. Tryptanthrin ameliorates atopic dermatitis through down-regulation of TSLP. Arch Biochem Biophys 2014;542:14-20. https://doi.org/10.1016/j.abb.2013.11.010
  43. Moon PD, Choi IH, Kim HM. Naringenin suppresses the production of thymic stromal lymphopoietin through the blockade of RIP2 and caspase-1 signal cascade in mast cells. Eur J Pharmacol 2011;671:128-32. https://doi.org/10.1016/j.ejphar.2011.09.163
  44. Moon PD, Han NR, Ryu KJ, Kang SW, Go JH, Jang JB, Choi Y, Kim HM, Jeong HJ. A novel compound 2-(4-{2-((phenylthio)acetyl)carbonohydrazonoyl}phenoxy)acetamide downregulates TSLP through blocking of caspase-1/NF-κB pathways. Int Immunopharmacol 2016;38:420-5. https://doi.org/10.1016/j.intimp.2016.06.019
  45. Kakeda M, Yamanaka K, Kitagawa H, Tsuda K, Akeda T, Kurokawa I, Gabazza EC, Mizutani H. Heat-killed bacillus Calmette-Guerin and Mycobacterium kansasii antigen 85B combined vaccination ameliorates dermatitis in a mouse model of atopic dermatitis by inducing regulatory T cells. Br J Dermatol 2012;166:953-63. https://doi.org/10.1111/j.1365-2133.2011.10763.x
  46. Kobayashi K, Inohara N, Hernandez LD, Galan JE, Nunez G, Janeway CA, Medzhitov R, Flavell RA. RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 2002;416:194-9. https://doi.org/10.1038/416194a
  47. Lamkanfi M, Kalai M, Saelens X, Declercq W, Vandenabeele P. Caspase-1 activates nuclear factor of the kappa-enhancer in B cells independently of its enzymatic activity. J Biol Chem 2004;279:24785-93. https://doi.org/10.1074/jbc.M400985200
  48. Lee HC, Ziegler SF. Inducible expression of the proallergic cytokine thymic stromal lymphopoietin in airway epithelial cells is controlled by NFkappaB. Proc Natl Acad Sci USA 2007;104:914-9. https://doi.org/10.1073/pnas.0607305104
  49. Shen D, Xie X, Zhu Z, Yu X, Liu H, Wang H, Fan H, Wang D, Jiang G, Hong M. Screening active components from Yu-ping-feng-san for regulating initiative key factors in allergic sensitization. PLoS One 2014;9:e107279. https://doi.org/10.1371/journal.pone.0107279
  50. Rizzo JM, Oyelakin A, Min S, Smalley K, Bard J, Luo W, Nyquist J, Guttman-Yassky E, Yoshida T, De Benedetto A, et al. ΔNp63 regulates IL-33 and IL-31 signaling in atopic dermatitis. Cell Death Differ 2016;23:1073-85. https://doi.org/10.1038/cdd.2015.162
  51. Choi EJ, Iwasa M, Han KI, Kim WJ, Tang Y, Hwang YJ, Chae JR, Han WC, Shin YS, Kim EK. Heat-Killed Enterococcus faecalis EF-2001 ameliorates atopic dermatitis in a murine model. Nutrients 2016;8:146. https://doi.org/10.3390/nu8030146
  52. Imaizumi A, Kawakami T, Murakami F, Soma Y, Mizoguchi M. Effective treatment of pruritus in atopic dermatitis using H1 antihistamines (secondgeneration antihistamines): changes in blood histamine and tryptase levels. J Dermatol Sci 2003;33:23-9. https://doi.org/10.1016/S0923-1811(03)00132-4

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