Effect of Daehwangmokdanpitang on psoriasis-like skin inflammation

건선 모사 피부 염증모델에서 대황목단피탕(大黃牧丹皮湯)의 효능 연구

  • Gyeong-Ran Noh (Department of Pharmacology, College of Korean Medicine, Wonkwang University) ;
  • Bitna Kweon (Department of Pharmacology, College of Korean Medicine, Wonkwang University) ;
  • Dong-Uk Kim (Department of Pharmacology, College of Korean Medicine, Wonkwang University) ;
  • Jin‑Young Oh (Department of Pharmacology, College of Korean Medicine, Wonkwang University) ;
  • Gabsik Yang (Department of Pharmacology, College of Korean Medicine, Woosuk University) ;
  • Il-Joo Jo (Central Stroke Center of Korean medicine, College of Korean Medicine, Wonkwang University)
  • 노경란 (원광대학교 한의과대학 약리학교실) ;
  • 권빛나 (원광대학교 한의과대학 약리학교실) ;
  • 김동욱 (원광대학교 한의과대학 약리학교실) ;
  • 오진영 (원광대학교 한의과대학 약리학교실) ;
  • 양갑식 (우석대학교 한의과대학 임상약리연구실) ;
  • 조일주 (원광대학교 한의과대학 뇌졸중한의중점연구센터)
  • Published : 2024.06.30

Abstract

Objectives: Psoriasis is a common chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and an excessive inflammatory response. Agents that can attenuate keratinocyte hyperproliferation and excessive inflammatory responses are considered potentially useful for the treatment of psoriasis. Daehwangmokdanpitang (DHMDPT) exhibits a broad range of bioactivities, including anti-proliferative and anti-inflammatory effects. This study aims to evaluate the anti-psoriatic potential of DHMDPT in vitro. Methods: HaCaT keratinocytes were stimulated with a mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish an in vitro psoriatic keratinocyte model. Cell viability was measured using the MTT assay. Quantitative real-time PCR (qRT-PCR) was performed to measure the mRNA levels of the hyperproliferative marker gene keratin 6 (KRT6) and inflammatory factors such as IL-6, TNF-α, and IL-23A. Additionally, chemokines including CCL5, CCL2, CCL20, and CXCL1 were measured by qRT-PCR. Results: DHMDPT attenuated M5-induced hyperproliferation, as indicated by a reduction in KRT6 expression in HaCaT keratinocytes. M5 stimulation significantly upregulated the mRNA levels of IL-6, TNF-α, and IL-23A. However, DHMDPT treatment attenuated the upregulation of IL-6 but not TNF-α or IL-23A. Additionally, DHMDPT inhibited the expression of CCL5, CCL2, and CXCL1, but not CCL20. Conclusion: DHMDPT effectively attenuated the M5-induced proliferation and inflammatory response in HaCaT keratinocytes. Therefore, DHMDPT could be an attractive candidate for future development as an anti-psoriatic agent.

Keywords

Acknowledgement

본 연구는 과학기술정보통신부의 재원으로 한국연구재단의 이공학학술연구기반구축(R&D) 지역대학 우수과학자 지원사업(RS-2023-00248541)과 보건복지부의 재원으로 한국보건산업진흥원의 보건의료 기술연구개발사업 지원(HF22C0072)에 의하여 이루어짐.

References

  1. Kim DY. Anti-inflammatory Effect of Artemisiae Capillaris Herba Extracts in Psoriasis-induced Keratinocytes. Official Journal of Korean Society for Investigative Cometology. 2023;19(4):305-11. 
  2. Xiong H, Xu Y, Tan G, Han Y, Tang Z, Xu W, Zeng F & Guo Q. Glycyrrhizin Ameliorates Imiquimod-Induced Psoriasis-like Skin Lesions in BALB/c Mice and Inhibits TNF-a-Induced ICAM-1 Expression via NF-κB/MAPK in HaCaT Cells. Cell Physiol Biochem. 2015;35(4):1335-46. 
  3. Tse WP, Che CT, Liu K, Lin ZX. Evaluation of the anti-proliferative properties of selected psoriasis-treating Chinese medicines on cultured HaCaT cells. Journal of Ethnopharmacology. 2006;108(1):133-41. 
  4. Kim MY, Hwang H. Improving effect of psoriasis dermatitis by yakuchinone A in the TNF-α stimulated HaCaT cells. Journal of Applied Biological Chemistry. 2020;63(1):95-101. 
  5. Li C, Xiao L, Jia J, Li F, Wang X, Duan Q, Jing H, Yang P, Chen C, Wang Q. Cornulin is induced in psoriasis lesions and promotes keratinocyte proliferationvia phosphoinositide 3-Kinase/Akt pathways. Journal of Investigative Dermatology. 2019;139:71-80. 
  6. Chen C, Wu N, Duan Q, Yang H, Wang X, Yang P, Zhang M, Liu J, Liu Z, Shao Y. C10orf99 contributes to the development of psoriasis by promoting the proliferation of keratinocytes. Scientifc Reports. 2018;8(1):8590. 
  7. Kook Yb, Kim SC , Park SD, Park SK, Seo BI, Seo YB, Shin SS, Lee SI, Lee JC, Lee TH, Jung JG, Joo YS, Choi HY. Herbal Formula. seoul:Yeongnimsa. 1999:609-10. 
  8. Kweon BN, Kim DU, Yang GB, Jo IJ. Prediction the efficacy and mechanism of action of Daehwangmokdanpitang to treat psoriasis based on network pharmacology. The Korea Jounrnal of Herbology. 2023;38(6):73-91. 
  9. Nguyen, LTH, Ahn SH, Shin HM, Yang IJ. Anti-Psoriatic Effect of Rheum palmatum L. and Its Underlying Molecular Mechanisms. International Journal of Molecular Sciences. 2022;23(4):16000. 
  10. Kim HY, Seol IC, Yoo HR, Kim YS. The Effect of Trichosanthes Kirilowii Maximowicz Extract and Trichosanthes Kirilowii Maximowicz Cheonghyeol Plus on Anti-Inflammatory Factor Expression inHuman Umbilical Vein Endothelial Cells (HUVECs). The Journal of Internal Korean Medicine. 2022; 43(4):514-28. 
  11. Park JH, Kim KJ. The Effect of Moutan Cortex on Pro-inflammatory Cytokines through NF-κB & MAPKs pathway in HMC-l. The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology. 2009;22(2):1-18. 
  12. Joe WA, Jang MJ, Cheon SJ, Sung JY, Choi EY, Kang BY, Jung SH, Jung YS, Kim YS, An BJ, Lee CA, Lee JT. Cosmeceutical activities and Antiinflammatoryeffects of Shell from Persicae semen. The Korea Journal of Herbology. 2006;21(2):87-93. 
  13. Guilloteau K, Paris I, Pedretti N, Boniface K, Juchaux F, Huguier V, Guillet G, Bernard F-X, Lecron J-C, Morel F. Skin infammation induced by the synergistic action of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α recapitulates some features of psoriasis. The Journal of Immunology. 2010;184:5263-70. 
  14. Greb JE, Goldminz AM, Elder JT, Lebwohl MG, Gladman DD, Wu JJ, Mehta NN, Finlay AY, Gottlieb AB. Psoriasis. Nature Review Disease Primers. 2016;2:16082. 
  15. Raj D, Brash DE, Grossman D. Keratinocyte apoptosis in epidermal development and disease. Journal of Investigative Dermatology. 2006;126(2):243-57. 
  16. Zhang X, Yin M, Zhang LJ. Keratin 6, 16 and 17-critical barrier alarmin molecules in skin wounds and psoriasis. Cells. 2019;8(8):807. 
  17. Albanesi C, Scarponi C, Giustizieri ML, Girolomoni G. Keratinocytes in infammatory skin diseases. Current Drug Targets-Infammation&Allergy. 2005;4:329-34. 
  18. Cesare AD, Meglio PD, Nestle FO. The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol. 2009;129(6):1339-50. 
  19. Fitch E, Harper E, Skorcheva I, Kurtz SE, Blauvelt A. Pathophysiology of Psoriasis:Recent Advances on IL-23 and Th17 Cytokines. Current rheumatology reports. 2007:9(6):461-67. 
  20. Grossman RM, Krueger J, Yourish D, Granelli-Piperno A, Murphy DP, May LT, Kupper TS, Sehgal PB, Gottlieb AB. Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes. Proceedings of the National Academy of Sciences. 1989;86(16):6367-71. 
  21. Neuner P, Urbanski A, Trautinger F, Moller A, Kirnbauer R, Kapp A, Schopf E, Schwarz T, Luger TA. Increased IL-6 production by monocytes and keratinocytes in patients with psoriasis. Journal of Investigative Dermatology. 1991;97(1):27-33. 
  22. Purzycka-Bohdan D, Nedoszytko B, Zablotna M, Glen J, Szczerkowska-Dobosz A, Nowicki RJ. Chemokine profile in psoriasis patients in correlation with disease severity and pruritus. International Journal of Molecular Sciences. 2022;23(21):13330. 
  23. Singh TP, Lee CH, Farber JM. Chemokine receptors in psoriasis. Expert opinion on therapeutic targets. 2013;17(12):1405-1422. 
  24. Li Q, Laumonnier Y, Syrovets T, Simmet T. Recruitment of CCR6-expressing Th17 cells by CCL20 secreted from plasmin-stimulated macrophages. Acta Biochim Biophys Sin. 2013;45(7):593-600 
  25. Novoszel P, Holcmann M, Stulnig G, De Sa Fernandes C, Zyulina V, Borek I, Linder M, Bogusch A, Drobits B, Bauer T, Tam-Amersdorfer C, Brunner PM, Stary G, Bakiri L, Wagner EF, Herbert Strobl, Sibilia M. Psoriatic skin inflammation is promoted by c-Jun/AP-1-dependent CCL2 and IL-23 expression in dendritic cells. Journal of Dermatological Science. 2021;13(4):e12409. 
  26. Sieminska I, Pieniawska M, Grzywa TM. The Immunology of Psoriasis-Current Concepts in Pathogenesis. Clinical Reviews in Allergy & Immunology. 2024:1-28. 
  27. Zdanowska N, Kasprowicz-Furmanczyk M, Placek W, Owczarczyk-Saczonek A. The Role of Chemokines in Psoriasis-An Overview. medicina. 2021;57(8):754. 
  28. Li Q, Laumonnier Y, Syrovets T, Simmet T. Recruitment of CCR6-expressing Th17 cells by CCL20 secreted from plasmin-stimulated macrophages. 2013;45(7):593-600.