본문 바로가기
KERD
논문KCI 등재

Isoegomaketone Ameliorates Atopic Dermatitis via MAPK and STAT Pathway-based Pro-Inflammatory Cytokine Regulation

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

Isoegomaketone (IK), isolated from the radiation-induced mutant cultivar of Perilla frutescensvar. crispa, is a major phytochemical compound that has attracted attention in pharmacological research. In this study, we demonstrated that IK exerts anti-inflammatory and protective effects on human mastcells and in an atopic dermatitis mouse model. IK inhibited tumor necrosis factor-α (TNF-α), interleukin-6(IL-6), and IL-8 expression in human mast cells (HMC-1) stimulated with phorbol myristate acetate (PMA)and calcium ionophore A23187 (PMACI). IK significantly reduced the PMACI-induced phosphorylation ofERK and JNK, but not p38. IK also inhibited the PMACI-induced phosphorylation of STAT1 and STAT3. Oral administration of IK in atopic dermatitis mouse model ameliorated skin inflammation severity, asmeasured by skin thickness and pro-inflammatory cytokine levels such as TNF-α, IL-8, IL-4, and IL-13. These results might suggest that IK is a potent therapeutic agent against skin inflammation and atopicdermatitis.

Abstract

Isoegomaketone (IK), isolated from the radiation-induced mutant cultivar of Perilla frutescensvar. crispa, is a major phytochemical compound that has attracted attention in pharmacological research. In this study, we demonstrated that IK exerts anti-inflammatory and protective effects on human mastcells and in an atopic dermatitis mouse model. IK inhibited tumor necrosis factor-α (TNF-α), interleukin-6(IL-6), and IL-8 expression in human mast cells (HMC-1) stimulated with phorbol myristate acetate (PMA)and calcium ionophore A23187 (PMACI). IK significantly reduced the PMACI-induced phosphorylation ofERK and JNK, but not p38. IK also inhibited the PMACI-induced phosphorylation of STAT1 and STAT3. Oral administration of IK in atopic dermatitis mouse model ameliorated skin inflammation severity, asmeasured by skin thickness and pro-inflammatory cytokine levels such as TNF-α, IL-8, IL-4, and IL-13. These results might suggest that IK is a potent therapeutic agent against skin inflammation and atopicdermatitis.

참고문헌 (52)

  1. Dhyani A, "A Review on Nutritional Value, Functional Properties and Pharmacological Application of Perilla(Perilla Frutescens L)", Biomed. Pharmacol. J, 12(2), pp.649~660 (2019)[DOI]
  2. Ahmed HM, "Ethnomedicinal, phytochemical and pharmacological investigation of Perilla frutescens(L)", Britt. Molecules, 24(1), pp.102~ (2019)[DOI]
  3. Igarashi M, "A review on bioactivities of perilla : progress in research on the functions of perilla as medicine and food", Evid. Based Complement. Alternat. Med, 2013, pp.925342~ (2013)[DOI]
  4. 강시용, "한국 돌연변이육종 연구의 역사와 주요 성과 및 전망", 한국육종학회지, 52, pp.49~57 (2020), 한국육종학회[DOI]
  5. Bomi Nam, "Preparative Separation of Three Monoterpenes from<i> Perilla frutescens<", i> var.<i> crispa<, International Journal of Analytical Chemistry, pp.2019, 2019[DOI]
  6. Chang Hyun Jin, "Isoegomaketone Inhibits Lipopolysaccharide-Induced Nitric Oxide Production in RAW 264.7 Macrophages through the Heme Oxygenase-1 Induction and Inhibition of the Interferon-β-STAT-1 Pathway", Journal of Agricultural and Food Chemistry, 58(2), pp.860~867 (2010), American Chemical Society (ACS)[DOI]
  7. Cho BO, "Isoegomaketone induces apoptosis through caspase-dependent and caspase-independent pathways in human DLD1 cells", Biosci. Biotechnol. Biochem, 75(7), pp.1306~1311 (2011)[DOI]
  8. Kwon SJ, "Isoegomaketone induces apoptosis in SK-MEL-2 human melanoma cells through mitochondrial apoptotic pathway via activating the PI3K", Akt pathway, 2014, pp.45(5), 1969~1976
  9. Soon-Jae Kwon, "Induction of apoptosis by isoegomaketone from Perilla frutescens L. in B16 melanoma cells is mediated through ROS generation and mitochondrial-dependent, -independent pathway", Food and Chemical Toxicology, 65, pp.97~104 (2014), Elsevier BV[DOI]
  10. 진창현, "Isoegomaketone Upregulates Heme Oxygenase-1 in RAW264.7 Cells via ROS", p38 MAPK, Biomolecules & Therapeutics, pp.2016, 24(5)[DOI]
  11. 소양강, "들깨 잎 추출물에서 분리한 Isoegomaketone(IK)의 항 비만 효능", 생약학회지, 46(4), pp.283~288 (2015), 한국생약학회
  12. Kim YR, "Isoegomaketone from Perilla frutescens (L.) Britt stimulates MAPK", ERK pathway in human keratinocyte to promote skin wound healing, 2021, 6642606~
  13. Chang Jin, "Isoegomaketone Alleviates the Development of Collagen Antibody-Induced Arthritis in Male Balb", c Mice, 2017, pp.22(7), 1209~[DOI]
  14. Kim YR, "Isoegomaketone from the Perilla frutescens ameliorates dextran sodium sulfate-induced ulcerative colitis in mice", Nat. Prod. Commun, 17(6), pp.1~6 (2022)[DOI]
  15. Simon Francis Thomsen, "Atopic Dermatitis: Natural History, Diagnosis, and Treatment", ISRN Allergy, 2014, pp.1~7 (2014), Hindawi Limited[DOI]
  16. Bonamonte D, "The role of the environmental risk factors in the pathogenesis and clinical outcome of atopic dermatitis", Biomed. Res. Int, 2019, pp.2450605~ (2019)[DOI]
  17. Bin L, "Genetic and epigenetic studies of atopic dermatitis", Allergy Astham Clin. Immunol, 12, pp.52~ (2016)[DOI]
  18. McGirt LY, "Innate immune defects in atopic dermatitis", J. Allergy Clin. Immunol, 118(1), pp.202~208 (2006)[DOI]
  19. Shah PP, "Effect of oleic acid modified polymeric bilayered nanoparticles on percutaneous delivery of spantide II and ketoprofen", J. Control Release, 158(2), pp.336~345 (2012)[DOI]
  20. Del RJ, "Corticosteroids : options in the era of steroid-sparing therapy", J. Am. Acad. Dermatol, 53, pp.S50~S58 (2005)[DOI]
  21. 손은화, "Effects of Korean Red Ginseng Extract for the Treatment of Atopic Dermatitis-Like Skin Lesions in Mice", Journal of Ginseng Research, 35(4), pp.479~486 (2011), 고려인삼학회
  22. Park KD, "The pathogenetic effect of natural and bacterial toxins on atopic dermatitis", Toxins, 9(1), pp.3~ (2016)[DOI]
  23. Takafumi Numata, "Roles of Mast Cells in Cutaneous Diseases", Frontiers in Immunology, 13 (2022), Frontiers Media SA[DOI]
  24. Galli SJ, "IgE and mast cells in allergic disease", Nat. Med, 18(5), pp.693~704 (2012)[DOI]
  25. T. E. Damsgaard, "Mast cells and atopic dermatitis. Stereological quantification of mast cells in atopic dermatitis and normal human skin", Archives of Dermatological Research, 289(5), pp.256~260 (1997), Springer Science and Business Media LLC[DOI]
  26. Yu R, "Basophils and mast cells are crucial for reactions due to epicutaneous sensitization to ovalbumin", Exp. Dermatol, 26(9), pp.778~784 (2017)[DOI]
  27. Luo X, "Dendritic cell immunoreceptor drives atopic dermatitis by modulating oxidized CaMKII-involved mast cell activation", JCI Insight, 7(5), pp.e152559~ (2022)[DOI]
  28. Simpson EL, "Two phase 3 trials of dupilumab versus placebo in atopic dermatitis", N. Engl. J. Med, 375(24), pp.2335~2348 (2016)[DOI]
  29. Seif F, "The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells", Cell Commun. Signal, 15, pp.23~ (2017)[DOI]
  30. Zhang W, "MAPK signal pathway in the regulation of cell proliferation in mammalian cell", Cell Res, 12(1), pp.9~18 (2002)[DOI]
  31. Huang WC, "Topical Spilanthol inhibits MAPK signaling and ameliorates allergic inflammation in DNCB-induced atopic dermatitis in mice", Int. J. Mol. Sci, 20(10), pp.2490~ (2019)[DOI]
  32. Lei Bao, "The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis", JAK-STAT, 2(3), pp.e24137~ (2013), Informa UK Limited[DOI]
  33. Kasraie S, "Role of macrophages in the pathogenesis of atopic dermatitis", Mediators Inflamm, 2013, pp.942375~ (2013)[DOI]
  34. Kawakami T, "Mast cells in atopic dermatitis", Curr. Opin. Immunol, 21(6), pp.666~678 (2009)[DOI]
  35. Klonowska J, "New cytokines in the pathogenesis of atopic dermatitis-New therapeutic target", Int. J. Mol. Sci, 19(10), pp.3086~ (2018)[DOI]
  36. Kim DH, "Genistein inhibits pro-inflammatory cytokines in human mast cell activation through the inhibition of the ERK pathway", Int. J. Mol. Med, 34(6), pp.1669~1674 (2014)[DOI]
  37. Haoli Jin, "Animal Models of Atopic Dermatitis", Journal of Investigative Dermatology, 129(1), pp.31~40 (2009), Elsevier BV[DOI]
  38. Brandt EB, "Th2 cytokines and atopic dermatitis", J. Clin. Cell. Immunol, 2(3), pp.110~ (2011)[DOI]
  39. Yamanaka KI, "The role of cytokines", chemokines in the pathogenesis of atopic dermatitis, 2011, pp.41, 80~92
  40. Silverberg JI, "Atopic dermatitis in the pediatric population : A cross-sectional, international epidermilogic study", Ann. Allergy Asthma Immunol, 126(4), pp.417~428 (2021)[DOI]
  41. Barbarot S, "Epidermiology of atopic dermatitis in adults : Results from an international survey", Allergy, 73(6), pp.1284~1293 (2018)[DOI]
  42. Metz M, "Mast cells can enhance resistance to snake and honeybee venoms", Science, 313(5786), pp.526~530 (2006)[DOI]
  43. James B McLachlan, "Mast cell–derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection", Nature Immunology, 4(12), pp.1199~1205 (2003), Springer Science and Business Media LLC[DOI]
  44. Metzger H, "The receptor with high affinity for IgE", Immunol. Rev, 125, pp.37~48 (1992)[DOI]
  45. Sehra S, "Mast cells regulate epidermal barrier function and the development of allergic skin inflammation", J. Invest. Dermatol, 136(7), pp.1429~1437 (2016)[DOI]
  46. Leyva-Castillo JM, "Single-cell transcriptome profile of mouse skin undergoing antigen-driven allergic inflammation recapitulates finding in atopic dermatitis skin lesions", J. Allgery clin. Immunol, 150(2), pp.373~384 (2022)[DOI]
  47. Hagiyama M, "Increased expression of cell adhesion molecule 1by mast cells as a cause of enhanced nerve-mast cell interactioni in a hapten-induced mouse model of atopic dermatitis", Br. J. Dermatol, 168(4), pp.771~778 (2013)[DOI]
  48. Lee DH, "Mosla dianthera inhibits mast cell-mediated allergic reactions through the inhibition of histamine release and inflammatory cytokine production", Toxicol. Appl. Pharmacol, 216(3), pp.479~484 (2006)[DOI]
  49. Rauch I, "The regulation of inflammation by interferons and their STATs", JAKSTAT, 2(1), pp.e23820~ (2013)[DOI]
  50. Loh CY, "Signal transducer and activator of transcription(STATs)proteins in cancer and inflammation : Functions and therapeutic implication", Front. Oncol, 9, pp.48~ (2019)[DOI]
  51. Josephine E. Hopkins, "Selective Haptenation of Cellular or Extracellular Protein by Chemical Allergens:  Association with Cytokine Polarization", Chemical Research in Toxicology, 18(2), pp.375~381 (2005), American Chemical Society (ACS)[DOI]
  52. Xi Chen, "Antipruritic Effect of Ethyl Acetate Extract from <i>Fructus cnidii<", i> in Mice with 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis, 2020, pp.2020, 1~14[DOI]

관련 논문AI추천

이 간행물의 다른 논문 (26건)