DOI QR코드

DOI QR Code

Orostachys japonicus ethanol extract inhibits 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice and TNF-α/IFN-γ-induced TARC expression in HaCaT cells

  • Choi, Jae Ho (Department of Toxicology, College of Pharmacy, Chungnam National University) ;
  • Jin, Sun Woo (Department of Toxicology, College of Pharmacy, Chungnam National University) ;
  • Lee, Gi Ho (Department of Toxicology, College of Pharmacy, Chungnam National University) ;
  • Cho, Song Mi (Department of Horticulture, Chunnam Techno University) ;
  • Jeong, Hye Gwang (Department of Toxicology, College of Pharmacy, Chungnam National University)
  • Received : 2019.09.20
  • Accepted : 2019.10.09
  • Published : 2020.04.15

Abstract

The risk of atopic dermatitis (AD)-like skin lesions has increased due to the elevated levels of allergens worldwide. Natural-origin agents, which are effective and safe, show promise for the prevention and treatment of inflammatory conditions. Orostachys japonicus (OJ) A. Berger is an ingredient of traditional herbal medicines for fever, gingivitis, and cancer in Korea, China, and Japan. However, the effect of OJ on AD-like skin lesions is unknown. Therefore, we investigated the effect of OJ ethanol extract (OJEE) on AD-like skin symptoms in mice and cells. OJEE reduced the 2,4-dinitrochlorobenzene-induced AD severity, serum levels of IgE and TARC, and mRNA levels of TARC, TNF-α, and IL-4 in NC/Nga mice. Histopathological analysis showed that OJEE reduced the thickness of the epidermis/dermis and dermal infiltration of inflammatory cells in ear tissue. Furthermore, OJEE suppressed the TNF-α/IFN-γ-increased TARC mRNA level by inhibiting NF-κB and STAT1 activation in HaCaT cells. Taken together, our findings show that OJEE reduced the risk of AD-like skin symptoms by decreasing TARC expression via inhibiting NF-κB and STAT1 activation in skin keratinocytes and thus shows promise as an alternative therapy for AD-like skin lesions.

Keywords

Acknowledgement

This work was supported by research fund of Chungnam National University

References

  1. Leung DY (2000) Atopic dermatitis: new insights and opportunities for therapeutic intervention. J Allergy Clin Immunol 105:860-876 https://doi.org/10.1067/mai.2000.106484
  2. Udompataikul M, Limpa-o-vart D (2012) Comparative trial of 5% dexpanthenol in water-in-oil formulation with 1% hydrocortisone ointment in the treatment of childhood atopic dermatitis: a pilot study. J Drugs Dermatol 11:366-374
  3. Margolis JS, Abuabara K, Bilker W, Hoffstad O, Margolis DJ (2014) Persistence of mild to moderate atopic dermatitis. JAMA Dermatol 150:593-600 https://doi.org/10.1001/jamadermatol.2013.10271
  4. Liu FT, Goodarzi H, Chen HY (2011) IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol 41:298-310 https://doi.org/10.1007/s12016-011-8252-4
  5. Leung DY, Bieber T (2003) Atopic dermatitis. Lancet 361:151-160 https://doi.org/10.1016/S0140-6736(03)12193-9
  6. Hay RJ, Johns NE, Williams HC, Bolliger IW, Dellavalle RP, Margolis DJ, Marks R, Naldi L, Weinstock MA, Wulf SK, Michaud C, Murray JLC, Naghavi M (2014) The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Investig Dermatol 134:1527-1534 https://doi.org/10.1038/jid.2013.446
  7. Weidinger S, Novak N (2016) Atopic dermatitis. Lancet 387:1109-1122 https://doi.org/10.1016/S0140-6736(15)00149-X
  8. Rios JL, Bas E, Recio MC (2005) Effects of natural products on contact dermatitis. Curr Med Chem Anti-Inflamm Anti-Allergy Agents 4:65-80 https://doi.org/10.2174/1568014053005273
  9. Dawid-Pac R (2013) Medicinal plants used in treatment of inflammatory skin diseases. Postepy Dermatol Alergol 30:170-177 https://doi.org/10.5114/pdia.2013.35620
  10. Cho HD, Lee KW, Won YS, Shin DY, Seo KI (2019) Studies on the anti-angiogenic activities of wild and cultivated Orostachys japonicus extracts in human umbilical vein endothelial cells. J Food Sci 84:1764-1775 https://doi.org/10.1111/1750-3841.14675
  11. Lee KS, Kim SW, Lee HS (2018) Orostachys japonicus induce p53-dependent cell cycle arrest through the MAPK signaling pathway in OVCAR-3 human ovarian cancer cells. Food Sci Nutr 6:2395-2401 https://doi.org/10.1002/fsn3.836
  12. Lee SG, Kim JS, Lee HS, Lim YM, So JH, Hahn D, Ha YS, Nam JO (2017) Bioconverted Orostachys japonicas extracts suppress angiogenic activity of Ms-1 endothelial cells. Int J Mol Sci 18:E2615
  13. Kim YI, Park SW, Yoon YK, Lee KW, Lee JH, Woo HJ, Kim Y (2015) Orostachys japonicus inhibits the expression of MMP-2 and MMP-9 mRNA and modulates the expression of iNOS and COX-2 genes in human PMA-differentiated THP-1 cells via inhibition of NF-κB and MAPK activation. Mol Med Rep 12:657-662 https://doi.org/10.3892/mmr.2015.3460
  14. Lee WS, Yun JW, Nagappan A, Jung JH, Yi SM, Kim DH, Kim HJ, Kim G, Ryu CH, Shin SC, Hong SC, Choi YH, Jung JM (2015) Flavonoids from Orostachys japonicus A. Berger induces caspase-dependent apoptosis at least partly through activation of p38 MAPK pathway in U937 human leukemic cells. Asian Pac J Cancer Prev 16:465-469 https://doi.org/10.7314/APJCP.2015.16.2.465
  15. Ryu DS, Kim SH, Kwon JH, Lee DS (2014) Orostachys japonicus induces apoptosis and cell cycle arrest through the mitochondria-dependent apoptotic pathway in AGS human gastric cancer cells. Int J Oncol 45:459-469 https://doi.org/10.3892/ijo.2014.2404
  16. Shin DY, Lee WS, Jung JH, Hong SH, Park C, Kim HJ, Kim GY, Hwang HJ, Kim GS, Jung JM, Ryu CH, Shin SC, Hong SC, Choi YH (2013) Flavonoids from Orostachys japonicus A. Berger inhibit the invasion of LnCaP prostate carcinoma cells by inactivating Akt and modulating tight junctions. Int J Mol Sci 14:18407-18420 https://doi.org/10.3390/ijms140918407
  17. Ryu DS, Lee HS, Lee GS, Lee DS (2012) Effects of the ethylacetate extract of Orostachys japonicus on induction of apoptosis through the p53-mediated signaling pathway in human gastric cancer cells. Biol Pharm Bull 35:660-665 https://doi.org/10.1248/bpb.35.660
  18. Ryu DS, Baek GO, Kim EY, Kim KH, Lee DS (2010) Effects of polysaccharides derived from Orostachys japonicus on induction of cell cycle arrest and apoptotic cell death in human colon cancer cells. BMB Rep 43:750-755 https://doi.org/10.5483/BMBRep.2010.43.11.750
  19. Jang M, Choi HY, Kim GH (2019) Phenolic components rich ethyl acetate fraction of Orostachys japonicus inhibits lipid accumulation by regulating reactive oxygen species generation in adipogenesis. J Food Biochem 43:e12939
  20. Jeong H, Kim JW, Yang D, Jeong TW, Zhao J, Seo JH, Shin DG, Cha JD, Han KM, Lim CW, Kim B (2019) Orostachys japonicus A. Berger (Crassulaceae) exerts antidiabetic activity by improving glucose and lipid levels in Type 2 diabetic mice. J Med Food 22:797-809 https://doi.org/10.1089/jmf.2018.4391
  21. Lee SJ, Zhang GF, Sung NJ (2011) Hypolipidemic and hypoglycemic effects of Orostachys japonicus A. Berger extracts in streptozotocin-induced diabetic rats. Nutr Res Pract 5:301-307 https://doi.org/10.4162/nrp.2011.5.4.301
  22. Koppula S, Yum MJ, Kim JS, Shin GM, Chae YJ, Yoon T, Chun CS, Lee JD, Song M (2017) Anti-fibrotic effects of Orostachys japonicus A. Berger (Crassulaceae) on hepatic stellate cells and thioacetamide-induced fibrosis in rats. Nutr Res Pract 11:470-478 https://doi.org/10.4162/nrp.2017.11.6.470
  23. Kim YI, Park SW, Choi IH, Lee JH, Woo HJ, Kim Y (2011) Effect of Orostachys japonicus on cell growth and apoptosis in human hepatic stellate cell line LX2. Am J Chin Med 39:601-613 https://doi.org/10.1142/S0192415X11009068
  24. Yoon YK, Woo HJ, Kim Y (2015) Orostachys japonicus inhibits expression of the TLR4, NOD2, iNOS, and COX-2 genes in LPS-stimulated human PMA-differentiated THP-1 cells by inhibiting NF-κB and MAPK activation. Evid Based Complement Alternat Med 2015:682019
  25. Lee HS, Ryu DS, Lee GS, Lee DS (2012) Anti-inflammatory effects of dichloromethane fraction from Orostachys japonicus in RAW 264.7 cells: suppression of NF-κB activation and MAPK signaling. J Ethnopharmacol 140:271-276 https://doi.org/10.1016/j.jep.2012.01.016
  26. Jeong JH, Ryu DS, Suk DH, Lee DS (2011) Anti-inflammatory effects of ethanol extract from Orostachys japonicus on modulation of signal pathways in LPS-stimulated RAW 264.7 cells. BMB Rep 44:399-404 https://doi.org/10.5483/BMBRep.2011.44.6.399
  27. Im DS, Lee JM, Lee J, Shin HJ, No KT, Park SH, Kim K (2017) Inhibition of collagenase and melanogenesis by ethanol extracts of Orostachys japonicus A. Berger: possible involvement of Erk and Akt signaling pathways in melanoma cells. Acta Biochim Biophys Sin 49:945-953 https://doi.org/10.1093/abbs/gmx090
  28. Lee HS, Lee GS, Kim SH, Kim HK, Suk DH, Lee DS (2014) Anti-oxidizing effect of the dichloromethane and hexane fractions from Orostachys japonicus in LPS-stimulated RAW 264.7 cells via upregulation of Nrf2 expression and activation of MAPK signaling pathway. BMB Rep 47:98-103 https://doi.org/10.5483/BMBRep.2014.47.2.088
  29. Yoon Y, Kim KS, Hong SG, Kang BJ, Lee MY, Cho DW (2000) Protective effects of Orostachys japonicus A. Berger (Crassulaceae) on H2O2-induced apoptosis in GT1-1 mouse hypothalamic neuronal cell line. J Ethnopharmacol 69:73-78 https://doi.org/10.1016/S0378-8741(99)00107-5
  30. Jung HJ, Choi J, Nam JH, Park HJ (2007) Anti-ulcerogenic effects of the flavonoid-rich fraction from the extract of Orostachys japonicus in mice. J Med Food 10:702-706 https://doi.org/10.1089/jmf.2006.223
  31. Shim KS, Ha H, Kim T, Lee CJ, Ma JY (2015) Orostachys japonicus suppresses osteoclast differentiation by inhibiting NFATc1 expression. Am J Chin Med 43:1013-1030 https://doi.org/10.1142/S0192415X15500585
  32. Hur JM, Park JC (2006) Effects of the aerial parts of Orostachys japonicus and its bioactive component on hepatic alcohol-metabolizing enzyme system. J Med Food 9:336-341 https://doi.org/10.1089/jmf.2006.9.336
  33. Park JC, Han WD, Park JR, Choi SH, Choi JW (2005) Changes in hepatic drug metabolizing enzymes and lipid peroxidation by methanol extract and major compound of Orostachys japonicus. J Ethnopharmacol 102:313-318 https://doi.org/10.1016/j.jep.2005.06.023
  34. Lee HY, Park YM, Kim J, Oh HG, Kim KS, Kang HJ, Kim RR, Kim MJ, Kim SH, Yang HJ, Oh J (2019) Orostachys japonicus A. Berger extracts induce immunity-enhancing effects on cyclophosphamide-treated immunosuppressed rats. Biomed Res Int 2019:9461960 https://doi.org/10.1155/2019/9461960
  35. Park HJ, Yang HJ, Kim KH, Kim SH (2015) Aqueous extract of Orostachys japonicus A. Berger exerts immunostimulatory activity in RAW 264.7 macrophages. J Ethnopharmacol 170:210-217 https://doi.org/10.1016/j.jep.2015.04.012
  36. Choi JH, Jin SW, Park BH, Kim HG, Khanal T, Han HJ, Hwang YP, Choi JM, Chung YC, Hwang SK, Jeong TC, Jeong HG (2013) Cultivated ginseng inhibits 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice and TNF-α/IFN-γ-induced TARC activation in HaCaT cells. Food Chem Toxicol 56:195-203 https://doi.org/10.1016/j.fct.2013.02.037
  37. Fusenig NE, Boukamp P (1998) Multiple stages and genetic alterations in immortalization, malignant transformation, and tumor progression of human skin keratinocytes. Mol Carcinog 23:144-158 https://doi.org/10.1002/(SICI)1098-2744(199811)23:3<144::AID-MC3>3.0.CO;2-U
  38. Choi JH, Hwang YP, Han EH, Kim HG, Park BH, Lee HS, Park BK, Lee YC, Chung YC, Jeong HG (2011) Inhibition of acrolein-stimulated MUC5AC expression by Platycodon grandiflorum root-derived saponin in A549 cells. Food Chem Toxicol 49:2157-2166 https://doi.org/10.1016/j.fct.2011.05.030
  39. Kabashima-Kubo R, Nakamura M, Sakabe J, Sugita K, Hino R, Mori T, Kobayashi M, Bito T, Kabashima K, Ogasawara K, Nomura Y, Nomura T, Akiyama M, Shimizu H, Tokura Y (2012) A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: possible immunological state of the intrinsic type. J Dermatol Sci 67:37-43 https://doi.org/10.1016/j.jdermsci.2012.04.004
  40. Choi JH, Jin SW, Han EH, Park BH, Kim HG, Khanal T, Hwang YP, Do MT, Lee HS, Chung YC, Kim HS, Jeong TC, Jeong HG (2014) Platycodon grandiflorum root-derived saponins attenuate atopic dermatitis-like skin lesions via suppression of NF-κB and STAT1 and activation of Nrf2/ARE-mediated heme oxygenase-1. Phytomedicine 21:1053-1061 https://doi.org/10.1016/j.phymed.2014.04.011
  41. Jin H, Kumar L, Mathias C, Zurakowski D, Oettgen H, Gorelik L, Geha R (2009) Toll-like receptor 2 is important for the T(H)1 response to cutaneous sensitization. J Allergy Clin Immunol 123:875-882 https://doi.org/10.1016/j.jaci.2009.02.007
  42. Werfel T, Morita A, Grewe M, Renz H, Wahn U, Krutmann J, Kapp A (1996) Allergen specificity of skin-infiltrating T cells is not restricted to a type-2 cytokine pattern in chronic skin lesions of atopic dermatitis. J Investig Dermatol 107:871-876 https://doi.org/10.1111/1523-1747.ep12331164
  43. Tamaki K, Kakinuma T, Saeki H, Horikawa T, Kataoka Y, Fujisawa T, Sato S, Takehara K, Nakahara T, Fukagawa S, Furue M (2006) Serum levels of CCL17/TARC in various skin diseases. J Dermatol 33:300-302 https://doi.org/10.1111/j.1346-8138.2006.00072.x
  44. Han NR, Moon PD, Kim HM, Jeong HJ (2012) Effect of Pyeongwee-San (KMP6) on 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice. Life Sci 90:147-153 https://doi.org/10.1016/j.lfs.2011.10.015
  45. Jung BG, Cho SJ, Ko JH, Lee BJ (2010) Inhibitory effects of interleukin-10 plasmid DNA on the development of atopic dermatitislike skin lesions in NC/Nga mice. J Vet Sci 11:213-220 https://doi.org/10.4142/jvs.2010.11.3.213
  46. Yang G, Lee K, Lee MH, Kim SH, Ham IH, Choi HY (2011) Inhibitory effects of Chelidonium majus extract on atopic dermatitis-like skin lesions in NC/Nga mice. J Ethnopharmacol 138:398-403 https://doi.org/10.1016/j.jep.2011.09.028
  47. Yatagai T, Shimauchi T, Yamaguchi H, Sakabe JI, Aoshima M, Ikeya S, Tatsuno K, Fujiyama T, Ito T, Ojima T, Tokura Y (2018) Sensitive skin is highly frequent in extrinsic atopic dermatitis and correlates with disease severity markers but not necessarily with skin barrier impairment. J Dermatol Sci 89:33-39 https://doi.org/10.1016/j.jdermsci.2017.10.011
  48. Darnell JE Jr, Kerr IM, Stark GR (1994) Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264:1415-1421 https://doi.org/10.1126/science.8197455
  49. Yoon NY, Min BS, Lee HK, Park JC, Choi JS (2009) A potent anti-complementary acylated sterol glucoside from Orostachys japonicus. Arch Pharm Res 28:892-896 https://doi.org/10.1007/BF02973873
  50. Je Ma C, Jung WJ, Lee KY, Kim YC, Sung SH (2009) Calpain inhibitory flavonoids isolated from Orostachys japonicus. J Enzyme Inhib Med Chem 24:676-679 https://doi.org/10.1080/14756360802328075

Cited by

  1. Ex Vivo Live Full-Thickness Porcine Skin Model as a Versatile In Vitro Testing Method for Skin Barrier Research vol.22, pp.2, 2020, https://doi.org/10.3390/ijms22020657
  2. Impressic Acid Ameliorates Atopic Dermatitis-Like Skin Lesions by Inhibiting ERK1/2-Mediated Phosphorylation of NF-κB and STAT1 vol.22, pp.5, 2020, https://doi.org/10.3390/ijms22052334
  3. Topical application of celastrol alleviates atopic dermatitis symptoms mediated through the regulation of thymic stromal lymphopoietin and group 2 innate lymphoid cells vol.84, pp.22, 2021, https://doi.org/10.1080/15287394.2021.1955785
  4. Effects of chloroform fraction of Fritillariae Thunbergii Bulbus on atopic symptoms in a DNCB-induced atopic dermatitis-like skin lesion model and in vitro models. vol.281, 2021, https://doi.org/10.1016/j.jep.2021.114453