Journal of Food and Nutrition Research
ISSN (Print): 2333-1119 ISSN (Online): 2333-1240 Website: http://www.sciepub.com/journal/jfnr Editor-in-chief: Prabhat Kumar Mandal
Open Access
Journal Browser
Go
Journal of Food and Nutrition Research. 2022, 10(6), 415-424
DOI: 10.12691/jfnr-10-6-5
Open AccessArticle

Orostachys japonicus Suppresses IFN-γ and TNF-α Induced Proinflammatory Chemokines in Atopic Dermatitis Relating HaCaT Cells via Down-regulation of Expression and Translocation of NF-κB

Yoo Jung Jeon1, Sung Hyun Kim2 and Dong Seok Lee1, 3,

1Institute of Digital Anti-aging Healthcare, Graduate School, Inje University, Gimhae 50834, Republic of Korea

2Department of Smart Foods and Drugs, Graduate School, Inje University, Gimhae 50834, Republic of Korea

3Department of Smart Foods and Drugs, Graduate School, Inje University, Gimhae 50834, Republic of Korea;Department of Biomedical Laboratory Science, Inje University, 197 Inje-ro, Gimhae 50834, Gyeongsangnam-do, Republic of Korea

Pub. Date: June 21, 2022

Cite this paper:
Yoo Jung Jeon, Sung Hyun Kim and Dong Seok Lee. Orostachys japonicus Suppresses IFN-γ and TNF-α Induced Proinflammatory Chemokines in Atopic Dermatitis Relating HaCaT Cells via Down-regulation of Expression and Translocation of NF-κB. Journal of Food and Nutrition Research. 2022; 10(6):415-424. doi: 10.12691/jfnr-10-6-5

Abstract

To investigate the anti-atopic dermatitis (AD) activity of dichloromethane (DCM) fraction of ethanol extracts from Orostachys japonicus (OJ) in AD relating human keratinocytes (HaCaT cells) through down-regulation of a key transcription factor NF-κB involved in skin inflammatory responses. The DCM fraction was obtained from OJ ethanol extracts and used for this study. For anti-AD activity, HaCaT cells that have been induced with IFN-γ and TNF-α at the same concentration to produce proinflammatory chemokines were used. As analysis methods, WST assay, chemokines measurement, antibody array, nuclear/cytoplasmic protein separation, and western blotting were used. WST assay showed no toxicity to cell viability. The production levels of chemokines such as MDC, RANTES, IL-8, and TARC decreased in a concentration-dependent manner. Immunoassay through the antibody array showed that the DCM fraction down-regulated the NF-κB (p65) expression. In addition, as a result of western blotting, it was revealed that the translocation of NF-κB (p65) from the cytoplasm into the nucleus decreased. The DCM fraction from OJ ethanol extracts showed significant anti-AD activity through suppression of proinflammatory chemokines causing AD in HaCaT cells via down-regulation of expression and translocation of NF-κB (p65) into the nucleus.

Keywords:
Orostachys japonicas atopic dermatitis keratinocyte chemokine HaCaT NF-κB (p65)

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Figures

Figure of 9

References:

[1]  Ngo, H.T., Fang, M., Hwang, E., Kim, YS., Park B, Seo SA, Do N.Q., Nguyen Q.T. and Yi T.H., “Inhibitory Effects of Urtica thunbergiana Ethanol Extract on Atopic Dermatitis-Induced NC/Nga Mice,” Antioxidant, 9 (3). 197-212. Mar.2020.
 
[2]  Yoo, O.K., Choi, W.J. and Keum, Y.S., “Cardamonin Inhibits Oxazolone-Induced Atopic Dermatitis by the Induction of NRF2 and the Inhibition of Th2 Cytokine Production,” Antioxidants, 9 (9). 834-845. Sep.2020.
 
[3]  Kawahara, T., Tsutsui, K., Nakanishi, E. and Inoue, T., “Hamauzu Y. Effect of the topical application of an ethanol extract of quince seeds on the development of atopic dermatitis-like symptoms in NC/Nga mice,” BMC, 17. 80-87. Jan.2017.
 
[4]  Sung, Y.Y. and Kim, H.K., “Crocin Ameliorates Atopic Dermatitis Symptoms by down Regulation of Th2 Response via Blocking of NF-κB/STAT6 Signaling Pathways in Mice,” Nutrients, 10 (11). 1625-1634. Nov.2018.
 
[5]  Lee, J.H., Lim, J.Y., Jo, E.H., Noh, H.M., Park, S., Park, M.C. and Kim, D.K., “Chijabyukpi-Tang Inhibits Pro-Inflammatory Cytokines and Chemokines via the Nrf2/HO-1 Signaling Pathway in TNF-α/IFN-γ-Stimulated HaCaT Cells and Ameliorates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions in Mice,” Frontiers in Pharmacology, 11. 1018-1028. Jul.2020.
 
[6]  Choi, Y.A., Yu, J.H., Jung, H.D., Lee, S.Y., Park, P.H., Lee, H.S., Kwon, T.K., Shin, T.Y., Lee, S.W., Rho, M.C., Jang, Y.H. and Kim, S.H., “Inhibitory effect of ethanol extract of Ampelopsis brevipedunculata rhizomes on atopic dermatitis-like skin inflammation,” Journal of Ethnopharmacology, 238. 111850-111859. Jun.2019.
 
[7]  Abdullah, A.A., Morris, K., Lwaleed, B.A., Lau, L., Jones, K., Cooper, R. and Jenkins, R., “Honey is potentially effective in the treatment of atopic dermatitis: Clinical and mechanistic studies,” Immunity Inflammation and Disease, 5 (2). 190-199. Jun.2017.
 
[8]  Lee, Y.H., Choi, H.K., N’deh, K., Choi, Y.J., Fan, M., Kim, E.K., Chung, K.H. and An, J.H., “Inhibitory Effect of Centella asiatica Extract on DNCB-Induced Atopic Dermatitis in HaCaT Cells and BALB/c Mice,” Nutrients, 12. 411-426. Feb.2020.
 
[9]  Kim, O.K., Nam, D.E., Lee, M.H., Kwon, H.O., Park, J.J., You, Y.H., Kim, S.I., Lee, J. and Jun, W., “The Effects of Costaria costata Extracts on Atopic Dermatitis in an In Vitro Model,” J Med Food, 19 (10). 945-951. Oct.2016.
 
[10]  Bao, L., Zhang, H. and Chan, L.S., “The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis,” JAK-STAT, 2 (3). 2162-3996. Jul.2013.
 
[11]  Jeong, J.H., Ryu, D.S., Suk, D.H. and Lee, D.S., “Anti-inflammatory effects of ethanol extract from Orostachys japonicus on modulation of signal pathways in LPS-stimulated RAW 264.7 cells,” BMB Reports, 44 (6). 399-404. Jun.2011.
 
[12]  Lee, H.S., Ryu, D.S., Lee, G.S. and Lee, D.S., “Anti-inflammatory effects of dichloromethane fraction from Orostachys japonicus in RAW 264.7 cells: Suppression of NF-κB activation and MAPK signaling,” Journal of Ethnopharmacology, 140 (2). 271-276. Mar.2012.
 
[13]  Lee, H.S., Bilehale, D., Lee, G.S., Ryu, D.S., Kim, H.K., Suk, D.H. and Lee, D.S., “Anti-inflammatory effect of the hexane fraction from Orostachys japonicus in RAW 264.7 cells by suppression of NF-κB and PI3K-Akt signaling,” Journal of Functional Foods, 5 (3): 1217-1225. Jul.2013.
 
[14]  Lee, H.S., Lee, G.S., Kim, S.H., Kim, H.K., Suk, D.H. and Lee, D.S., “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 Reports, 47 (2). 98-103. Feb.2014.
 
[15]  Ryu, D.S., Lee, H.S., Lee, G.S. and Lee, D.S., “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 (5). 660-665. Feb.2012.
 
[16]  Ryu, D.S., Baek, G.O., Kim, E.Y., Kim, E.Y., Kim, K.H. and Lee, D.S., “Effects of polysaccharides derived from Orostachys japonicus on induction of cell cycle arrest and apoptotic cell death in human colon cancer cells,” BMB Reports, 43 (11). 750-755. Nov.2010.
 
[17]  Ma, C.J., Jung, W.J., Lee, K.Y., Kim, Y.C. and Sung, S.H., “Calpain inhibitory flavonoids isolated from Orostachys japonicus,” Journal of Enzyme Inhibition and Medicinal Chemistry, 24 (3). 676-679. Jun.2009.
 
[18]  Lee, J.H., Lee, S.J., Park, S.M., Kim, H.K., Jeong, W.Y., Choi, J.Y., Sung, N.J., Lee, W.S., Lim, C.S., Kim, G.S. and Shin, S.C., “Characterisation of flavonoids in Orostachys japonicus A. Berger using HPLC-MS/MS: Contribution to the overall antioxidant effect,” Food Chemistry, 124 (4). 1627-1633. Feb.2011.
 
[19]  Park, H.J., Young, H.S., Park, K.Y., Rhee, S.H., Chung, H.Y. and Choi, J.S., “Flavonoids from the Whole Plants of Orostachys japonicus,” Arch Pharm Res, 14 (2). 167-171. Jun.1991.
 
[20]  Choi, S.Y., Chung, M.J., Seo, W.D., Shin, J.H., Shon, M.Y. and Sung, N.J., “Inhibitory Effects of Orostachys japonicus Extracts on the Formation of N-Nitrosodimethylamine,” J Agric Food Chem, 54. 6075-6078. Jul.2006.
 
[21]  Lee, G.S., Lee, H.S., Kim, H.S., Suk, D.H., Ryu, D.S. and Lee, D.S., “Anti-cancer Activity of the Ethylacetate Fraction from Orostachys japonicus for Modulation of the Signaling Pathway in HepG2 Human Hepatoma Cells,” Food Sc. Biotechnol, 23 (1). 269-275. Dec.2013.
 
[22]  Lee, H.Y., Park, Y.M., Kim, J., Oh, H.G., Kim, K.S., Kang, H.J., Kim, R.R., Kim, M.J., Kim, S.H., Yang, H.J. and Oh, J., “Orostachys japonicus A. Berger Extracts Induce Immunity-Enhancing Effects on Cyclophosphamide-Treated Immunosuppressed Rats,” BioMed Research International, 2019. 1-9. Jan.2019.
 
[23]  Lee, H.S., “Orostachys japonicus extract inhibits the lipopolysaccharideinduced pro-inflammatory factors by suppression of transcription factors,” Food Science & Nutrition, 8. 1812-1817. Feb.2020.
 
[24]  Debnath, T., Lee, Y.M., Lim, J.H. and Lim, B.O., “Anti-allergic and anti-atopic dermatitis effects of Gardenia Fructus extract,” Food and Agricultural Immunology, 29 (1). 665-674. Mar.2018.
 
[25]  Choi, J.K., Jang, Y.H., Lee, S.Y., Lee, S.R., Choi, Y.A., Jin, M., Choi, J.H., Park, J.H., Park, P.H., Chio, H.K., Kwon, T.K., Khang, D.W. and Kim, S.H., “Chrysin attenuates atopic dermatitis by suppressing inflammation of keratinocytes,” Food and Chemical Toxicology, 110. 142-150. Dec.2017.
 
[26]  Cho, S.H., Kim, H.S., Lee, W.W., Han, E.J., Kim, S.Y., Fernando, I.S., Ahn, G. and Kim, K.N., “Eckol from Ecklonia cava ameliorates TNF-α/IFN-γ-induced inflammatory responses via regulating MAPKs and NF-κB signaling pathway in HaCaT cells,” International Immunopharmacology, 82. 106146-106153. Feb.2020.
 
[27]  Jeong, N.H., Yang, E.J., Jin, M., Lee, J.Y., Choi, Y.A., Park, P.H., Lee, S.R., Kim, S.U., Shin, T.Y., Kwon, T.K., Jang, Y.H., Song, K.S. and Kim, S.H., “Esculetin from Fraxinus rhynchophylla attenuates atopic skin inflammation by inhibiting the expression of inflammatory cytokines,” International Immunopharmacology, 59. 209-216. Jun.2018.
 
[28]  Dao, T.P., Song, K.H., Kim, J.Y. and Kim, Y.S., “Igalan from Inula helenium (L.) suppresses the atopic dermatitislike response in stimulated HaCaT keratinocytes via JAK/STAT3 signaling,” Infammation Research, 69. 309-319. Jan .2020.
 
[29]  Cha, K.J., Im, M.A., Gu, A., Kim, D.H., Lee, D., Lee, J.S. and Kim, I.S., “Inhibitory effect of Patrinia scabiosifolia Link on the development of atopic dermatitis-like lesions in human keratinocytes and NC/Nga mice,” Journal of Ethnopharmacology, 206 (12). 135-143. Mar.2017.
 
[30]  Choi, Y.A., Yu, J.H., Jung, H.D., Lee, S.Y., Park, P.H., Lee, H.S., Kwon, T.K., Shin, T.Y., Lee, S.W., Rho, M.C., Jang, Y.H. and Kim, S.H., “Inhibitory effect of ethanol extract of Ampelopsis brevipedunculata rhizomes on atopic dermatitis-like skin inflammation,” Journal of Ethnopharmacology, 238 (28). 1-9. Apr.2019.
 
[31]  Choi, J.H., Jin, S.W., Lee, G.H., Cho, S.M. and Jeong, H.G., “Orostachys japonicus ethanol extract inhibits 2,4dinitrochlorobenzeneinduced atopic dermatitislike skin lesions in NC/Nga mice and TNFα/IFNγinduced TARC expression in HaCaT cells,” Toxicological Research, 36. 99-108. Apr.2020.
 
[32]  Ha, Y.N., Lee, Y.H., Jeong, J.W., Park, M., Ko, J.Y., Kwon, O.W., Lee, J. and Kim, Y.J., “Pyropia yezoensis Extract Suppresses IFN-Gammaand TNF-Alpha-Induced Proinflammatory Chemokine Production in HaCaT Cells via the Down-Regulation of NF-κB,” Nutrients, 12. 1238-1253. Apr.2020.
 
[33]  Hou, D.D., Di, Z.H., Qi, R.Q., Wang, H.X., Zheng, S., Hong, Y.X., Guo, H., Chen, H.D. and Gao, X.H., “Sea Buckthorn (Hippophaë rhamnoides L.) Oil Improves Atopic Dermatitis-Like Skin Lesions via Inhibition of NF-κB and STAT1 Activation,” Skin Pharmacol Physiol, 30. 268-276. Sep.2017.
 
[34]  Jin, S.E., Ha, H.K., Shin, H.K. and Seo, C.S., “Anti-Allergic and Anti-Inflammatory Effects of Kuwanon G and Morusin on MC/9 Mast Cells and HaCaT Keratinocytes,” Molecules, 24. 265-278. Jan.2019.
 
[35]  Yang, J.H., Hwang, Y.H., Gu, M.J., Cho, W.K. and Ma, J.Y., “Ethanol extracts of Sanguisorba officinalis L. suppress TNF-α/IFN-γ-induced pro-inflammatory chemokine production in HaCaT cells,” Phytomedicine, 22 (14). 1262-1268. Nov.2015.
 
[36]  Yang, J.H., Yoo, J.M., Lee, E., Lee, B.H., Cho, W.K., Park, K.I. and Ma, J.Y., “Anti-inflammatory effects of Perillae Herba ethanolic extract against TNF-α/IFN-γ-stimulated human keratinocyte HaCaT cells,” Journal of Ethnopharmacology, 211 (30). 217-223. Nov.2018.
 
[37]  Yang, J.H., Lee, E., Lee, B.H., Cho, W.K., Ma, J. and Park, K.I., “Ethanolic Extracts of Artemisia apiacea Hance Improved Atopic Dermatitis-Like Skin Lesions In Vivo and Suppressed TNF-Alpha/IFN-Gamma-Induced Proinflammatory Chemokine Production In Vitro,” Nutrients, 10. 806-816. Jul.2018.
 
[38]  Yang, J.H., Do, H.J., Lee, E., Yim, N.H., Cho, W.K., Park, K.I. and Ma, J.Y., “Jageum-Jung improves 2,4-dinitrochlorobenzene-induced atopic dermatitislike skin lesions in mice and suppresses pro-inflammatory chemokine production by inhibiting TNF-α/IFN-γ-induced STAT-1 and NFκB signaling in HaCaT cells,” Journal of Ethnopharmacology, 221 (15). 48-55. Apr.2018.
 
[39]  Cha, K.J., Kashif, A., Hong, M.H., Kim, G., Lee, J.S., Kim, I.S., “Poncirus Trifoliata (L.) Raf. Extract Inhibits the Development of Atopic Dermatitis-like Lesions in Human Keratinocytes and NC/Nga mice,” International Journal of Medical Sciences, 16 (8). 1116-1122. Aug.2019.
 
[40]  Segawa, R., Shigeeda, K., Hatayama, T., Dong, J., Mizuno, N., Moriya, T., Hiratsuka, M. and Hirasawa, N., “EGFR transactivation is involved in TNF-α-induced expression of thymic stromal lymphopoietin in human keratinocyte cell line,” Journal of Dermatological Science, 89. 290-298. Mar.2018.
 
[41]  Wu, S., Yu, D., Liu, W., Zhang, J., Liu, X., Wang, J., Yu, M., Li, Z., Chen, Q., Li, X. and Ye, X., “Magnoflorine from Coptis chinese has the potential to treat DNCB-induced Atopic dermatits by inhibiting apoptosis of keratinocyte,” Bioorganic & Medicinal Chemistry, 28 (2). 115093-115107. Sep.2020.
 
[42]  Cho, K.H., Parveen, A., Kang, M.C., Subedi, L., Lee, J.H., Park, S.Y., Jin, M.R., Yoon, H.K., Son, Y.K. and Kim, S.Y., “Pyrus ussuriensis Maxim. leaves extract ameliorates DNCB-induced atopic dermatitis-like symptoms in NC/Nga mice,” Phytomedicine, 48 (15). 76-83. May.2018.
 
[43]  Cho, K.H., Kang, M.C., Parveen, A., Yumnam, S. and Kim, S., “Anti-Inflammatory Effect of Chloroform Fraction of Pyrus ussuriensis Maxim. Leaf Extract on 2, 4-Dinitrochlorobenzene-Induced Atopic Dermatitis in nc/nga Mice,” Nutrients, 11. 276-287. Jan.2019.
 
[44]  Park, S.H., An, J.E., Jang, S., Kim, J.Y., Lee, J.W. and Kim, H.K., “Gardenia jasminoides extract without crocin improved atopic dermatitis-like skin lesions via suppression of Th2-related cytokines in Dfe-induced NC/Nga mice,” Journal of Ethnopharmacology, 241 (15). 112015-112023. Jun.2019.
 
[45]  Yang, H.J., Kim, M.J., Kang, S.A., Moon, N.R., Kim, D.S., Lee, N.R., Kim, K.S. and Park, S., “Topical treatments of Saussurea costus root and Thuja orientalis L. synergistically alleviate atopic dermatitis-like skin lesions by inhibiting protease-activated receptor-2 and NF-κB signaling in HaCaT cells and Nc/Nga mice,” Journal of Ethnopharmacology, 199 (6). 97-105. Feb.2017.
 
[46]  Hou, D.D., Zhang, W., Gao, Y.L., Sun, Y.Z., Wang, H.X., Qi, R.Q., Chen, H.D. and Gao, X.H., “Anti-inflammatory effects of quercetin in a mouse model of MC903-induced atopic dermatitis,” International Immunopharmacology, 74. 105676-105686. Jun.2019.
 
[47]  Gil, T.Y., Kang, Y.M., Eom, Y.J., Hong, C.H. and An, H.J., “Anti-Atopic Dermatitis Effect of Seaweed Fulvescens Extract via Inhibiting the STAT1 Pathway,” Mediators of Inflammation, 2019. 11-21. Mar.2019.