The Anti-psoriatic Effect of Gallic Acid is Associated with the Suppression
of Keratin 6 and Nrf2

Jinwei      Zhang; Hong      Qiu; Xiaojing      Cao; Ling      Han
doi:10.2174/1570180820666230314103222
Abstract

Background: Psoriasis is recognized as an autoimmune dermatosis, and keratin 6 (KRT 6) is a hallmark of psoriasis. Gallic acid (GA) is a natural and small molecule with a series of biological activities. However, the effect of GA on psoriasis has not been clarified.
Aims: This study aimed to investigate the anti-psoriatic activity of GA in psoriasis-like mice and in vitro.
Methods: The transcriptions of the Homo sapiens KRT6 gene, and Mus musculus KRT6 gene, were identified using a quantitative real-time reverse transcriptase PCR (qRT-PCR) assay. Expressions of KRT 6, STAT3, pSTAT3, Nrf2, and pNrf2 in HaCaT cells and skin biopsies were determined with a western blotting assay. The immunofluorescence (IF) assay was used to examine the expression of KRT6, pSTAT3, and pNrf2 in HaCaT cells. The expression of KRT 6, PCNA, Ki67, and CD3 was evaluated on the skin of psoriasis-like mice and quantified with histochemical scores (H scores).
Results: GA significantly inhibited KRT 6 gene transcription and expression in psoriasis-like disease both in vitro and in vivo. It significantly inhibited the expression of keratinocyte proliferation markers (PCNA and Ki67), suppressed the expression of CD3 (a marker of T cells), and decreased the thickness of the folded skin, as well as improved the splenomegaly in imiquimod-induced mice similar to psoriasis. Furthermore, the suppressing effect of GA on KRT 6 was abolished by the continuous activation of Nrf2 rather than STAT3, although GA significantly inhibited Nrf2 and STAT3 activation in IL-17A-induced HaCaT cells.
Conclusions: KRT 6 acts as a potential target for GA against psoriasis, and the anti-psoriatic effect of GA could be related to Nrf2 signaling.
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[1]
Kozłowska, D.; Myśliwiec, H.; Harasim-Symbor, E.; Milewska, A.J.; Chabowski, A.; Flisiak, I. Serum fatty acid binding protein 5 (FABP5) as a potential biomarker of inflammation in psoriasis. Mol. Biol. Rep.,  2021, 48(5), 4421-4429.
 [http://dx.doi.org/10.1007/s11033-021-06461-3] [PMID: 34131888]

[2]
Boehncke, W.H.; Schön, M.P. Psoriasis. Lancet,  2015, 386(9997), 983-994.
 [http://dx.doi.org/10.1016/S0140-6736(14)61909-7] [PMID: 26025581]

[3]
Ryan, C.; Kirby, B. Psoriasis is a systemic disease with multiple cardiovascular and metabolic comorbidities. Dermatol. Clin.,  2015, 33(1), 41-55.
 [http://dx.doi.org/10.1016/j.det.2014.09.004] [PMID: 25412782]

[4]
Nijsten, T.; Wakkee, M. Complexity of the association between psoriasis and comorbidities. J. Invest. Dermatol.,  2009, 129(7), 1601-1603.
 [http://dx.doi.org/10.1038/jid.2009.55] [PMID: 19521405]

[5]
Sommer, R.; Mrowietz, U.; Radtke, M.A.; Schäfer, I.; von Kiedrowski, R.; Strömer, K.; Enk, A.; Maul, J-T.; Reich, K.; Zander, N.; Augustin, M. What is psoriasis? - Perception and assessment of psoriasis among the German population. J. Dtsch. Dermatol. Ges.,  2018, 16(6), 703-710.
 [http://dx.doi.org/10.1111/ddg.13539]

[6]
Benhadou, F.; Glitzner, E.; Brisebarre, A.; Swedlund, B.; Song, Y.; Dubois, C.; Rozzi, M.; Paulissen, C.; del Marmol, V.; Sibilia, M.; Blanpain, C. Epidermal autonomous VEGFA/Flt1/Nrp1 functions mediate psoriasis-like disease. Sci. Adv.,  2020, 6(2), eaax5849.
 [http://dx.doi.org/10.1126/sciadv.aax5849] [PMID: 31934626]

[7]
Bovenschen, H.J.; Otero, M.E.; Langewouters, A.M.G.; van Vlijmen-Willems, I.M.J.J.; van Rens, D.W.A.; Seyger, M.M.B.; van de Kerkhof, P.C.M. Oral retinoic acid metabolism blocking agent Rambazole TM for plaque psoriasis: An immunohistochemical study. Br. J. Dermatol.,  2007, 156(2), 263-270.
 [http://dx.doi.org/10.1111/j.1365-2133.2006.07660.x] [PMID: 17223865]

[8]
Kumar, V.; Bouameur, J.E.; Bär, J.; Rice, R.H.; Hornig-Do, H.T.; Roop, D.R.; Schwarz, N.; Brodesser, S.; Thiering, S.; Leube, R.E.; Wiesner, R.J.; Vijayaraj, P.; Brazel, C.B.; Heller, S.; Binder, H.; Löffler-Wirth, H.; Seibel, P.; Magin, T.M. A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity. J. Cell Biol.,  2015, 211(5), 1057-1075.
 [http://dx.doi.org/10.1083/jcb.201404147] [PMID: 26644517]

[9]
Lee, J.; Song, K.; Hiebert, P.; Werner, S.; Kim, T.G.; Kim, Y.S. Tussilagonone ameliorates psoriatic Features in Keratinocytes and imiquimod-induced psoriasis-like lesions in mice via NRF2 activation. J. Invest. Dermatol.,  2020, 140(6), 1223-1232.e4.
 [http://dx.doi.org/10.1016/j.jid.2019.12.008] [PMID: 31877316]

[10]
Van Duijnhoven, M.; Hagenberg, R.; Pasch, M.; Van Erp, P.; Van De Kerkhof, P. Novel quantitative immunofluorescent technique reveals improvements in epidermal cell populations after mild treatment of psoriasis. Acta Derm. Venereol.,  2005, 1(1), 1.
 [http://dx.doi.org/10.1080/00015550510027757] [PMID: 16191851]

[11]
Jiang, M.; Li, B.; Zhang, J.; Hu, L.; Dang, E.; Wang, G. Vascular endothelial growth factor driving aberrant keratin expression pattern contributes to the pathogenesis of psoriasis. Exp. Cell Res.,  2017, 360(2), 310-319.
 [http://dx.doi.org/10.1016/j.yexcr.2017.09.021] [PMID: 28928080]

[12]
Besgen, P.; Trommler, P.; Vollmer, S.; Prinz, J.C. Ezrin, maspin, peroxiredoxin 2, and heat shock protein 27: Potential targets of a streptococcal-induced autoimmune response in psoriasis. J. Immunol.,  2010, 184(9), 5392-5402.
 [http://dx.doi.org/10.4049/jimmunol.0903520] [PMID: 20363977]

[13]
Song, C.; Yang, C.; Meng, S.; Li, M.; Wang, X.; Zhu, Y.; Kong, L.; Lv, W.; Qiao, H.; Sun, Y. Deciphering the mechanism of Fang-Ji-Di-Huang-Decoction in ameliorating psoriasis-like skin inflammation via the inhibition of IL-23/Th17 cell axis. J. Ethnopharmacol.,  2021, 281, 114571.
 [http://dx.doi.org/10.1016/j.jep.2021.114571] [PMID: 34464701]

[14]
Tuli, H.S.; Mistry, H.; Kaur, G.; Aggarwal, D.; Garg, V.K.; Mittal, S.; Yerer, M.B.; Sak, K.; Khan, M.A. Gallic acid: A dietary polyphenol that exhibits anti-neoplastic activities by modulating multiple oncogenic targets. Anticancer. Agents Med. Chem.,  2022, 22(3), 499-514.
 [http://dx.doi.org/10.2174/1871520621666211119085834] [PMID: 34802408]

[15]
Nguyen-Ngo, C.; Salomon, C.; Lai, A.; Willcox, J.C.; Lappas, M. Anti-inflammatory effects of gallic acid in human gestational tissues in vitro. Reproduction,  2020, 160(4), 561-578.
 [http://dx.doi.org/10.1530/REP-20-0249] [PMID: 32698152]

[16]
Ho, I.Y.M.; Abdul Aziz, A.; Mat Junit, S. Evaluation of anti-proliferative effects of barringtonia racemosa and gallic acid on Caco-2 cells. Sci. Rep.,  2020, 10(1), 9987.
 [http://dx.doi.org/10.1038/s41598-020-66913-x] [PMID: 32561807]

[17]
Kamatham, S.; Kumar, N.; Gudipalli, P. Isolation and characterization of gallic acid and methyl gallate from the seed coats of Givotia rottleriformis Griff. and their anti-proliferative effect on human epidermoid carcinoma A431 cells. Toxicol. Rep.,  2015, 2, 520-529.
 [http://dx.doi.org/10.1016/j.toxrep.2015.03.001] [PMID: 28962387]

[18]
El-Lakkany, N.M.; El-Maadawy, W.H.; Seif el-Din, S.H.; Saleh, S.; Safar, M.M.; Ezzat, S.M.; Mohamed, S.H.; Botros, S.S.; Demerdash, Z.; Hammam, O.A. Antifibrotic effects of gallic acid on hepatic stellate cells: In vitro and in vivo mechanistic study. J. Tradit. Complement. Med.,  2019, 9(1), 45-53.
 [http://dx.doi.org/10.1016/j.jtcme.2018.01.010] [PMID: 30671365]

[19]
Silva, R.L.S.; Lins, T.L.B.G.; Monte, A.P.O.; de Andrade, K.O.; de Sousa Barberino, R.; da Silva, G.A.L.; Campinho, D.S.P.; Junior, R.C.P.; Matos, M.H.T. Protective effect of gallic acid on doxorubicin-induced ovarian toxicity in mouse. Reprod. Toxicol.,  2023, 115, 147-156.
 [http://dx.doi.org/10.1016/j.reprotox.2022.12.008] [PMID: 36572231]

[20]
Sun, G.L.; Wang, D. Gallic acid from Terminalia chebula inhibited the growth of esophageal carcinoma cells by suppressing the Hippo signal pathway. Iran. J. Basic Med. Sci.,  2020, 23(11), 1401-1408.
 [PMID: 33235697]

[21]
Wang, D.; Bao, B. Gallic acid impedes non-small cell lung cancer progression via suppression of EGFR-dependent CARM1-PELP1 complex. Drug Des. Devel. Ther.,  2020, 14, 1583-1592.
 [http://dx.doi.org/10.2147/DDDT.S228123] [PMID: 32425504]

[22]
Deng, B.; Yang, B.; Chen, J.; Wang, S.; Zhang, W.; Guo, Y.; Han, Y.; Li, H.; Dang, Y.; Yuan, Y.; Dai, X.; Zang, Y.; Li, Y.; Li, B. Gallic acid induces T-helper-1-like T reg cells and strengthens immune checkpoint blockade efficacy. J. Immunother. Cancer,  2022, 10(7), e004037.
 [http://dx.doi.org/10.1136/jitc-2021-004037] [PMID: 35817479]

[23]
Zhang, J.; Li, X.; Wei, J.; Chen, H.; Lu, Y.; Li, L.; Han, L.; Lu, C. Gallic acid inhibits the expression of keratin 16 and keratin 17 through Nrf2 in psoriasis-like skin disease. Int. Immunopharmacol.,  2018, 65, 84-95.
 [http://dx.doi.org/10.1016/j.intimp.2018.09.048] [PMID: 30293051]

[24]
Balkrishna, A.; Sakat, S.; Joshi, K.; Singh, R.; Verma, S.; Nain, P.; Bhattacharya, K.; Varshney, A. Modulation of psoriatic-like skin inflammation by traditional indian medicine divya-kayakalp-vati and oil through attenuation of pro-inflammatory cytokines. J. Tradit. Complement. Med.,  2022, 12(4), 335-344.
 [http://dx.doi.org/10.1016/j.jtcme.2021.09.003] [PMID: 35747349]

[25]
Li, Y.; Zong, J.; Ye, W.; Fu, Y.; Gu, X.; Pan, W.; Yang, L.; Zhang, T.; Zhou, M. Pithecellobium clypearia: Amelioration effect on imiquimod-induced psoriasis in mice based on a tissue metabonomic analysis. Front. Pharmacol.,  2021, 12, 748772.
 [http://dx.doi.org/10.3389/fphar.2021.748772] [PMID: 34603060]

[26]
Ding, Y.; Liu, L.; Wu, Y.; Wang, Y.; Zhao, R. Astilbin microemulsion transdermal delivery system optimization with enhancive stability and anti-psoriasis effect. Curr. Drug Deliv.,  2022, 20(3), 281-291.
 [http://dx.doi.org/10.2174/1567201819666220425092114] [PMID: 35469567]

[27]
Zamudio-Cuevas, Y.; Andonegui-Elguera, M.A.; Aparicio-Juárez, A.; Aguillón-Solís, E.; Martínez-Flores, K.; Ruvalcaba-Paredes, E.; Velasquillo-Martínez, C.; Ibarra, C.; Martínez-López, V.; Gutiérrez, M.; García-Arrazola, R.; Hernández-Valencia, C.G.; Romero-Montero, A.; Hernández-Valdepeña, M.A.; Gimeno, M.; Sánchez-Sánchez, R. The enzymatic poly(gallic acid) reduces pro-inflammatory cytokines in vitro, a potential application in inflammatory diseases. Inflammation,  2021, 44(1), 174-185.
 [http://dx.doi.org/10.1007/s10753-020-01319-5] [PMID: 32803665]

[28]
Zhang, X.; Yin, M.; Zhang, L. Keratin 6, 16 and 17—Critical barrier alarmin molecules in skin wounds and psoriasis. Cells,  2019, 8(8), 807.
 [http://dx.doi.org/10.3390/cells8080807] [PMID: 31374826]

[29]
Navarro, J.M.; Casatorres, J.; Jorcano, J.L. Elements controlling the expression and induction of the skin hyperproliferation-associated keratin K6. J. Biol. Chem.,  1995, 270(36), 21362-21367.
 [http://dx.doi.org/10.1074/jbc.270.36.21362] [PMID: 7545670]

[30]
Körver, J.E.M.; Van Duijnhoven, M.W.F.M.; Pasch, M.C.; Van Erp, P.E.J.; Van De Kerkhof, P.C.M. Assessment of epidermal subpopulations and proliferation in healthy skin, symptomless and lesional skin of spreading psoriasis. Br. J. Dermatol.,  2006, 155(4), 688-694.
 [http://dx.doi.org/10.1111/j.1365-2133.2006.07403.x] [PMID: 16965416]

[31]
Shen, Z.; Chen, L.; Liu, Y.F.; Gao, T.W.; Wang, G.; Fan, X.L.; Fan, J.Y.; Fan, P.S.; Li, C.Y.; Liu, B.; Dang, Y.P.; Li, C.X. Altered keratin 17 peptide ligands inhibit in vitro proliferation of keratinocytes and T cells isolated from patients with psoriasis. J. Am. Acad. Dermatol.,  2006, 54(6), 992-1002.
 [http://dx.doi.org/10.1016/j.jaad.2006.02.033] [PMID: 16713453]

[32]
Conrad, C.; Boyman, O.; Tonel, G.; Tun-Kyi, A.; Laggner, U.; de Fougerolles, A.; Kotelianski, V.; Gardner, H.; Nestle, F.O. α1β1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis. Nat. Med.,  2007, 13(7), 836-842.
 [http://dx.doi.org/10.1038/nm1605] [PMID: 17603494]

[33]
Page, K.M.; Suarez-Farinas, M.; Suprun, M.; Zhang, W.; Garcet, S.; Fuentes-Duculan, J.; Li, X.; Scaramozza, M.; Kieras, E.; Banfield, C.; Clark, J.D.; Fensome, A.; Krueger, J.G.; Peeva, E. Molecular and cellular responses to the TYK2/JAK1 inhibitor PF-06700841 reveal reduction of skin inflammation in plaque psoriasis. J. Invest. Dermatol.,  2020, 140(8), 1546-1555.e4.
 [http://dx.doi.org/10.1016/j.jid.2019.11.027] [PMID: 31972249]

[34]
Witte, K.; Jürchott, K.; Christou, D.; Hecht, J.; Salinas, G.; Krüger, U.; Klein, O.; Kokolakis, G.; Witte-Händel, E.; Mössner, R.; Volk, H.D.; Wolk, K.; Sabat, R. Increased presence and differential molecular imprinting of transit amplifying cells in psoriasis. J. Mol. Med.  ,  2020, 98(1), 111-122.
 [http://dx.doi.org/10.1007/s00109-019-01860-3] [PMID: 31832701]

[35]
Thatikonda, S.; Pooladanda, V.; Sigalapalli, D.K.; Godugu, C. Piperlongumine regulates epigenetic modulation and alleviates psoriasis-like skin inflammation via inhibition of hyperproliferation and inflammation. Cell Death Dis.,  2020, 11(1), 21.
 [http://dx.doi.org/10.1038/s41419-019-2212-y] [PMID: 31924750]

[36]
Calautti, E.; Avalle, L.; Poli, V. Psoriasis: A STAT3-Centric View. Int. J. Mol. Sci.,  2018, 19(1), 171.
 [http://dx.doi.org/10.3390/ijms19010171] [PMID: 29316631]

[37]
Heidarian, E.; Keloushadi, M.; Ghatreh-Samani, K.; Valipour, P. The reduction of IL-6 gene expression, pAKT, pERK1/2, pSTAT3 signaling pathways and invasion activity by gallic acid in prostate cancer PC3 cells. Biomed. Pharmacother.,  2016, 84, 264-269.
 [http://dx.doi.org/10.1016/j.biopha.2016.09.046] [PMID: 27665471]

[38]
Kim, S.A.; Ryu, Y.W.; Kwon, J.I.; Choe, M.S.; Jung, J.W.; Cho, J.W. Differential expression of cyclin D1, Ki 67, pRb, and p53 in psoriatic skin lesions and normal skin. Mol. Med. Rep.,  2018, 17(1), 735-742.
 [PMID: 29115643]

[39]
Lee, T.L.; Chang, M.L.; Lin, Y.J.; Tsai, M.H.; Chang, Y.H.; Chuang, C.M.; Chien, Y.; Sosinowski, T.; Wang, C.H.; Chen, Y.Y.; Lee, C.K.; Chen, J.S.; Wang, L.F.; Kung, J.T.; Ku, C.C. An alternatively spliced IL-15 isoform modulates abrasion-induced keratinocyte activation. J. Invest. Dermatol.,  2015, 135(5), 1329-1337.
 [http://dx.doi.org/10.1038/jid.2015.17] [PMID: 25615554]

[40]
Zhu, H.; Lou, F.; Yin, Q.; Gao, Y.; Sun, Y.; Bai, J.; Xu, Z.; Liu, Z.; Cai, W.; Ke, F.; Zhang, L.; Zhou, H.; Wang, H.; Wang, G.; Chen, X.; Zhang, H.; Wang, Z.; Ginhoux, F.; Lu, C.; Su, B.; Wang, H. RIG‐I antiviral signaling drives interleukin‐23 production and psoriasis‐like skin disease. EMBO Mol. Med.,  2017, 9(5), 589-604.
 [http://dx.doi.org/10.15252/emmm.201607027] [PMID: 28377495]

[41]
Tang, L.; He, S.; Wang, X.; Liu, H.; Zhu, Y.; Feng, B.; Su, Z.; Zhu, W.; Liu, B.; Xu, F.; Li, C.; Zhao, J.; Zheng, X.; Lu, C.; Zheng, G. Cryptotanshinone reduces psoriatic epidermal hyperplasia via inhibiting the activation of STAT3. Exp. Dermatol.,  2018, 27(3), 268-275.
 [http://dx.doi.org/10.1111/exd.13511] [PMID: 29427477]

[42]
Zhang, S.; Liu, X.; Mei, L.; Wang, H.; Fang, F. Epigallocatechin-3-gallate (EGCG) inhibits imiquimod-induced psoriasis-like inflammation of BALB/c mice. BMC Complement. Altern. Med.,  2016, 16(1), 334.
 [http://dx.doi.org/10.1186/s12906-016-1325-4] [PMID: 27581210]

[43]
Boyman, O.; Hefti, H.P.; Conrad, C.; Nickoloff, B.J.; Suter, M.; Nestle, F.O. Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-alpha. J. Exp. Med.,  2004, 199(5), 731-736.
 [http://dx.doi.org/10.1084/jem.20031482] [PMID: 14981113]

[44]
Shams, K.; Wilson, G.J.; Singh, M.; van den Bogaard, E.H.; Le Brocq, M.L.; Holmes, S.; Schalkwijk, J.; Burden, A.D.; McKimmie, C.S.; Graham, G.J. Spread of psoriasiform inflammation to remote tissues is restricted by the atypical chemokine receptor ACKR2. J. Invest. Dermatol.,  2017, 137(1), 85-94.
 [http://dx.doi.org/10.1016/j.jid.2016.07.039] [PMID: 27568525]

[45]
Levy, D.E.; Darnell, J.E. Jr STATs: Transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol.,  2002, 3(9), 651-662.
 [http://dx.doi.org/10.1038/nrm909] [PMID: 12209125]

[46]
Platanitis, E.; Decker, T. Regulatory networks involving STATs, IRFs, and NFκB in inflammation. Front. Immunol.,  2018, 9, 2542.
 [http://dx.doi.org/10.3389/fimmu.2018.02542] [PMID: 30483250]

[47]
Goropevšek, A.; Holcar, M.; Pahor, A.; Avčin, T. STAT signaling as a marker of SLE disease severity and implications for clinical therapy. Autoimmun. Rev.,  2019, 18(2), 144-154.
 [http://dx.doi.org/10.1016/j.autrev.2018.08.010] [PMID: 30572141]

[48]
Hirano, T.; Ishihara, K.; Hibi, M. Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene,  2000, 19(21), 2548-2556.
 [http://dx.doi.org/10.1038/sj.onc.1203551] [PMID: 10851053]

[49]
Phan, A.N.H.; Hua, T.N.M.; Kim, M.K.; Vo, V.T.A.; Choi, J.W.; Kim, H.W.; Rho, J.K.; Kim, K.W.; Jeong, Y. Gallic acid inhibition of Src-Stat3 signaling overcomes acquired resistance to EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer. Oncotarget,  2016, 7(34), 54702-54713.
 [http://dx.doi.org/10.18632/oncotarget.10581] [PMID: 27419630]

[50]
Kurinna, S.; Schäfer, M.; Ostano, P.; Karouzakis, E.; Chiorino, G.; Bloch, W.; Bachmann, A.; Gay, S.; Garrod, D.; Lefort, K.; Dotto, G.P.; Beer, H.D.; Werner, S. A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes. Nat. Commun.,  2014, 5(1), 5099.
 [http://dx.doi.org/10.1038/ncomms6099] [PMID: 25283360]

[51]
Sporn, M.B.; Liby, K.T. NRF2 and cancer: The good, the bad and the importance of context. Nat. Rev. Cancer,  2012, 12(8), 564-571.
 [http://dx.doi.org/10.1038/nrc3278] [PMID: 22810811]

[52]
Xu, C.; Huang, M.T.; Shen, G.; Yuan, X.; Lin, W.; Khor, T.O.; Conney, A.H.; Kong, A.N.T. Inhibition of 7,12-dimethylbenz(a)anthracene-induced skin tumorigenesis in C57BL/6 mice by sulforaphane is mediated by nuclear factor E2-related factor 2. Cancer Res.,  2006, 66(16), 8293-8296.
 [http://dx.doi.org/10.1158/0008-5472.CAN-06-0300] [PMID: 16912211]

[53]
Wondrak, G.T.; Cabello, C.M.; Villeneuve, N.F.; Zhang, S.; Ley, S.; Li, Y.; Sun, Z.; Zhang, D.D. Cinnamoyl-based Nrf2-activators targeting human skin cell photo-oxidative stress. Free Radic. Biol. Med.,  2008, 45(4), 385-395.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2008.04.023] [PMID: 18482591]

[54]
Schäfer, M.; Dütsch, S.; auf dem Keller, U.; Navid, F.; Schwarz, A.; Johnson, D.A.; Johnson, J.A.; Werner, S. Nrf2 establishes a glutathione-mediated gradient of UVB cytoprotection in the epidermis. Genes Dev.,  2010, 24(10), 1045-1058.
 [http://dx.doi.org/10.1101/gad.568810] [PMID: 20478997]

[55]
Rojo de la Vega, M.; Krajisnik, A.; Zhang, D.; Wondrak, G. Targeting NRF2 for improved skin barrier function and photoprotection: focus on the achiote-derived apocarotenoid bixin. Nutrients,  2017, 9(12), 1371.
 [http://dx.doi.org/10.3390/nu9121371] [PMID: 29258247]

[56]
Gills, J.J.; Jeffery, E.H.; Matusheski, N.V.; Moon, R.C.; Lantvit, D.D.; Pezzuto, J.M. Sulforaphane prevents mouse skin tumorigenesis during the stage of promotion. Cancer Lett.,  2006, 236(1), 72-79.
 [http://dx.doi.org/10.1016/j.canlet.2005.05.007] [PMID: 15993536]

[57]
Dinkova-Kostova, A.T.; Jenkins, S.N.; Fahey, J.W.; Ye, L.; Wehage, S.L.; Liby, K.T.; Stephenson, K.K.; Wade, K.L.; Talalay, P. Protection against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extracts. Cancer Lett.,  2006, 240(2), 243-252.
 [http://dx.doi.org/10.1016/j.canlet.2005.09.012] [PMID: 16271437]

[58]
Metz, I.; Traffehn, S.; Straßburger-Krogias, K.; Keyvani, K.; Bergmann, M.; Nolte, K.; Weber, M.S.; Bartsch, T.; Gold, R.; Brück, W. Glial cells express nuclear nrf2 after fumarate treatment for multiple sclerosis and psoriasis. Neurol. Neuroimmunol. Neuroinflamm.,  2015, 2(3), e99.
 [http://dx.doi.org/10.1212/NXI.0000000000000099] [PMID: 25866832]

[59]
Gruber, F; Ornelas, CM; Karner, S; Narzt, MS; Nagelreiter, IM; Gschwandtner, M Nrf2 deficiency causes lipid oxidation, inflammation, and matrix-protease expression in DHA-supplemented and UVA-irradiated skin fibroblasts. Free Radic Biol Med.,  2015, 88((PtB)), 439-451.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2015.05.006] [PMID: 25981373]

[60]
Kim, Y.R.; Oh, J.E.; Kim, M.S.; Kang, M.R.; Park, S.W.; Han, J.Y.; Eom, H.S.; Yoo, N.J.; Lee, S.H. Oncogenic NRF2 mutations in squamous cell carcinomas of oesophagus and skin. J. Pathol.,  2010, 220(4), 446-451.
 [http://dx.doi.org/10.1002/path.2653] [PMID: 19967722]

[61]
Rotblat, B.; Melino, G.; Knight, R.A. NRF2 and p53: Januses in cancer? Oncotarget,  2012, 3(11), 1272-1283.
 [http://dx.doi.org/10.18632/oncotarget.754] [PMID: 23174755]

[62]
Schäfer, M.; Farwanah, H.; Willrodt, A.H.; Huebner, A.J.; Sandhoff, K.; Roop, D.; Hohl, D.; Bloch, W.; Werner, S. Nrf2 links epidermal barrier function with antioxidant defense. EMBO Mol. Med.,  2012, 4(5), 364-379.
 [http://dx.doi.org/10.1002/emmm.201200219] [PMID: 22383093]

[63]
Wakabayashi, N.; Itoh, K.; Wakabayashi, J.; Motohashi, H.; Noda, S.; Takahashi, S.; Imakado, S.; Kotsuji, T.; Otsuka, F.; Roop, D.R.; Harada, T.; Engel, J.D.; Yamamoto, M. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat. Genet.,  2003, 35(3), 238-245.
 [http://dx.doi.org/10.1038/ng1248] [PMID: 14517554]

[64]
Taguchi, K.; Maher, J.M.; Suzuki, T.; Kawatani, Y.; Motohashi, H.; Yamamoto, M. Genetic analysis of cytoprotective functions supported by graded expression of Keap1. Mol. Cell. Biol.,  2010, 30(12), 3016-3026.
 [http://dx.doi.org/10.1128/MCB.01591-09] [PMID: 20404090]

[65]
Schäfer, M.; Willrodt, A.H.; Kurinna, S.; Link, A.S.; Farwanah, H.; Geusau, A.; Gruber, F.; Sorg, O.; Huebner, A.J.; Roop, D.R.; Sandhoff, K.; Saurat, J.H.; Tschachler, E.; Schneider, M.R.; Langbein, L.; Bloch, W.; Beer, H.D.; Werner, S. Activation of Nrf2 in keratinocytes causes chloracne (MADISH)‐like skin disease in mice. EMBO Mol. Med.,  2014, 6(4), 442-457.
 [http://dx.doi.org/10.1002/emmm.201303281] [PMID: 24503019]

[66]
Endo, H.; Sugioka, Y.; Nakagi, Y.; Saijo, Y.; Yoshida, T. A novel role of the NRF2 transcription factor in the regulation of arsenite-mediated keratin 16 gene expression in human keratinocytes. Environ. Health Perspect.,  2008, 116(7), 873-879.
 [http://dx.doi.org/10.1289/ehp.10696] [PMID: 18629308]

[67]
van der Kammen, R.; Song, J.Y.; de Rink, I.; Janssen, H.; Madonna, S.; Scarponi, C.; Albanesi, C.; Brugman, W.; Innocenti, M. Knockout of the Arp2/3 complex in epidermis causes a psoriasislike disease hallmarked by hyperactivation of transcription factor Nrf2. Development,  2017, 144(24), dev.156323.
 [http://dx.doi.org/10.1242/dev.156323] [PMID: 29113991]

[68]
Roberts, A.T.; Martin, C.K.; Liu, Z.; Amen, R.J.; Woltering, E.A.; Rood, J.C.; Caruso, M.K.; Yu, Y.; Xie, H.; Greenway, F.L. The safety and efficacy of a dietary herbal supplement and gallic acid for weight loss. J. Med. Food,  2007, 10(1), 184-188.
 [http://dx.doi.org/10.1089/jmf.2006.272] [PMID: 17472485]

[69]
Ferk, F.; Kundi, M.; Brath, H.; Szekeres, T.; Al-Serori, H.; Mišík, M.; Saiko, P.; Marculescu, R.; Wagner, K.H.; Knasmueller, S. Gallic acid improves health-associated biochemical parameters and prevents oxidative damage of DNA in type 2 diabetes patients: Results of a placebo-controlled pilot study. Mol. Nutr. Food Res.,  2018, 62(4), 1700482.
 [http://dx.doi.org/10.1002/mnfr.201700482] [PMID: 29193677]

[70]
Fairus, S.; Leow, S.S.; Mohamed, I.N.; Tan, Y.A.; Sundram, K.; Sambanthamurthi, R. A phase I single-blind clinical trial to evaluate the safety of oil palm phenolics (OPP) supplementation in healthy volunteers. Sci. Rep.,  2018, 8(1), 8217.
 [http://dx.doi.org/10.1038/s41598-018-26384-7] [PMID: 29844318]

[71]
Choi, Y.; Lee, J.H.; Kwon, H.B.; An, S.; Lee, A.Y. Skin testing of gallic acid-based hair dye in paraphenylenediamine/paratoluenediamine-reactive patients. J. Dermatol.,  2016, 43(7), 795-798.
 [http://dx.doi.org/10.1111/1346-8138.13226] [PMID: 26663148]
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DOI https://dx.doi.org/10.2174/1570180820666230314103222	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X
Letters in Drug Design & Discovery

The Anti-psoriatic Effect of Gallic Acid is Associated with the Suppression of Keratin 6 and Nrf2

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