{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:13:18Z","timestamp":1788797598346,"version":"build-2803163510"},"reference-count":166,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The nuclear factor erythroid 2\u2013related factor 2 (NRF2) is a master transcription factor that orchestrates cellular defense against oxidative and electrophilic stress. Dysregulation of the KEAP1\u2013NRF2\u2013ARE pathway has been implicated in several dermatological disorders, including vitiligo, psoriasis, atopic dermatitis, photoaging, and radiation dermatitis. This review summarizes recent advances in the understanding of NRF2 activation mechanisms and highlights pharmacological and natural compounds with potential dermatological applications. A comprehensive analysis of natural, semisynthetic, and synthetic NRF2 modulators is provided, describing their chemical structures, synthetic approaches, mechanisms of action, preclinical and clinical evidence, and therapeutic relevance for skin disorders. Multiple classes of NRF2 activators, including isothiocyanates such as sulforaphane, triterpenoids such as omaveloxolone, flavonoids including baicalein and apigenin, alkaloids such as berberine, glycosides like afzelin and paeoniflorin, stilbenoids such as tapinarof, and \u03b1,\u03b2-unsaturated fumaric acid esters such as dimethyl fumarate, have demonstrated antioxidant, anti-inflammatory, and cytoprotective effects in keratinocytes and melanocytes. Some of these agents, particularly dimethyl fumarate and tapinarof, have advanced to clinical development or commercialization, whereas others remain at the preclinical stage but show encouraging results in animal models and cell culture systems. Overall, pharmacological activation of NRF2 represents a promising therapeutic strategy to counteract oxidative stress\u2013driven skin damage and inflammation; however, continued translational and clinical research is required to optimize formulations, dosing regimens, and safety profiles for integration into dermatological practice.<\/jats:p>","DOI":"10.3390\/ph19030497","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:03:27Z","timestamp":1773756207000},"page":"497","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["NRF2 as a Therapeutic Target in Dermatological Disorders: Mechanisms and Molecules"],"prefix":"10.3390","volume":"19","author":[{"given":"Ismael","family":"Khiar-Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Dermatology Department, Hospital Universitario Virgen del Roc\u00edo, 41013 Sevilla, Spain"},{"name":"Medicine Department, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2195-5183","authenticated-orcid":false,"given":"Nora","family":"Khiar-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Qu\u00edmica, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6843-5877","authenticated-orcid":false,"given":"Jos\u00e9-Juan","family":"Pereyra-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Dermatology Department, Hospital Universitario Virgen del Roc\u00edo, 41013 Sevilla, Spain"},{"name":"Medicine Department, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3468-387X","authenticated-orcid":false,"given":"Inmaculada","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1152\/physrev.00023.2017","article-title":"The KEAP1\u2013NRF2 system: A thiol-based sensor\u2013effector apparatus for maintaining redox homeostasis","volume":"98","author":"Yamamoto","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1101\/gad.13.1.76","article-title":"KEAP1 represses nuclear activation of antioxidant responsive elements by NRF2 through binding to the amino-terminal Neh2 domain","volume":"13","author":"Itoh","year":"1999","journal-title":"Genes Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7130","DOI":"10.1128\/MCB.24.16.7130-7139.2004","article-title":"Oxidative stress sensor KEAP1 functions as an adaptor for CUL3-based e3 ligase to regulate proteasomal degradation of NRF2","volume":"24","author":"Kobayashi","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10941","DOI":"10.1128\/MCB.24.24.10941-10953.2004","article-title":"KEAP1 is a redox-regulated substrate adaptor protein for a CUL3-dependent ubiquitin ligase complex","volume":"24","author":"Zhang","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.freeradbiomed.2022.06.238","article-title":"NRF2 in dermatological disorders: Pharmacological activation for protection against cutaneous photodamage and photodermatosis","volume":"188","author":"Kahremany","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11624","DOI":"10.1038\/ncomms11624","article-title":"NRF2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription","volume":"7","author":"Kobayashi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.tips.2022.12.003","article-title":"Advances and challenges in therapeutic targeting of NRF2","volume":"44","author":"Copple","year":"2023","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nature10189","article-title":"Oncogene-induced NRF2 transcription promotes ROS detoxification and tumorigenesis","volume":"475","author":"DeNicola","year":"2011","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1158\/0008-5472.CAN-12-3386","article-title":"RXR\u03b1 inhibits the NRF2\u2013ARE signaling pathway through a direct interaction with the neh7 domain of NRF2","volume":"73","author":"Wang","year":"2013","journal-title":"Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1073\/pnas.0307301101","article-title":"Protection against electrophile and oxidant stress by induction of the phase 2 response: Fate of cysteines of the keap1 sensor modified by inducers","volume":"101","author":"Wakabayashi","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.molcel.2013.08.003","article-title":"Phosphorylation of p62 activates the KEAP1-NRF2 pathway during selective autophagy","volume":"51","author":"Ichimura","year":"2013","journal-title":"Mol. Cell."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14841","DOI":"10.1074\/jbc.M513737200","article-title":"Glycogen synthase kinase-3\u03b2 inhibits the xenobiotic and antioxidant cell response by direct phosphorylation and nuclear exclusion of the transcription factor NRF2","volume":"281","author":"Salazar","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15244","DOI":"10.1074\/jbc.M113.540633","article-title":"Transcription factors NRF2 and NF-\u03baB are coordinated effectors of the Rho family, GTP-binding protein RAC1 during Inflammation","volume":"289","author":"Cuadrado","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1089\/ars.2010.3216","article-title":"When NRF2 talks, who\u2019s listening?","volume":"13","author":"Wakabayashi","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/s41419-023-06234-9","article-title":"Sulforaphane alleviates psoriasis by enhancing antioxidant defense through KEAP1-NRF2 pathway activation and attenuating inflammatory signaling","volume":"14","author":"Ma","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.jid.2022.08.048","article-title":"Quantitative proteomics identifies reduced NRF2 activity and mitochondrial dysfunction in atopic dermatitis","volume":"143","author":"Koch","year":"2023","journal-title":"J. Investig. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.4049\/jimmunol.1801065","article-title":"Cutting edge: NRF2 regulates neutrophil recruitment and accumulation in skin during contact hypersensitivity","volume":"202","author":"Helou","year":"2019","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1038\/jid.2011.56","article-title":"Heme oxygenase-1 protects human melanocytes from H2O2-induced oxidative stress via the NRF2-ARE pathway","volume":"131","author":"Jian","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1111\/jcmm.12874","article-title":"Genetic polymorphism of the NRF2 promoter region is associated with vitiligo risk in han chinese populations","volume":"20","author":"Song","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1128\/MCB.01204-10","article-title":"SCF\/\u03b2-TrCP promotes glycogen synthase kinase 3-dependent degradation of the NRF2 transcription factor in a KEAP1-independent manner","volume":"31","author":"Rada","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17500","DOI":"10.1073\/pnas.0708710104","article-title":"Sulforaphane mobilizes cellular defenses that protect skin against damage by UV radiation","volume":"104","author":"Talalay","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.freeradbiomed.2015.08.028","article-title":"Systemic administration of the apocarotenoid bixin protects skin against solar UV-induced damage through activation of NRF2","volume":"89","author":"Tao","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rojo de la Vega, M., Zhang, D.D., and Wondrak, G.T. (2018). Topical bixin confers NRF2-dependent protection against photodamage and hair graying in mouse skin. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00287"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/j.cell.2016.05.017","article-title":"Repression of the antioxidant NRF2 pathway in premature aging","volume":"165","author":"Kubben","year":"2016","journal-title":"Cell"},{"key":"ref_25","unstructured":"National Institutes of Helath (2014). RTA-408 Lotion in Patients at Risk for Radiation Dermatitis (PRIMROSE), Identifier: NCT02142959."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.29245\/2572-9411\/2017\/3.1109","article-title":"NRF2 activators as therapy for acute radiation dermatitis","volume":"2","author":"Nakagami","year":"2017","journal-title":"J. Rare Dis. Res. Treat."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5492","DOI":"10.1128\/MCB.22.15.5492-5505.2002","article-title":"NRF2 transcription factor, a novel target of keratinocyte growth factor action which regulates gene expression and accelerates cutaneous wound healing","volume":"22","author":"Braun","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1530\/JME-18-0102","article-title":"Dimethyl fumarate accelerates wound healing under diabetic condition","volume":"61","author":"Li","year":"2018","journal-title":"J. Mol. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Li, M., Yu, H., Pan, H., Zhou, X., Ruan, Q., Kong, D., Chu, Z., Li, H., Huang, J., and Huang, X. (2019). NRF2 suppression delays diabetic wound healing through sustained oxidative stress and inflammation. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01099"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"25258","DOI":"10.1038\/s41598-024-75786-3","article-title":"Non-electrophilic NRF2 activators promote wound healing in human keratinocytes and diabetic mice and demonstrate selective downstream gene targeting","volume":"14","author":"Barakat","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kavian, N., Servettaz, A., Weill, B., and Batteux, F. (2018). The NRF2\u2013antioxidant response element signaling pathway controls fibrosis and autoimmunity in scleroderma. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01896"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113846","DOI":"10.1016\/j.bcp.2020.113846","article-title":"NRF2 in keratinocytes protects against skin fibrosis via regulating epidermal lesion and inflammatory response","volume":"174","author":"Wu","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1158\/1940-6207.CAPR-14-0362","article-title":"NRF2 activation protects against solar-simulated ultraviolet radiation in mice and humans","volume":"8","author":"Knatko","year":"2015","journal-title":"Cancer Prev. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8293","DOI":"10.1158\/0008-5472.CAN-06-0300","article-title":"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","volume":"66","author":"Xu","year":"2006","journal-title":"Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1101\/gad.568810","article-title":"NRF2 establishes a glutathione-mediated gradient of UVB cytoprotection in the epidermis","volume":"24","author":"Navid","year":"2010","journal-title":"Genes Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1128\/MCB.26.10.3773-3784.2006","article-title":"NRF transcription factors in keratinocytes are essential for skin tumor prevention but not for wound healing","volume":"26","author":"Huber","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13568","DOI":"10.1073\/pnas.0806268105","article-title":"Cancer related mutations in NRF2 impair its recognition by KEAP1-CUL3 E3 ligase and promote malignancy","volume":"105","author":"Shibata","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","first-page":"3","article-title":"Oxidative stress in lichen planus","volume":"19","author":"Aly","year":"2010","journal-title":"Acta Dermatovenerol. APA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.aller.2010.06.012","article-title":"Oxidative stress status in patients with chronic idiopathic urticaria","volume":"39","author":"Sagdic","year":"2011","journal-title":"Allergol. Immunopathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.jaad.2016.10.042","article-title":"Increased interleukin (IL)-17 serum levels in patients with hidradenitis suppurativa: Implications for treatment with anti-IL-17 agents","volume":"76","author":"Matusiak","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e00099-20","DOI":"10.1128\/MCB.00099-20","article-title":"The molecular mechanisms regulating the KEAP1\u2013NRF2 pathway","volume":"40","author":"Baird","year":"2020","journal-title":"Mol. Cell. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/emmm.201200219","article-title":"NRF2 links epidermal barrier function with antioxidant defense","volume":"4","author":"Farwanah","year":"2012","journal-title":"EMBO Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ccell.2018.03.022","article-title":"NRF2 and the hallmarks of cancer","volume":"34","author":"Chapman","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.freeradbiomed.2015.04.018","article-title":"NRF2\u2014A regulator of keratinocyte redox signaling","volume":"88","author":"Werner","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s00403-015-1554-2","article-title":"The role of transcription factor NRF2 in skin cells metabolism","volume":"307","author":"Skrzydlewska","year":"2015","journal-title":"Arch. Dermatol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.lfs.2007.01.034","article-title":"Extract of ginkgo biloba induces phase 2 genes through KEAP1\u2013NRF2\u2013ARE signaling pathway","volume":"80","author":"Liu","year":"2007","journal-title":"Life Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5193","DOI":"10.1111\/jcmm.14393","article-title":"Ginkgo biloba extract protects human melanocytes from H2O2-induced oxidative stress by activating NRF2","volume":"23","author":"Zhang","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jdermsci.2014.04.001","article-title":"EGb-761 prevents ultraviolet B-induced photoaging via inactivation of mitogen-activated protein kinases and proinflammatory cytokine expression","volume":"75","author":"Chen","year":"2014","journal-title":"J. Dermatol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1046\/j.1365-2230.2003.01207.x","article-title":"Effectiveness of oral ginkgo biloba in treating limited, slowly spreading vitiligo","volume":"28","author":"Parsad","year":"2003","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Szczurko, O., Shear, N.H., Taddio, A., and Boon, H. (2011). Ginkgo biloba for the treatment of vitiligo vulgaris: An open-label pilot clinical trial. BMC Complement. Altern. Med., 11.","DOI":"10.1186\/1472-6882-11-21"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1016\/j.jid.2017.05.004","article-title":"Tapinarof is a natural AhR agonist that resolves skin inflammation in mice and humans","volume":"137","author":"Smith","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_52","first-page":"232","article-title":"Synthesis of (E)-3,5-dihydroxy-4-isopropylstilbene under microwave irradiation","volume":"6","author":"Zhang","year":"2014","journal-title":"J. Chem. Pharm. Res."},{"key":"ref_53","unstructured":"Andrews, I.P., Calandra, N., Davis, T.A., and Sudini, R.R. (2020). Process for Preparing Tapinarof. (US 10647649B2), U.S. Patent."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"117559","DOI":"10.1016\/j.taap.2025.117559","article-title":"Dual activation of AhR and NRF2 pathways by the natural stilbenoid tapinarof protects against particulate matter-induced skin barrier dysfunction","volume":"505","author":"Lin","year":"2025","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaci.2023.12.013","article-title":"Tapinarof validates the aryl hydrocarbon receptor as a therapeutic target: A clinical review","volume":"154","author":"Silverberg","year":"2024","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1056\/NEJMoa2103629","article-title":"Phase 3 trials of tapinarof cream for plaque psoriasis","volume":"385","author":"Lebwohl","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_57","unstructured":"U.S. Food and Drug Administration (2024). VTAMA (Tapinarof) Cream, 1%: Prescribing Information, Dermavant Sciences, Inc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1021\/acs.oprd.0c00503","article-title":"Dimethyl fumarate: Heterogeneous catalysis for the development of an innovative flow synthesis","volume":"25","author":"Piccolo","year":"2021","journal-title":"Org. Process Res. Dev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1039\/C9RA09119J","article-title":"Continuous-flow synthesis of dimethyl fumarate: A powerful small molecule for the treatment of psoriasis and multiple sclerosis","volume":"10","author":"Lima","year":"2020","journal-title":"RSC Adv."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1093\/brain\/awq386","article-title":"Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the NRF2 antioxidant pathway","volume":"134","author":"Linker","year":"2011","journal-title":"Brain"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/bjd.14947","article-title":"Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate-to-severe chronic plaque psoriasis: A randomized, double-blind, Fumaderm\u00ae- and placebo-controlled trial (BRIDGE)","volume":"176","author":"Mrowietz","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/sj.jid.5700686","article-title":"Dimethyl fumarate induces immunosuppression via glutathione depletion and subsequent induction of heme oxygenase 1","volume":"127","author":"Listopad","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s10593-005-0169-5","article-title":"New procedure for obtaining indomethacin","volume":"41","author":"Magedov","year":"2005","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.immuni.2022.04.015","article-title":"Activation of the transcription factor NRF2 mediates the anti-inflammatory properties of a subset of over-the-counter and prescription NSAIDs","volume":"55","author":"Eisenstein","year":"2022","journal-title":"Immunity"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/j.1365-2133.1986.tb06240.x","article-title":"A quantitative study of the effect of topical indomethacin on cutaneous erythema induced by UVB and UVC radiation","volume":"115","author":"Farr","year":"1986","journal-title":"Br. J. Dermatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"J10","DOI":"10.1016\/0002-9149(88)90002-1","article-title":"Discovery, biochemistry and biology of lovastatin","volume":"62","author":"Alberts","year":"1988","journal-title":"Am. J. Cardiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"484","DOI":"10.2183\/pjab.86.484","article-title":"A historical perspective on the discovery of statins","volume":"86","author":"Endo","year":"2010","journal-title":"Proc. Jpn. Acad. Ser. B"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.chembiol.2009.09.017","article-title":"Directed evolution and structural characterization of a simvastatin synthase","volume":"16","author":"Gao","year":"2009","journal-title":"Chem. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev.pharmtox.45.120403.095748","article-title":"Pleiotropic effects of statins","volume":"45","author":"Liao","year":"2005","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1016\/j.jid.2017.01.020","article-title":"Simvastatin protects human melanocytes from H2O2-induced oxidative stress by activating NRF2","volume":"137","author":"Chang","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jaad.2016.06.015","article-title":"A double-blind, placebo-controlled, phase-II clinical trial to evaluate oral simvastatin as a treatment for vitiligo","volume":"76","author":"Vanderweil","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_72","unstructured":"Wehrli, C. (1995). Method for the Production of Folic Acid Using a Novel Diimine Intermediate. (US5410056A), U.S. Patent."},{"key":"ref_73","unstructured":"Wang, G., Zhang, J., and Wang, S. (2016). Folic Acid Synthesis Method. (CN106046005A), China Patent."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.ymben.2016.10.011","article-title":"Folic acid production by engineered ashbya gossypii","volume":"38","author":"Ros","year":"2016","journal-title":"Metab. Eng."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1608586","DOI":"10.1155\/2021\/1608586","article-title":"Folic acid protects melanocytes from oxidative stress via activation of NRF2 and inhibition of HMGB1","volume":"2021","author":"Du","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"460","DOI":"10.2340\/000155555577460462","article-title":"Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure","volume":"77","author":"Juhlin","year":"1997","journal-title":"Acta Derm. Venereol."},{"key":"ref_77","unstructured":"Anderson, E., Decker, A., and Liu, X. (2015). 2,2-Difluoropropionamide Derivatives of Bardoxolone Methyl, Polymorphic Forms and Methods of Use Thereof. (US20150259377A1), U.S. Patent."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1667\/RR13578.1","article-title":"Topical application of the synthetic triterpenoid RTA 408 protects mice from radiation-induced dermatitis","volume":"181","author":"Reisman","year":"2014","journal-title":"Radiat. Res."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Reisman, S.A., Goldsberry, A.R., Lee, C.-Y.I., O\u2019Grady, M.L., Proksch, J.W., Ward, K.W., and Meyer, C.J. (2015). Topical application of RTA 408 lotion activates NRF2 in human skin and is well-tolerated by healthy human volunteers. BMC Dermatol., 15.","DOI":"10.1186\/s12895-015-0029-7"},{"key":"ref_80","unstructured":"U.S. Food and Drug Administration (2023). Skyclarys (Omaveloxolone) Prescribing Information."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1073\/pnas.89.6.2399","article-title":"A major inducer of anticarcinogenic protective enzymes from broccoli: Isolation and elucidation of structure","volume":"89","author":"Zhang","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0031-9422(00)00316-2","article-title":"The chemical diversity and distribution of glucosinolates and isothiocyanates among plants","volume":"56","author":"Fahey","year":"2001","journal-title":"Phytochemistry"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.molmed.2012.04.003","article-title":"Glucosinolates and isothiocyanates in health and disease","volume":"18","author":"Kostov","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6975","DOI":"10.3390\/molecules19066975","article-title":"Novel gram-scale production of enantiopure R-sulforaphane from Tuscan black kale seeds","volume":"19","author":"Rollin","year":"2014","journal-title":"Molecules"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/S0223-5234(03)00141-7","article-title":"Synthesis of isothiocyanate-derived mercapturic acids","volume":"38","author":"Vermeulen","year":"2003","journal-title":"Eur. J. Med. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"8548","DOI":"10.1158\/0008-5472.CAN-05-0237","article-title":"Phenethyl isothiocyanate and sulforaphane and their n-acetylcysteine conjugates inhibit malignant progression of lung adenomas induced by tobacco carcinogens in A\/J mice","volume":"65","author":"Conaway","year":"2005","journal-title":"Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.1055\/s-0031-1289601","article-title":"New method for the synthesis of sulforaphane and related isothiocyanates","volume":"24","author":"Chen","year":"2011","journal-title":"Synthesis"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1021\/jo00082a016","article-title":"Asymmetric synthesis of chiral sulfinate esters and sulfoxides. Synthesis of sulforaphane","volume":"59","author":"Whitesell","year":"1994","journal-title":"J. Org. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"6789","DOI":"10.1021\/jo00051a022","article-title":"Asymmetric synthesis of alkane- and arenesulfinates of diacetone-D-glucose (DAG): An improved and general route to both enantiomerically pure sulfoxides","volume":"57","author":"Khiar","year":"1992","journal-title":"J. Org. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"6002","DOI":"10.1021\/jo9007749","article-title":"Enantiopure sulforaphane analogues with various substituents at the sulfinyl sulfur: Asymmetric synthesis and biological activities","volume":"74","author":"Khiar","year":"2009","journal-title":"J. Org. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Alcarranza, M., Villegas, I., Mu\u00f1oz-Garc\u00eda, R., Recio, R., Fern\u00e1ndez, I., and Alarc\u00f3n-de-la-Lastra, C. (2022). Immunomodulatory effects of (R)-sulforaphane on LPS-activated murine immune cells: Molecular signaling pathways and epigenetic changes in histone markers. Pharmaceuticals, 15.","DOI":"10.3390\/ph15080966"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.ejmech.2014.09.052","article-title":"Sulforaphane homologues: Enantiodivergent synthesis of both enantiomers, activation of the NRF2 transcription factor and selective cytotoxic activity","volume":"87","author":"Elhalem","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"21520","DOI":"10.1021\/acs.jafc.4c02943","article-title":"Immunomodulatory effects and regulatory mechanisms of (R)-6-HITC, an isothiocyanate from wasabi (Eutrema japonicum), in an ex vivo mouse model of LPS-induced inflammation","volume":"72","author":"Alcarranza","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7270","DOI":"10.1039\/D3FO02009F","article-title":"(R)-8-Methylsulfinyloctyl isothiocyanate from Nasturtium officinale inhibits LPS-induced immunoinflammatory responses in mouse peritoneal macrophages: Chemical synthesis and molecular signaling pathways involved","volume":"14","author":"Alcarranza","year":"2023","journal-title":"Food Funct."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/chem.19970030510","article-title":"Synthesis of (R)-sulforaphane using [CpRu((R,R)-CHIRAPHOS)]+ as chiral auxiliary","volume":"3","author":"Schenk","year":"1997","journal-title":"Chem. Eur. J."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1021\/jm00027a021","article-title":"Design and synthesis of bifunctional isothiocyanate analogs of sulforaphane: Correlation between structure and potency as inducers of anticarcinogenic detoxication enzymes","volume":"37","author":"Posner","year":"1994","journal-title":"J. Med. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Janczewski, \u0141. (2022). Sulforaphane and Its bifunctional analogs: Synthesis and biological activity. Molecules, 27.","DOI":"10.3390\/molecules27051750"},{"key":"ref_98","first-page":"332","article-title":"New enantiomeric fluorine-containing derivatives of sulforaphane: Synthesis, absolute configurations and biological activity","volume":"61","author":"Wiktorska","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"103454","DOI":"10.1016\/j.bioorg.2019.103454","article-title":"Fluoroaryl analogs of sulforaphane\u2014A group of compounds of anticancer and antimicrobial activity","volume":"94","author":"Kwiatkowska","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1021\/acs.bioconjchem.8b00808","article-title":"First examples of H2S-releasing glycoconjugates: Stereoselective synthesis and anticancer activities","volume":"30","author":"Fortunato","year":"2019","journal-title":"Bioconjug. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"117469","DOI":"10.1016\/j.ejmech.2025.117469","article-title":"Exploring the broad-spectrum activity of carbohydrate-based iberin analogues: From anticancer effect to antioxidant properties","volume":"289","author":"Prieto","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ejmech.2017.03.028","article-title":"Novel phosphonate analogs of sulforaphane: Synthesis, in vitro and in vivo activity","volume":"132","author":"Psurski","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_103","unstructured":"Khiar El Wahabi, N., Fern\u00e1ndez Fern\u00e1ndez, I., and Recio Jim\u00e9nez, R. (2015). Sulforaphane-Derived Compounds, Production Method Thereof and the Medical, Food and Cosmetic Use of Same. (US9884816B2), U.S. Patent."},{"key":"ref_104","unstructured":"Johns Hopkins University (2019). Effect of Topical Sulforaphane on Skin Aging and with Ultraviolet and Visible Light Exposure, Johns Hopkins University. NCT03730649."},{"key":"ref_105","unstructured":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (2018). Study to Evaluate the Effect of Sulforaphane in Broccoli Sprout Extract on Breast Tissue, Identifier: NCT00982319."},{"key":"ref_106","first-page":"1761","article-title":"Sulforaphane has a therapeutic effect in an atopic dermatitis murine model and activates the NRF2\/HO-1 axis","volume":"20","author":"Wu","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pharmthera.2014.04.006","article-title":"Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine","volume":"144","author":"Ohta","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1016\/j.jid.2019.03.1165","article-title":"Molecular hydrogen protects human melanocytes from oxidative stress by activating NRF2 signaling","volume":"140","author":"Fang","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jphotobiol.2011.09.006","article-title":"Hydrogen-rich electrolyzed warm water represses wrinkle formation against UVA ray together with type-I collagen production and oxidative-stress diminishment in fibroblasts and cell-injury prevention in keratinocytes","volume":"106","author":"Kato","year":"2012","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"353152","DOI":"10.1155\/2012\/353152","article-title":"Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases","volume":"2012","author":"Ohno","year":"2012","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1080\/02652030902942873","article-title":"The chemistry and analysis of annatto food colouring: A review","volume":"26","author":"Scotter","year":"2009","journal-title":"Food Addit. Contam. Part A"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Rojo de la Vega, M., Krajisnik, A., Zhang, D.D., and Wondrak, G.T. (2017). Targeting NRF2 for Improved Skin Barrier Function and Photoprotection: Focus on the Achiote-Derived Apocarotenoid Bixin. Nutrients, 9.","DOI":"10.3390\/nu9121371"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e8895","DOI":"10.7717\/peerj.8895","article-title":"Comparative transcriptomics characterized the distinct biosynthetic abilities of terpenoid and paeoniflorin biosynthesis in herbaceous peony strains","volume":"8","author":"Lu","year":"2020","journal-title":"PeerJ"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Boo, Y.C. (2020). Natural NRF2 modulators for skin protection. Antioxidants, 9.","DOI":"10.3390\/antiox9090812"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/jphp.13204","article-title":"Paeoniflorin: A monoterpene glycoside from plants of the paeoniaceae family with diverse anticancer activities","volume":"72","author":"Xiang","year":"2020","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"120366","DOI":"10.1016\/j.indcrop.2024.120366","article-title":"Green microextraction using deep eutectic solvents: Computer-aided analysis of bioactive components in natural products","volume":"224","author":"Wen","year":"2025","journal-title":"Ind. Crops. Prod."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Xu, P., Li, Q., Liang, W., Hu, Y., Chen, R., Lou, K., Zhan, L., Wu, X., and Pu, J. (2023). A tissue-specific profile of miRNAs and their targets related to paeoniaflorin and monoterpenoids biosynthesis in Paeonia lactiflora Pall. by transcriptome, small RNAs and degradome sequencing. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0279992"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Ye, Y., Pei, H., Cao, X., Liu, X., Li, Z., Wang, B., Pan, Y., and Zheng, J. (2023). The study of a novel paeoniflorin-converting enzyme from Cunninghamella blakesleeana. Molecules, 28.","DOI":"10.3390\/molecules28031289"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e14629","DOI":"10.1111\/cbdd.14629","article-title":"Synthesis, antioxidant activity, and molecular docking of novel paeoniflorin derivatives","volume":"104","author":"Ni","year":"2024","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1007\/s10753-019-01085-z","article-title":"Paeoniflorin prevents intestinal barrier disruption and inhibits lipopolysaccharide (LPS)-induced inflammation in Caco-2 cell monolayers","volume":"42","author":"Wu","year":"2019","journal-title":"Inflammation"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Lu, Y.-S., Jiang, Y., Yuan, J.-P., Jiang, S.-B., Yang, Y., Zhu, P.-Y., Sun, Y.-Z., Qi, R.-Q., Liu, T., and Wang, H.-X. (2020). UVA induced oxidative stress was inhibited by paeoniflorin\/NRF2 signaling or PLIN2. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00736"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.freeradbiomed.2025.03.043","article-title":"Paeoniflorin alleviated experimental Sj\u00f6gren\u2019s syndrome by inhibiting NLRP3 inflammasome activation of submandibular gland cells via activating NRF2\/HO-1 pathway","volume":"233","author":"Jiang","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1002\/ddr.21763","article-title":"Paeoniflorin inhibited nod-like receptor protein-3 inflammasome and NF-\u03baB-mediated inflammatory reactions in diabetic foot ulcer by inhibiting the chemokine receptor CXCR2","volume":"82","author":"Sun","year":"2021","journal-title":"Drug Dev. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s10067-018-4315-8","article-title":"The efficacy and safety of total glucosides of peony in the treatment of primary Sj\u00f6gren\u2019s syndrome: A multi-center, randomized, double-blinded, placebo-controlled clinical trial","volume":"38","author":"Liu","year":"2019","journal-title":"Clin. Rheumatol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.intimp.2013.01.021","article-title":"Reduced hepatotoxicity by total glucosides of paeony in combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis","volume":"15","author":"Chen","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.intimp.2015.08.008","article-title":"Total glucosides of paeony can reduce the hepatotoxicity caused by methotrexate and leflunomide combination treatment of active rheumatoid arthritis","volume":"28","author":"Xiang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1080\/13880209.2018.1492620","article-title":"A comprehensive review on phytochemistry, pharmacology, and flavonoid biosynthesis of Scutellaria baicalensis","volume":"56","author":"Wang","year":"2018","journal-title":"Pharm. Biol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.jep.2010.01.006","article-title":"The genus Scutellaria: An ethnopharmacological and phytochemical review","volume":"128","author":"Shang","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Nik Salleh, N.N.H., Othman, F.A., Kamarudin, N.A., and Tan, S.C. (2020). The biological activities and therapeutic potentials of baicalein extracted from Oroxylum indicum: A systematic review. Molecules, 25.","DOI":"10.3390\/molecules25235677"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/j.1348-0421.2005.tb03732.x","article-title":"Remarkable synergies between baicalein and tetracyclie, and baicalein and \u03b2-lactams against methicillin-resistant Staphylococcus aureus","volume":"49","author":"Fujita","year":"2005","journal-title":"Microbiol. Immunol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/BF02977773","article-title":"Fine tuning of a reported synthetic route for biologically active flavonoid, baicalein","volume":"30","author":"Kim","year":"2007","journal-title":"Arch. Pharm. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1080\/10286020903508416","article-title":"Total synthesis of baicalein","volume":"12","author":"Chen","year":"2010","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.freeradbiomed.2018.10.421","article-title":"Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor 2 (NRF2) signaling pathway","volume":"129","author":"Ma","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.freeradbiomed.2024.12.036","article-title":"Baicalein disrupts the KEAP1-NRF2 interaction to alleviate oxidative stress injury by inhibiting M1 macrophage polarization","volume":"227","author":"Chi","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.intimp.2010.06.020","article-title":"Therapeutic effects of baicalein on atopic dermatitis-like skin lesions of NC\/Nga mice induced by Dermatophagoides pteronyssinus","volume":"10","author":"Yun","year":"2010","journal-title":"Int. Immunopharmacol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ejphar.2011.04.033","article-title":"Effects of baicalein and wogonin isolated from Scutellaria baicalensis roots on skin damage in acute UVB-irradiated hairless mice","volume":"661","author":"Kimura","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1111\/cts.13063","article-title":"Safety, tolerability, and pharmacokinetics of oral baicalein tablets in healthy Chinese subjects: A single-center, randomized, double-blind, placebo-controlled multiple-ascending-dose study","volume":"14","author":"Li","year":"2021","journal-title":"Clin. Transl. Sci."},{"key":"ref_138","unstructured":"CSPC ZhongQi Pharmaceutical Technology Co., Ltd (2019). A Randomized, Double-Blind, Placebo-Controlled, Multicenter and Phase IIa Clinical Trial for the Effectiveness and Safety of Baicalein Tablets in the Treatment of Improve Other Aspects of Healthy Adult with Influenza Fever, CSPC ZhongQi Pharmaceutical Technology Co., Ltd.. Identifier: NCT03830684."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Neag, M.A., Mocan, A., Echeverr\u00eda, J., Pop, R.M., Bocsan, C.I., Cri\u0219an, G., and Buzoianu, A.D. (2018). Berberine: Botanical occurrence, traditional uses, extraction methods, and relevance in cardiovascular, metabolic, hepatic, and renal disorders. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00557"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"113289","DOI":"10.1016\/j.ejmech.2021.113289","article-title":"The total synthesis of berberine and selected analogues, and their evaluation as amyloid \u03b2 aggregation inhibitors","volume":"215","author":"Tajiri","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"154826","DOI":"10.1016\/j.tetlet.2023.154826","article-title":"Concise total syntheses of berberine and its analogues in multigram scale enabled by trifluoroacetic anhydride\u2013promoted decarbonylative-elimination reaction","volume":"132","author":"Yan","year":"2023","journal-title":"Tetrahedron Lett."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jdermsci.2019.03.007","article-title":"Berberine protects immortalized line of human melanocytes from H2O2 induced oxidative stress via activation of NRF2 and Mitf signaling pathway","volume":"94","author":"Jiang","year":"2019","journal-title":"J. Dermatol. Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"121523","DOI":"10.1016\/j.ijpharm.2022.121523","article-title":"Novel berberine loaded hyalurosomes as a promising nanodermatological treatment for vitiligo: Biochemical, biological and gene expression studies","volume":"615","author":"Elhalmoushy","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e12376","DOI":"10.1111\/jfbc.12376","article-title":"Apigenin: A current review on its beneficial biological activities","volume":"41","author":"Zhou","year":"2017","journal-title":"J. Food Biochem."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"162750","DOI":"10.1155\/2013\/162750","article-title":"Chemistry and Biological Activities of Flavonoids: An Overview","volume":"2013","author":"Kumar","year":"2013","journal-title":"Sci. World J."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"8615","DOI":"10.3390\/ijms13078615","article-title":"Green extraction of natural products: Concept and principles","volume":"13","author":"Chemat","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"7313","DOI":"10.3390\/molecules15107313","article-title":"Plant Phenolics: Extraction, analysis and their antioxidant and anticancer properties","volume":"15","author":"Dai","year":"2010","journal-title":"Molecules"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Tang, Q.-Q., Wang, Z.-D., An, X.-H., Zhou, X.-Y., Zhang, R.-Z., Zhan, X., Zhang, W., and Zhou, J. (2024). Apigenin ameliorates H2O2-induced oxidative damage in melanocytes through nuclear factor-E2-related factor 2 (NRF2) and phosphatidylinositol 3-kinase (PI3K)\/protein kinase B (Akt)\/mammalian target of rapamycin (mTOR) pathways and reducing the generation of reactive oxygen species (ROS) in zebrafish. Pharmaceuticals, 17.","DOI":"10.3390\/ph17101302"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"27965","DOI":"10.1021\/acs.jafc.4c08430","article-title":"Apigenin reduces lipid droplet accumulation in hepatocytes by enhancing chaperone-mediated autophagy via AMPK","volume":"72","author":"Lu","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"138","DOI":"10.55730\/1300-0152.2732","article-title":"Apigenin attenuates ischemia\u2013reperfusion-induced pulmonary ferroptosis and fibrosis by activating the NRF2\/HO-1\/GPX4 axis in mice","volume":"49","author":"Zhang","year":"2025","journal-title":"Turk. J. Biol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"100189","DOI":"10.1016\/j.dscb.2025.100189","article-title":"Protective effects of apigenin in neurodegeneration: An update on the potential mechanisms","volume":"17","author":"Mohammadkhanizadeh","year":"2025","journal-title":"Brain Disord."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"10","DOI":"10.20431\/2456-0022.0803002","article-title":"Harnessing flavonoids and nutraceuticals for vitiligo via targeting oxidative stress and neural\u2013melanocyte crosstalk","volume":"8","author":"Hassan","year":"2025","journal-title":"ARC J. Dermatol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s12192-020-01071-7","article-title":"Apigenin protects human melanocytes against oxidative damage by activation of the NRF2 pathway","volume":"25","author":"Zhang","year":"2020","journal-title":"Cell Stress Chaperones"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3945\/an.116.012948","article-title":"Flavones: Food sources, bioavailability, metabolism, and bioactivity","volume":"8","author":"Hostetler","year":"2017","journal-title":"Adv. Nutr."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1021\/np020442j","article-title":"Phenolic compounds from Nymphaea odorata","volume":"66","author":"Zhang","year":"2003","journal-title":"J. Nat. Prod."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1248\/cpb.c21-00398","article-title":"Evaluating the sun protection factor of cosmetic formulations containing afzelin","volume":"69","author":"Kim","year":"2021","journal-title":"Chem. Pharm. Bull."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Boo, Y.C. (2020). Emerging strategies to protect the skin from ultraviolet rays using plant-derived materials. Antioxidants, 9.","DOI":"10.3390\/antiox9070637"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.tplants.2005.09.007","article-title":"Plant secondary metabolism glycosyltransferases: The emerging functional analysis","volume":"10","author":"Gachon","year":"2005","journal-title":"Trends Plant Sci."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.pbi.2005.03.007","article-title":"Glycosyltransferases: Managers of small molecules","volume":"8","author":"Bowles","year":"2005","journal-title":"Curr. Opin. Plant Biol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1111\/exd.13277","article-title":"Melanocyte-protective effect of afzelin is mediated by the NRF2\u2013ARE signaling pathway via GSK-3\u03b2 inactivation","volume":"26","author":"Jung","year":"2017","journal-title":"Exp. Dermatol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1002\/jps.1116","article-title":"The stability of gingerol and shogaol in aqueous solutions","volume":"90","author":"Bhattarai","year":"2001","journal-title":"J. Pharm. Sci."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1248\/bpb1978.7.836","article-title":"Pharmacological studies on ginger. I. pharmacological actions of pungent constituents, (6)-gingerol and (6)-shogaol","volume":"7","author":"Suekawa","year":"1984","journal-title":"J. Pharmacobiodyn."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.foodchem.2016.07.106","article-title":"Efficient dehydration of 6-gingerol to 6-shogaol catalyzed by an acidic ionic liquid under ultrasound irradiation","volume":"215","author":"Kou","year":"2017","journal-title":"Food Chem."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.foodchem.2014.03.039","article-title":"Synthesis and quorum sensing inhibitory activity of key phenolic compounds of ginger and their derivatives","volume":"159","author":"Kumar","year":"2014","journal-title":"Food Chem."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Mak, K.-K., Zhang, S., Sakirolla, R., Balijepalli, M.K., Dinkova-Kostova, A.T., Epemolu, O., Mohd, Z., and Pichika, M.R. (2023). Synthesis of new shogaol analogues as NRF2 activators and evaluation of their anti-inflammatory activity, modes of action and metabolic stability. Antioxidants, 12.","DOI":"10.3390\/antiox12020475"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Yang, L., Yang, F., Teng, L., and Katayama, I. (2020). 6-Shogaol protects human melanocytes against oxidative stress through activation of the NRF2-antioxidant response element signaling pathway. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103537"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/497\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T05:11:46Z","timestamp":1773897106000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,17]]},"references-count":166,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ph19030497"],"URL":"https:\/\/doi.org\/10.3390\/ph19030497","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,17]]}}}