{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:27:07Z","timestamp":1790364427060,"version":"4.1.0"},"reference-count":93,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Resources and Engineering Research Council (NSERC) of Canada","doi-asserted-by":"publisher","award":["ALLRP 570618-21"],"award-info":[{"award-number":["ALLRP 570618-21"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Eczema (atopic dermatitis, AD) is a skin disease characterized by skin barrier dysfunction due to various factors, including genetics, immune system abnormalities, and environmental triggers. Application of emollients and topical drugs such as corticosteroids and calcineurin inhibitors form the mainstay of treatments for this challenging condition. This review aims to summarize the recent advances made in phytochemical-based topical applications to treat AD and the different carriers that are being used. In this review, the clinical efficacy of several plant extracts and bioactive phytochemical compounds in treating AD are discussed. The anti-atopic effects of the herbs are evident through improvements in the Scoring Atopic Dermatitis (SCORAD) index, reduced epidermal thickness, decreased transepidermal water loss, and alleviated itching and dryness in individuals affected by AD as well as in AD mouse models. Histopathological studies and serum analyses conducted in AD mouse models demonstrated a reduction in key inflammatory factors, including thymic stromal lymphopoietin (TSLP), serum immunoglobulin E (IgE), and interleukins (IL). Additionally, there was an observed upregulation of the filaggrin (FLG) gene, which regulates the proteins constituting the stratum corneum, the outermost layer of the epidermis. Carriers play a crucial role in topical drug applications, influencing dose delivery, retention, and bioavailability. This discussion delves into the efficacy of various nanocarriers, including liposomes, ethosomes, nanoemulsions, micelles, nanocrystals, solid-lipid nanoparticles, and polymeric nanoparticles. Consequently, the potential long-term side effects such as atrophy, eruptions, lymphoma, pain, and allergic reactions that are associated with current topical treatments, including emollients, topical corticosteroids, topical calcineurin inhibitors, and crisaborole, can potentially be mitigated through the use of phytochemical-based natural topical treatments.<\/jats:p>","DOI":"10.3390\/ijms25105375","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T03:35:55Z","timestamp":1715744155000},"page":"5375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Recent Advances in Phytochemical-Based Topical Applications for the Management of Eczema: A Review"],"prefix":"10.3390","volume":"25","author":[{"given":"Janani","family":"Radhakrishnan","sequence":"first","affiliation":[{"name":"Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry E.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 2Y9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin B.","family":"Noftall","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 2Y9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carman A.","family":"Giacomantonio","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 2Y9, Canada"},{"name":"Department of Surgery, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 2Y9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3435-0052","authenticated-orcid":false,"given":"H. P. Vasantha","family":"Rupasinghe","sequence":"additional","affiliation":[{"name":"Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada"},{"name":"Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 2Y9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000370220","article-title":"Atopic Dermatitis: Global Epidemiology and Risk Factors","volume":"66","author":"Nutten","year":"2015","journal-title":"Ann. Nutr. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1542\/peds.2004-0374","article-title":"Effects of Atopic Dermatitis on Young American Children and Their Families","volume":"114","author":"Chamlin","year":"2004","journal-title":"Pediatrics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.jid.2017.01.030","article-title":"Increased Risk of Cutaneous and Systemic Infections in Atopic Dermatitis\u2014A Cohort Study","volume":"137","author":"Langan","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_4","first-page":"832","article-title":"Revised Nomenclature for Allergy for Global Use","volume":"113","author":"Johansson","year":"2004","journal-title":"Rep. Nomencl. Rev. Comm. World Allergy Organ."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S0140-6736(06)69283-0","article-title":"Worldwide Time Trends in the Prevalence of Symptoms of Asthma, Allergic Rhinoconjunctivitis, and Eczema in Childhood: ISAAC Phases One and Three Repeat Multicountry Cross-Sectional Surveys","volume":"368","author":"Asher","year":"2006","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1080\/09546634.2016.1174765","article-title":"Addressing Treatment Challenges in Atopic Dermatitis with Novel Topical Therapies","volume":"27","author":"Silverberg","year":"2016","journal-title":"J. Dermatol. Treat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/j.1525-1470.2011.01493.x","article-title":"V Potential Barriers to Adherence in Pediatric Dermatology","volume":"28","author":"Ellis","year":"2011","journal-title":"Pediatr. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ferreira, K.C., Valle, A.B.S., Paes, C.Q., Tavares, G.D., and Pittella, F. (2021). Nanostructured Lipid Carriers for the Formulation of Topical Anti-Inflammatory Nanomedicines Based on Natural Substances. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13091454"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Forni, C., Facchiano, F., Bartoli, M., Pieretti, S., Facchiano, A., D\u2019Arcangelo, D., Norelli, S., Valle, G., Nisini, R., and Beninati, S. (2019). Beneficial Role of Phytochemicals on Oxidative Stress and Age-Related Diseases. BioMed Res. Int., 2019.","DOI":"10.1155\/2019\/8748253"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1111\/1523-1747.ep12338475","article-title":"Analysis of Familial Aggregation of Atopic Eczema and Other Atopic Diseases by Odds Ratio Regression Models","volume":"106","author":"Diepgen","year":"1996","journal-title":"J. Investig. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.anai.2019.10.008","article-title":"The Role of Filaggrin in Atopic Dermatitis and Allergic Disease","volume":"124","author":"Drislane","year":"2019","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1007\/BF02505232","article-title":"Decreased Expression of Filaggrin in Atopic Skin","volume":"288","author":"Seguchi","year":"1996","journal-title":"Arch. Dermatol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.jaci.2016.06.010","article-title":"Cellular and Molecular Immunologic Mechanisms in Patients with Atopic Dermatitis","volume":"138","author":"Werfel","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1172\/JCI21060","article-title":"New Insights into Atopic Dermatitis","volume":"113","author":"Leung","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"R7","DOI":"10.1016\/j.jaci.2009.07.012","article-title":"Cytokine Modulation of Atopic Dermatitis Filaggrin Skin Expression","volume":"124","author":"Howell","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1016\/j.jaci.2017.04.004","article-title":"Novel Concepts of Prevention and Treatment of Atopic Dermatitis through Barrier and Immune Manipulations with Implications for the Atopic March","volume":"139","author":"Czarnowicki","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cell.2013.08.057","article-title":"The Epithelial Cell-Derived Atopic Dermatitis Cytokine TSLP Activates Neurons to Induce Itch","volume":"155","author":"Wilson","year":"2013","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.immuni.2014.01.011","article-title":"Group 2 Innate Lymphoid Cells Are Critical for the Initiation of Adaptive T Helper 2 Cell-Mediated Allergic Lung Inflammation","volume":"40","author":"Halim","year":"2014","journal-title":"Immunity"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1046\/j.1523-1747.2000.00072.x","article-title":"High-Expression of Sphingomyelin Deacylase Is an Important Determinant of Ceramide Deficiency Leading to Barrier Disruption in Atopic Dermatitis1","volume":"115","author":"Hara","year":"2000","journal-title":"J. Investig. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100256","DOI":"10.1016\/j.phyplu.2022.100256","article-title":"Curative Potency of Medicinal Plants in Management of Eczema: A Conservative Approach","volume":"2","author":"Arora","year":"2022","journal-title":"Phytomedicine Plus"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1067\/mai.2002.121702","article-title":"Staphylococcal Exotoxins Exert Proinflammatory Effects through Inhibition of Eosinophil Apoptosis, Increased Surface Antigen Expression (CD11b, CD45, CD54, and CD69), and Enhanced Cytokine-Activated Oxidative Burst, Thereby Triggering Allergic Inflammatory Reactions","volume":"109","author":"Wedi","year":"2002","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S118","DOI":"10.1016\/j.jaci.2003.09.033","article-title":"Atopic Dermatitis and the Atopic March","volume":"112","author":"Spergel","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1111\/jdv.16892","article-title":"ETFAD\/EADV Eczema Task Force 2020 Position Paper on Diagnosis and Treatment of Atopic Dermatitis in Adults and Children","volume":"34","author":"Wollenberg","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_24","first-page":"354250","article-title":"Atopic Dermatitis: Natural History, Diagnosis, and Treatment","volume":"2014","author":"Thomsen","year":"2014","journal-title":"ISRN"},{"key":"ref_25","unstructured":"Hartini, H., Vlorensia, H.A., Martinus, A.R., and Ikhtiari, R. (August, January 29). The Effect of a Moisturizing Cream Containing Saccharide Isomerate and Ceramide on Reducing Transepidermal Water Loss in Eczema. Proceedings of the International Conference on Health Informatics and Medical Application Technology, Las Vegas, NV, USA."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Nawrot, J., Budzianowski, J., Nowak, G., Micek, I., Budzianowska, A., and Gornowicz-Porowska, J. (2021). Biologically Active Compounds in Stizolophus Balsamita Inflorescences: Isolation, Phytochemical Characterization and Effects on the Skin Biophysical Parameters. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094428"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jaad.2014.03.023","article-title":"Guidelines of Care for the Management of Atopic Dermatitis: Section 2. Management and Treatment of Atopic Dermatitis with Topical Therapies","volume":"71","author":"Eichenfield","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_28","first-page":"47","article-title":"Topical Corticosteroids: Mechanisms of Action","volume":"151","author":"Kragballe","year":"1998","journal-title":"Acta Derm. Venereologica. Suppl."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1111\/jdv.17272","article-title":"Topical Therapy of Atopic Dermatitis with a Focus on Pimecrolimus","volume":"35","author":"Luger","year":"2021","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s40257-021-00629-0","article-title":"Appraisal of Proactive Topical Therapy in Atopic Dermatitis: Pros and Cons","volume":"22","author":"Thyssen","year":"2021","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s40272-013-0013-9","article-title":"Topical Calcineurin Inhibitors for Atopic Dermatitis: Review and Treatment Recommendations","volume":"15","author":"Carr","year":"2013","journal-title":"Pediatr. Drugs"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2165\/00128071-200506020-00001","article-title":"Safety and Efficacy of Topical Calcineurin Inhibitors in the Treatment of Childhood Atopic Dermatitis","volume":"6","author":"Breuer","year":"2005","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s40257-013-0020-1","article-title":"Topical Calcineurin Inhibitors and Lymphoma Risk: Evidence Update with Implications for Daily Practice","volume":"14","author":"Siegfried","year":"2013","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"185","DOI":"10.2165\/00002018-200831030-00001","article-title":"The US FDA \u2018Black Box\u2019 Warning for Topical Calcineurin Inhibitors","volume":"31","author":"Ring","year":"2008","journal-title":"Drug Saf."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.jaad.2017.06.010","article-title":"Long-Term Safety of Crisaborole Ointment 2% in Children and Adults with Mild to Moderate Atopic Dermatitis","volume":"77","author":"Eichenfield","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3000605231169445","DOI":"10.1177\/03000605231169445","article-title":"Difamilast for the Treatment of Atopic Dermatitis","volume":"51","author":"Freitas","year":"2023","journal-title":"J. Int. Med. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/bjd.21037","article-title":"The Pan-JAK Inhibitor Delgocitinib in a Cream Formulation Demonstrates Dose Response in Chronic Hand Eczema in a 16-Week Randomized Phase IIb Trial","volume":"187","author":"Worm","year":"2022","journal-title":"Br. J. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/sj.jid.5701011","article-title":"Characterization of a Hapten-Induced, Murine Model with Multiple Features of Atopic Dermatitis: Structural, Immunologic, and Biochemical Changes Following Single Versus Multiple Oxazolone Challenges","volume":"128","author":"Man","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jaci.2018.11.014","article-title":"Insights into Atopic Dermatitis Gained from Genetically Defined Mouse Models","volume":"143","author":"Nakajima","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/jid.2008.106","article-title":"Animal Models of Atopic Dermatitis","volume":"129","author":"Jin","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jep.2017.12.022","article-title":"Ameliorative Effects of Juniperus Rigida Fruit on Oxazolone- and 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice","volume":"214","author":"Lee","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_42","first-page":"4710","article-title":"Effect Of Vitisvinifera Extract And Polyphenolicfraction In Treatment Of Induced Atopic Dermatitis Inmice","volume":"8","author":"Aziz","year":"2021","journal-title":"NVEO\u2014Nat. Volatiles Essent. Oils J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"153679","DOI":"10.1016\/j.phymed.2021.153679","article-title":"Topical Treatment with Mastic (Resin from Pistacia Lentiscus) Elicits Anti-Inflammatory and Anti-Pruritic Responses by Modulating Keratinocyte Activation in a Mouse Model of Allergic Dermatitis","volume":"91","author":"Kishimoto","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.2174\/0929867323666160627110342","article-title":"Mechanism of Action of Flavonoids in Prevention of Inflammation- Associated Skin Cancer","volume":"23","author":"George","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"153691","DOI":"10.1016\/j.phymed.2021.153691","article-title":"Effects of Topical Application of a Tri-Herb Formula on Inflammatory Dry-Skin Condition in Mice with Oxazolone-Induced Atopic Dermatitis","volume":"91","author":"Wu","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e2854238","DOI":"10.1155\/2021\/2854238","article-title":"The Suppressive Effect of Mamiran Cream on Atopic Dermatitis-Like Skin Lesions In Vivo","volume":"2021","author":"Aierken","year":"2021","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_47","first-page":"97","article-title":"Mast Cells and Pro-Inflammatory Cytokines Roles in Assessment of Grape Seeds Extract Anti-Inflammatory Activity in Rat Model of Carrageenan-Induced Paw Edema","volume":"21","author":"Mohamed","year":"2018","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"153708","DOI":"10.1016\/j.phymed.2021.153708","article-title":"Improves DNCB-Induced Atopic Dermatitis in Mice and Regulated TNF-Alpa\/IFN-Gamma-Induced Skin Inflammatory Responses in HaCaT Cells","volume":"91","author":"Hwang","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Kim, T.-Y., Park, N.-J., Jegal, H., Paik, J.-H., Choi, S., Kim, S.-N., and Yang, M.H. (2023). Nymphoides Peltata Root Extracts Improve Atopic Dermatitis by Regulating Skin Inflammatory and Anti-Oxidative Enzymes in 2,4-Dinitrochlorobenzene (DNCB)-Induced SKH-1 Hairless Mice. Antioxidants, 12.","DOI":"10.3390\/antiox12040873"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s13580-021-00393-4","article-title":"Essential Oil from Chrysanthemum Boreale Flowers Modulates SNARE Protein-Linked Mast Cell Response and Skin Barrier Proteins and Ameliorates Atopic Dermatitis-like Lesions in Mice","volume":"63","author":"Kim","year":"2022","journal-title":"Hortic. Environ. Biotechnol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1080\/15287394.2021.1955785","article-title":"Topical Application of Celastrol Alleviates Atopic Dermatitis Symptoms Mediated through the Regulation of Thymic Stromal Lymphopoietin and Group 2 Innate Lymphoid Cells","volume":"84","author":"Lee","year":"2021","journal-title":"J. Toxicol. Environ. Health Part A"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"827","DOI":"10.3892\/mmr.2021.12467","article-title":"Lycopus lucidus Turcz ameliorates DNCB-induced atopic dermatitis in BALB\/c mice","volume":"24","author":"Min","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"114474","DOI":"10.1016\/j.jep.2021.114474","article-title":"Anti-Atopic Effect of Viola Yedoensis Ethanol Extract against 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-like Skin Dysfunction","volume":"280","author":"Fan","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"153418","DOI":"10.1016\/j.phymed.2020.153418","article-title":"Diosmin Restores the Skin Barrier by Targeting the Aryl Hydrocarbon Receptor in Atopic Dermatitis","volume":"81","author":"Lee","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s40816-021-00306-z","article-title":"Impact of Althaea Officinalis Extract in Patients with Atopic Eczema: A Double-Blind Randomized Controlled Trial","volume":"7","author":"Khalighi","year":"2021","journal-title":"Clin. Phytoscience."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1002\/ptr.6899","article-title":"Effect of Topical Marshmallow (Althaea Officinalis) on Atopic Dermatitis in Children: A Pilot Double-Blind Active-Controlled Clinical Trial of an in-Silico-Analyzed Phytomedicine","volume":"35","author":"Naseri","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"112477","DOI":"10.1016\/j.jep.2019.112477","article-title":"Efficacy and Safety of Indigo Naturalis Ointment in Treating Atopic Dermatitis: A Randomized Clinical Trial","volume":"250","author":"Lin","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jdermsci.2009.02.007","article-title":"Anti-Psoriatic Effects of Indigo Naturalis on the Proliferation and Differentiation of Keratinocytes with Indirubin as the Active Component","volume":"54","author":"Lin","year":"2009","journal-title":"J. Dermatol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.jep.2012.11.044","article-title":"Indigo Naturalis Upregulates Claudin-1 Expression in Human Keratinocytes and Psoriatic Lesions","volume":"145","author":"Lin","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.2174\/1871530320666201023125411","article-title":"Efficacy of Short Term Topical Malva Sylvestris L. Cream in Pediatric Patients with Atopic Dermatitis: A Randomized Double-Blind Placebo-Controlled Clinical Trial","volume":"21","author":"Meysami","year":"2021","journal-title":"Endocrine Metab. Immune Disord. Drug Targets"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3831\/KPI.2020.23.3.173","article-title":"Comparing the Therapeutic Effects of Aloe Vera and Olive Oil Combination Cream versus Topical Betamethasone for Atopic Dermatitis: A Randomized Double-Blind Clinical Trial","volume":"23","author":"Panahi","year":"2020","journal-title":"J. Pharmacopunct."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1089\/acm.2020.0343","article-title":"A Comparison of the Effect of Topical Preparation of Sambucus Ebulus L. and Hydrocortisone on Hand Eczema: A Double-Blind Randomized Controlled Trial","volume":"27","author":"Farahani","year":"2021","journal-title":"J. Altern. Complement. Med."},{"key":"ref_63","first-page":"2399","article-title":"Ursolic Acid Inhibits Cyclooxygenase-2 Transcription in Human Mammary Epithelial Cells","volume":"60","author":"Subbaramaiah","year":"2000","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1007\/BF02972975","article-title":"Inhibitory Effect on TNF-Alpha-Induced IL-8 Production in the HT29 Cell of Constituents from the Leaf and Stem of Weigela Subsessilis","volume":"28","author":"Thuong","year":"2005","journal-title":"Arch. Pharmacal Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.jep.2010.10.049","article-title":"Identification and Pharmacological Characterization of the Anti-Inflammatory Principal of the Leaves of Dwarf Elder (Sambucus Ebulus L.)","volume":"133","author":"Schwaiger","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.explore.2023.10.005","article-title":"Efficacy and Safety of Purslane (Portulaca Oleracea) for Mild to Moderate Chronic Hand Eczema; A Randomized, Double-Blind, Placebo-Controlled Clinical Trial","volume":"20","author":"Heydarirad","year":"2023","journal-title":"Explore"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"986943","DOI":"10.3389\/fnut.2022.986943","article-title":"Portulaca Oleracea L. Extracts Alleviate 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice","volume":"9","author":"Lv","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s43014-023-00138-z","article-title":"A Review on Biochemical Constituents of Pumpkin and Their Role as Pharma Foods; a Key Strategy to Improve Health in Post COVID 19 Period","volume":"5","author":"Hussain","year":"2023","journal-title":"Food Prod. Process. Nutr."},{"key":"ref_69","first-page":"1339","article-title":"Efficacy of Pumpkin Ointment in Treatment of Chronic Hand Eczema: A Randomized, Active-Controlled, Double Blind Clinical Trial","volume":"49","author":"Khademi","year":"2020","journal-title":"Iran. J. Public Health"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"20940","DOI":"10.1038\/s41598-020-77039-5","article-title":"Eucalyptus Oil Reduces Allergic Reactions and Suppresses Mast Cell Degranulation by Downregulating IgE-Fc\u03b5RI Signalling","volume":"10","author":"Nakamura","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Lee, S., Jegal, H., Bong, S.-K., Yoon, K.-N., Park, N.-J., Shin, M.-S., Yang, M.H., Kim, Y.K., and Kim, S.-N. (2019). Anti-Atopic Effect of Acorn Shell Extract on Atopic Dermatitis-Like Lesions in Mice and Its Active Phytochemicals. Biomolecules, 10.","DOI":"10.3390\/biom10010057"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Wu, S., Yu, D., Liu, W., Zhang, J., Liu, X., Wang, J., Yu, M., Li, Z., Chen, Q., and Li, X. (2020). Magnoflorine from Coptis Chinese Has the Potential to Treat DNCB-Induced Atopic Dermatits by Inhibiting Apoptosis of Keratinocyte. Bioorganic Med. Chem., 28.","DOI":"10.1016\/j.bmc.2019.115093"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Yang, K., Kim, S.-Y., Park, J.-H., Ahn, W.-G., Jung, S.H., Oh, D., Park, H.C., and Choi, C. (2020). Topical Application of Phlorotannins from Brown Seaweed Mitigates Radiation Dermatitis in a Mouse Model. Mar. Drugs, 18.","DOI":"10.3390\/md18080377"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"114453","DOI":"10.1016\/j.jep.2021.114453","article-title":"Effects of Chloroform Fraction of Fritillariae Thunbergii Bulbus on Atopic Symptoms in a DNCB-Induced Atopic Dermatitis-like Skin Lesion Model and in Vitro Models","volume":"281","author":"Kim","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_75","first-page":"155","article-title":"Effect of Herbal Cream Containing Fumaria Officinalis and Silymarin for Treatment of Eczema: A Randomized Double-Blind Controlled Clinical Trial","volume":"12","author":"Iraji","year":"2022","journal-title":"Avicenna J. Phytomed."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Lohan, S.B., Saeidpour, S., Colombo, M., Staufenbiel, S., Unbehauen, M., Wolde-Kidan, A., Netz, R.R., Bodmeier, R., Haag, R., and Teutloff, C. (2020). Nanocrystals for Improved Drug Delivery of Dexamethasone in Skin Investigated by EPR Spectroscopy. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12050400"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Tadi\u0107, V.M., \u017dugi\u0107, A., Martinovi\u0107, M., Stankovi\u0107, M., Maksimovi\u0107, S., Frank, A., and Ne\u0161i\u0107, I. (2021). Enhanced Skin Performance of Emulgel vs. Cream as Systems for Topical Delivery of Herbal Actives (Immortelle Extract and Hemp Oil. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13111919"},{"key":"ref_78","first-page":"380","article-title":"Nanotechnology Meets Atopic Dermatitis: Current Solutions, Challenges and Future Prospects. Insights and Implications from a Systematic Review of the Literature","volume":"4","author":"Damiani","year":"2019","journal-title":"Bioact. Mater."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2100002","DOI":"10.1002\/ejlt.202100002","article-title":"Development of Phospholipids Vesicular Nanocarrier for Topical Delivery of Tea Tree Oil in Management of Atopic Dermatitis Using BALB\/c Mice Model","volume":"123","author":"Kumar","year":"2021","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7666","DOI":"10.1021\/acsabm.0c00854","article-title":"Nano- and Microfiber PVB Patches as Natural Oil Carriers for Atopic Skin Treatment","volume":"3","author":"Krysiak","year":"2020","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"105256","DOI":"10.1016\/j.ejps.2020.105256","article-title":"Nano-Elastic Liposomes as Multidrug Carrier of Sodium Stibogluconate and Ketoconazole: A Potential New Approach for the Topical Treatment of Cutaneous Leishmaniasis","volume":"145","author":"Dar","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"892","DOI":"10.2174\/2210681210666200210115526","article-title":"Formulation and Evaluation of DHA Oil Based Nicotinamide Nanoemulsion Gel for Treating Atopic Dermatitis","volume":"10","author":"Pradeep","year":"2020","journal-title":"Nanosci. Nanotechnol. -Asia"},{"key":"ref_83","first-page":"265","article-title":"Effect of Zeta Potential on the Properties of Nano-Drug Delivery Systems\u2014A Review (Part 2)","volume":"12","author":"Honary","year":"2013","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.jmii.2014.07.006","article-title":"Tacrolimus Suppresses Atopic Dermatitis-Associated Cytokines and Chemokines in Monocytes","volume":"49","author":"Chang","year":"2016","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Khan, A.S., Shah, K.U., Mohaini, M.A., Alsalman, A.J., Hawaj, M.A.A., Alhashem, Y.N., Ghazanfar, S., Khan, K.A., Niazi, Z.R., and Farid, A. (2022). Tacrolimus-Loaded Solid Lipid Nanoparticle Gel: Formulation Development and In Vitro Assessment for Topical Applications. Gels, 8.","DOI":"10.3390\/gels8020129"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"100593","DOI":"10.1016\/j.apmt.2020.100593","article-title":"A Novel Composite of Micelles and Hydrogel for Improving Skin Delivery of Hydrocortisone and Application in Atopic Dermatitis Therapy","volume":"19","author":"Yuan","year":"2020","journal-title":"Appl. Mater. Today"},{"key":"ref_87","first-page":"E77","article-title":"English Version of Guidelines for the Management of Asteatosis 2021 in Japan","volume":"49","author":"Saeki","year":"2021","journal-title":"J. Dermatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/1346-8138.16160","article-title":"Clinical Study on the Effects of the Applied Volume of Moisturizer in Patients with Asteatosis","volume":"49","author":"Tsunemi","year":"2022","journal-title":"J. Dermatol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1159\/000534136","article-title":"The Skin Barrier and Moisturization: Function, Disruption, and Mechanisms of Repair","volume":"36","author":"Rajkumar","year":"2023","journal-title":"Skin Pharmacol. Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Vanessa, V.V., Wan Ahmad Kammal, W.S.L., Lai, Z.W., and How, K.N. (2022). A Review of Moisturizing Additives for Atopic Dermatitis. Cosmetics, 9.","DOI":"10.3390\/cosmetics9040075"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Takagi, Y. (2024). Efficacy of Topical Application of a Skin Moisturizer Containing Pseudo-Ceramide and a Eucalyptus Leaf Extract on Atopic Dermatitis: A Review. J. Clin. Med., 13.","DOI":"10.3390\/jcm13061749"},{"key":"ref_92","first-page":"e93","article-title":"A Therapeutic Effect of Cbd-Enriched Ointment in Inflammatory Skin Diseases and Cutaneous Scars","volume":"170","author":"Palmieri","year":"2019","journal-title":"Clin. Ter."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1111\/j.1468-3083.2010.03845.x","article-title":"Comparative Trial of Moisturizer Containing Licochalcone A vs. Hydrocortisone Lotion in the Treatment of Childhood Atopic Dermatitis: A Pilot Study","volume":"25","author":"Udompataikul","year":"2011","journal-title":"J. Eur. Acad. Dermatol. Venereol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5375\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:42:30Z","timestamp":1760107350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5375"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":93,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25105375"],"URL":"https:\/\/doi.org\/10.3390\/ijms25105375","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,15]]}}}