{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:59:53Z","timestamp":1790315993970,"version":"4.1.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"\n Background<\/jats:title>\n \n Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by immune dysregulation and impaired epidermal barrier function. Interleukin-22 (IL-22) contributes to epidermal inflammation and disrupts keratinocyte differentiation, whereas filaggrin is essential for maintaining epidermal barrier integrity.\n Averrhoa bilimbi<\/jats:italic>\n leaves contain phytochemical constituents with potential anti-inflammatory activity, but their effects on IL-22 and filaggrin expression in AD remain unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To evaluate the effects of topical\n A. bilimbi<\/jats:italic>\n leaf ethanolic extract cream (ABLEC) on skin-tissue IL-22 concentrations and filaggrin expression in a 2,4-dinitrofluorobenzene- and ovalbumin-induced murine model of AD.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This randomized posttest-only controlled animal study included 30 male BALB\/c mice allocated to six groups (\n n<\/jats:italic>\n \u2009=\u20095\/group): vehicle control, positive control treated with 0.1% betamethasone valerate, untreated AD control, and ABLEC at 0.01%, 0.02%, and 0.04%. AD-like inflammation was induced with dinitrofluorobenzene and ovalbumin for 28\u2005days. Assigned topical preparations were subsequently applied at 42\u2005mg to a 6-cm\n 2<\/jats:sup>\n dorsal skin area every 12\u2005h for 14\u2005days. Cutaneous IL-22 levels were measured by enzyme-linked immunosorbent assay, whereas filaggrin expression was assessed immunohistochemically and quantified using ImageJ. IL-22 data were analyzed using the Kruskal\u2013Wallis test followed by Dunn's\n post-hoc<\/jats:italic>\n test with Benjamini\u2013Hochberg false-discovery-rate correction; filaggrin expression was analyzed using one-way ANOVA.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Cutaneous IL-22 concentrations differed significantly among groups (Kruskal\u2013Wallis\u2009=\u200912.927,\n p<\/jats:italic>\n \u2009=\u20090.024;\n \u03b5<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u20090.330). The vehicle control, positive control, ABLEC 0.02%, and ABLEC 0.04% groups showed significantly lower IL-22 concentrations than the untreated AD control (adjusted\n p<\/jats:italic>\n \u2009=\u20090.024 for each). However, none of the ABLEC groups differed significantly from the vehicle control, indicating that an extract-specific effect could not be demonstrated. Filaggrin expression did not differ significantly among groups (\n p<\/jats:italic>\n \u2009=\u20090.547;\n \u03c9<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u20090.000).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n ABLEC at 0.02% and 0.04% were associated with lower cutaneous IL-22 concentrations than the untreated AD control, but similar reductions in the vehicle control precluded demonstration of an extract-specific effect. Furthermore, no statistically detectable difference in filaggrin expression or dose\u2013response relationship was observed.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmed.2026.1883375","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:32:28Z","timestamp":1790314348000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of topical Averrhoa bilimbi leaf extract cream on IL-22 and filaggrin in a murine model of atopic dermatitis"],"prefix":"10.3389","volume":"13","author":[{"given":"Cut Putri","family":"Hazlianda","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology, Faculty of Medicine, Universitas Sumatera Utara","place":["Medan, Indonesia"]},{"name":"Philosophy Doctor in Medicine Program, Faculty of Medicine, Universitas Sumatera Utara","place":["Medan, Indonesia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunita","family":"Sari Pane","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Sumatera Utara","place":["Medan, Indonesia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona Duma Sari","family":"Lubis","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Faculty of Medicine, Universitas Sumatera Utara","place":["Medan, Indonesia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrina Yunita Murni","family":"Rambe","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, Faculty of Medicine, Universitas Sumatera Utara","place":["Medan, Indonesia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khairuddin","family":"Djawad","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Faculty of Medicine, Hasanuddin University","place":["Makassar, Indonesia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidya Imelda","family":"Laksmi","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Faculty of Medicine, Universitas Sumatera Utara","place":["Medan, Indonesia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa Mahmud","family":"Amin","sequence":"additional","affiliation":[{"name":"Philosophy Doctor in Medicine Program, Faculty of Medicine, Universitas Sumatera Utara","place":["Medan, Indonesia"]},{"name":"Department of Psychiatry, Faculty of Medicine, Universitas Sumatera Utara","place":["Medan, Indonesia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"Restimulia","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, Faculty of Medicine, Universitas Sumatera 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