Effects of topical Averrhoa bilimbi leaf extract cream on IL-22 and filaggrin in a murine model of atopic dermatitis

Abstract

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. Averrhoa bilimbi leaves contain phytochemical constituents with potential anti-inflammatory activity, but their effects on IL-22 and filaggrin expression in AD remain unclear. To evaluate the effects of topical A. bilimbi 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. This randomized posttest-only controlled animal study included 30 male BALB/c mice allocated to six groups ( n  = 5/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 days. Assigned topical preparations were subsequently applied at 42 mg to a 6-cm 2 dorsal skin area every 12 h for 14 days. 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–Wallis test followed by Dunn's post-hoc test with Benjamini–Hochberg false-discovery-rate correction; filaggrin expression was analyzed using one-way ANOVA. Cutaneous IL-22 concentrations differed significantly among groups (Kruskal–Wallis = 12.927, p  = 0.024; ε 2  = 0.330). 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 p  = 0.024 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 ( p  = 0.547; ω 2  = 0.000). 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–response relationship was observed.