Abstract: 【Abstract】 Objective To investigate the effects of topical berberine ointment on skin inflammation and microbial changes in an atopic dermatitis-like mouse model. Methods Thirty-six male BALB/c mice were randomly divided into 6 groups: a blank control group, a model group, 0.01%, 0.1%, and 1% berberine groups, and a 0.03% tacrolimus group. Except for the blank control group, all mice were sensitized with 2,4-dinitrochlorobenzene on the dorsal ears; sensitization was performed three times per week during the first week （on days 1, 3, and 5）, followed by once every three days during weeks 2 and 3; from the second week onward, topical treatments were administered daily according to group assignment for two consecutive weeks. Twenty-four hours after the final treatment, skin lesions in mice were grossly evaluated. The mice were then sacrificed, and ear tissues were collected for hematoxylin and eosin staining to measure ear thickness, as well as for microbial 16S rRNA sequencing analysis. Statistical analysis was performed using one-way analysis of variance followed by the Games-Howell test. Results Ear thickness was significantly lower in all the berberine groups and the 0.03% tacrolimus group than in the model group （all P < 0.05）. Compared with the model group, the 1% berberine group showed lower Shannon indices （0.70 ± 0.41 vs. 1.31 ± 0.10, P = 0.005） and higher Simpson indices （0.64 ± 0.24 vs. 0.35 ± 0.06, P = 0.015）. The relative abundance of Staphylococcus spp. was significantly lower in the 0.1% berberine group （16.68%） than in the model group （47.23%, P < 0.001）. Conclusion In the atopic dermatitis-like mouse model, berberine ointment could reduce ear thickening, alleviate erythema and scaling, modulate the abundance of skin microbiota, and inhibit Staphylococcus spp., which provides theoretical support for its clinical application.

Key words: Dermatitis, atopic, Berberine, Therapy, Inflammation, Skin microbiota, Staphylococcus