Artemisia annua Extract Ameliorates Atopic Dermatitis: Evidence from 3D Epidermal Model and Complementary in vitro Assays

Yuanyuan Tian,1,2,* Lei Jiao,1,2,* Yiran Li,3,* Yi Tian,1,2 Yuanyuan Chen,4 Haidong Jia,4 Lin Ma1,2 1Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, People’s Republic of China; 3Bioinformatics Facility, National Infrastructure for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Shanghai Jahwa United Co., Ltd., Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Ma, Email [email protected] Haidong Jia, Email [email protected]: Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease. The disruption of the epidermal barrier and the inflammatory response are the key factors for the occurrence and development of this disease. Artemisia annua extract (AAE), a widely used traditional Chinese medicine, exhibits anti-inflammatory properties that may benefit AD management.Objective: To evaluate the ability of AAE to inhibit inflammation and promote skin barrier repair in an AD-like three-dimensional (3D) epidermal equivalent model.Methods: Keratinocytes were treated with three AAE concentrations (0.1%, 0.3%, and 1%) to assess their cytotoxic effects using Cell Counting Kit-8. Methyl-β-cyclodextrin and interleukin (IL)-4, IL-13, and IL-25 were used to induce the AD-like model. The expression of skin structural proteins, inflammatory factors, and histopathological manifestations were compared among AAE-treated AD models, an untreated AD model, and normal control models.Results: Expression of the skin barrier proteins filaggrin (p < 0.0001, 95% CI: 0.7006 to 0.8265), loricrin (p < 0.0001, 95% CI: 0.2028 to 0.3031), and desmoglein-1 (p < 0.05, 95% CI: 0.0298 to 0.4227) was remarkably restored, whereas that of HAS3 (p < 0.05, 95% CI: 1.169 to 7.207), NELL2 (p < 0.0001, 95% CI: 5.787 to 6.978), TSLP (p < 0.01, 95% CI: 1.657 to 7.513), and IL-1α (p < 0.001, 95% CI: 19.33 to 63.35), IL-6 (p < 0.01, 95% CI: 2.474 to 13.78), and IL-8 (p < 0.0001, 95% CI: 36.55 to 55.63) was reduced significantly in 1% AAE concentration. AAE may exert its effects by inhibiting the over-activation of the MAPK pathway in an AD-like 3D epidermal model.Conclusion: 1% AAE inhibits inflammation and promotes skin barrier function in an AD-like 3D epidermal equivalent model. AAE which mainly includes Arteannuin B, Chlorogenic Acid, Chrysoplenol D, Scopolin, and Vitexicarpin is identified as the putative targets for AD therapy.Keywords: atopic dermatitis, epidermal equivalent model, Artemisia annua extract, skin barrier, anti-inflammatory