Kwon, Yu jin Kang, Yoon Jin Kwon, Jaeyoung Cho, Suyeon Kim, Jiyoon Le, Tam Thi Hwang, Ho Seong Deshar, Barsha Kim, Myungjun Kim, Ju Yeong Jung, Jae Hung Kim, Hyung-Sik Jung, Sang Hoon Kwon, Hak Cheol Kim, Won Kyu 2024-01-12T06:31:36Z 2024-01-12T06:31:36Z 2023-11-21 2024-05 0105-4538 https://pubs.kist.re.kr/handle/201004/79708 Background Atopic dermatitis (AD) is a complex condition characterized by impaired epithelial barriers and dysregulated immune cells. In this study, we demonstrated Forsythia velutina Nakai extract (FVE) simultaneously inhibits basophils, macrophages, keratinocytes, and T cells that are closely interrelated in AD development. Methods We analyzed the effect of FVE on nitric oxide and reactive oxygen species (ROS) production in macrophages, basophil degranulation, T cell activation, and tight junctions in damaged keratinocytes. Expression of cell-type-specific inflammatory mediators was analyzed, and the underlying signaling pathways for anti-inflammatory effects of FVE were investigated. The anti-inflammatory effects of FVE were validated using a DNCB-induced mouse model of AD. Anti-inflammatory activity of compounds isolated from FVE was validated in each immune cell type. Results FVE downregulated the expression of inflammatory mediators and ROS production in macrophages through TLR4 and NRF2 pathways modulation. It significantly reduced basophil degranulation and expression of type 2 (T2) and pro-inflammatory cytokines by perturbing FcεRI signaling. Forsythia velutina Nakai extract also robustly inhibited the expression of T2 cytokines in activated T cells. Furthermore, FVE upregulated the expression of tight junction molecules in damaged keratinocytes and downregulated leukocyte attractants, as well as IL-33, an inducer of T2 inflammation. In the AD mouse model, FVE showed superior improvement in inflammatory cell infiltration and skin structure integrity compared to dexamethasone. Dimatairesinol, a lignan dimer, was identified as the most potent anti-inflammatory FVE compound. Conclusion Forsythia velutina Nakai extract and its constituent compounds demonstrate promising efficacy as a therapeutic option for prolonged AD treatment by independently inhibiting various cell types associated with AD and disrupting the deleterious link between them. English Blackwell Publishing Inc. Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation Article 10.1111/all.15967 1 Allergy: European Journal of Allergy and Clinical Immunology, v.79, no.5, pp.1242 - 1257 Allergy: European Journal of Allergy and Clinical Immunology 79 5 1242 1257 N scie scopus 001111636400001 Allergy Immunology Allergy Immunology Article atopic dermatitis epithelial barrier Forsythia velutina Nakai inflammation natural product