한빛사논문
- 조회520
Yujin Kwon 1,2, Yoon Jin Kang 1,3, Jaeyoung Kwon 2,4, Su-Yeon Cho 1,2, Jiyoon Kim 5, Tam Thi Le 1, Hoseong Hwang 4,6, Barsha Deshar 5, Myungjun Kim 7, Ju Yeong Kim 7, Jae Hung Jung 8, Hyung-Sik Kim 9, Sang Hoon Jung 1,2, Hak Cheol Kwon 4, Won Kyu Kim 1,10
1Natural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung, Korea.
2Division of Bio-Medical Science & Technology, University of Science and Technology (UST), Daejeon, Korea.
3Department of Marine Life Sciences, College of Life Science, Gangneung-Wonju National University, Gangneung, Korea.
4Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung, Korea.
5Department of Pharmacology, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea.
6Department of Biology, Gangneung-Wonju National University, Gangneung, Korea.
7Department of Tropical Medicine, Institute of Tropical Medicine, and Arthropods of Medical Importance Resource Bank, Yonsei University College of Medicine, Seoul, Korea.
8Department of Urology, Yonsei University Wonju College of Medicine/Center of Evidence Based Medicine Institute of Convergence Science, Wonju, Korea.
9Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Korea.
10Department of Convergence Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
Yujin Kwon, Yoon Jin Kang, and Jaeyoung Kwon contributed equally to this work.
CORRESPONDING AUTHORS : Sang Hoon Jung, Hak Cheol Kwon, Won Kyu Kim
Abstract
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.
논문정보
- Research article
- 2023년 12월 (BRIC 등록일 2023-12-06)
- 국내 연구진
- 생명과학 > 노화/암생물학
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