Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation

Yujin Kwon; Yoon Jin Kang; Jaeyoung Kwon; Su-Yeon Cho; Jiyoon Kim; Tam Thi Le; Hoseong Hwang; Barsha Deshar; Myungjun Kim; Ju Yeong Kim; Jae Hung Jung; Hyung-Sik Kim; Sang Hoon Jung; Hak Cheol Kwon; Won Kyu Kim

doi:10.1111/all.15967

Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation

Allergy. 2023 Dec 1. doi: 10.1111/all.15967. Online ahead of print.

Authors

Yujin Kwon^{1

2}, Yoon Jin Kang^{1

3}, Jaeyoung Kwon^{2

4}, Su-Yeon Cho^{1

2}, Jiyoon Kim⁵, Tam Thi Le¹, Hoseong Hwang^{4

6}, Barsha Deshar⁵, Myungjun Kim⁷, Ju Yeong Kim⁷, Jae Hung Jung⁸, Hyung-Sik Kim⁹, Sang Hoon Jung^{1

2}, Hak Cheol Kwon⁴, Won Kyu Kim^{1

10}

Affiliations

¹ Natural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung, Korea.
² Division of Bio-Medical Science & Technology, University of Science and Technology (UST), Daejeon, Korea.
³ Department of Marine Life Sciences, College of Life Science, Gangneung-Wonju National University, Gangneung, Korea.
⁴ Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung, Korea.
⁵ Department of Pharmacology, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea.
⁶ Department of Biology, Gangneung-Wonju National University, Gangneung, Korea.
⁷ Department of Tropical Medicine, Institute of Tropical Medicine, and Arthropods of Medical Importance Resource Bank, Yonsei University College of Medicine, Seoul, Korea.
⁸ Department of Urology, Yonsei University Wonju College of Medicine/Center of Evidence Based Medicine Institute of Convergence Science, Wonju, Korea.
⁹ Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Korea.
¹⁰ Department of Convergence Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.

PMID: 38037751
DOI: 10.1111/all.15967

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.

Keywords: Forsythia velutina Nakai; atopic dermatitis; epithelial barrier; inflammation; natural product.

Abstract

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