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

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

Urology

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1242-1257
Number of pages	16
Journal	Allergy: European Journal of Allergy and Clinical Immunology
Volume	79
Issue number	5
DOIs	https://doi.org/10.1111/all.15967
Publication status	Published - 2024 May

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

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10.1111/all.15967

Cite this

Kwon, Y., Kang, Y. J., Kwon, J., Cho, S. Y., Kim, J., Le, T. T., Hwang, H., Deshar, B., Kim, M., Kim, J. Y., Jung, J. H., Kim, H. S., Jung, S. H., Kwon, H. C., & Kim, W. K. (2024). Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation. Allergy: European Journal of Allergy and Clinical Immunology, 79(5), 1242-1257. https://doi.org/10.1111/all.15967

@article{124c717651754d05b81703207915d009,

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

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",

author = "Yujin Kwon and Kang, {Yoon Jin} and Jaeyoung Kwon and Cho, {Su Yeon} and Jiyoon Kim and Le, {Tam Thi} and Hoseong Hwang and Barsha Deshar and Myungjun Kim and Kim, {Ju Yeong} and Jung, {Jae Hung} and Kim, {Hyung Sik} and Jung, {Sang Hoon} and Kwon, {Hak Cheol} and Kim, {Won Kyu}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.",

year = "2024",

month = may,

doi = "10.1111/all.15967",

language = "English",

volume = "79",

pages = "1242--1257",

journal = "Allergy: European Journal of Allergy and Clinical Immunology",

issn = "0105-4538",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "5",

}

Kwon, Y, Kang, YJ, Kwon, J, Cho, SY, Kim, J, Le, TT, Hwang, H, Deshar, B, Kim, M, Kim, JY, Jung, JH, Kim, HS, Jung, SH, Kwon, HC & Kim, WK 2024, 'Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation', Allergy: European Journal of Allergy and Clinical Immunology, vol. 79, no. 5, pp. 1242-1257. https://doi.org/10.1111/all.15967

TY - JOUR

T1 - Forsythia velutina Nakai extract

T2 - A promising therapeutic option for atopic dermatitis through multiple cell type modulation

AU - Kwon, Yujin

AU - Kang, Yoon Jin

AU - Kwon, Jaeyoung

AU - Cho, Su Yeon

AU - Kim, Jiyoon

AU - Le, Tam Thi

AU - Hwang, Hoseong

AU - Deshar, Barsha

AU - Kim, Myungjun

AU - Kim, Ju Yeong

AU - Jung, Jae Hung

AU - Kim, Hyung Sik

AU - Jung, Sang Hoon

AU - Kwon, Hak Cheol

AU - Kim, Won Kyu

PY - 2024/5

Y1 - 2024/5

N2 - 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.

AB - 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.

KW - Forsythia velutina Nakai

KW - atopic dermatitis

KW - epithelial barrier

KW - inflammation

KW - natural product

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UR - http://www.scopus.com/inward/citedby.url?scp=85178423728&partnerID=8YFLogxK

U2 - 10.1111/all.15967

DO - 10.1111/all.15967

M3 - Article

C2 - 38037751

AN - SCOPUS:85178423728

SN - 0105-4538

VL - 79

SP - 1242

EP - 1257

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

IS - 5

ER -

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

Abstract

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