Open Access

ARTICLE

Hibifolin Modulates the Activation of Mouse Bone Marrow-Derived Dendritic Cells and Attenuates Contact Dermatitis Induced by 2,4-Dinitro-1-Fluorobenzene

Ya-Yi Chen^1,2, Tzu-Ting Chen³, Ya-Hsuan Chao⁴, Wen-Ho Chuo⁵, Chieh-Shan Wu^6,7, Ruo-Han Tseng^8,*, Chieh-Chen Huang^9,*

1 Doctoral Program in Medical Biotechnology, National Chung Hsing University, Taichung, 402, Taiwan
2 Department of Stomatology, Tungs’ Taichung Metro Harbor Hospital, Taichung, 435, Taiwan
3 Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, 300, Taiwan
4 Department of Chest Medicine, Changhua Christian Hospital, Changhua, 500, Taiwan
5 Department of Pharmacy, Tajen University, Pingtung, 907, Taiwan
6 Division of Dermatology, Pingtung Veterans General Hospital, Pingtung, 900, Taiwan
7 Department of Dermatology, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan
8 Department of Hematology and Oncology, Changhua Christian Hospital, Changhua, 500, Taiwan
9 Department of Life Sciences, National Chung Hsing University, Taichung, 402, Taiwan

* Corresponding Authors: Ruo-Han Tseng. Email: ; Chieh-Chen Huang. Email:

(This article belongs to the Special Issue: Natural and Synthetic Small Molecules in the Regulation of Immune Cell Functions)

BIOCELL 2025, 49(9), 1733-1748. https://doi.org/10.32604/biocell.2025.067011

Received 23 April 2025; Accepted 21 August 2025; Issue published 25 September 2025

Abstract

Objectives: Professional antigen-presenting cells known as dendritic cells (DCs) assist as a connection between the innate and adaptive components of the immune response. DCs are attractive targets for immunomodulatory drugs because of their crucial function in triggering immunity. This study set out to examine, for the first time, how hibifolin affected mouse bone-marrow derived (BMDCs) dendritic cells, triggered by lipopolysaccharide (LPS) in vitro. Additionally, a mouse model of contact hypersensitivity (CHS) was used to assess its possible therapeutic effects in vivo. Methods: LPS was administered to BMDCs with or without hibifolin. Major Histocompatibility Complex (MHC) class II, cytokine production, and co-stimulatory molecule (CD80, CD86) expression levels were assessed. To evaluate the functional effects on T-cell activation, mixed lymphocyte responses using OVA specific T-cells were conducted. In vivo, immunoregulatory potential of hibifolin was examined using a CHS mouse model sensitized with 2,4-dinitrofluorobenzene (DNFB). Results: Hibifolin significantly reduced the expression of the proinflammatory cytokines TNF-α and IL-6, as well as the costimulatory molecules CD80, CD86, and MHC II induced by LPS, by about 40–50%. These effects were associated with reduced NF-κB and p38-MAPK pathway activity. JNK and ERK phosphorylation levels did not alter significantly. In vitro, BMDCs treated with hibifolin showed a 40%–45% down-regulated capacity to stimulate T-cell propagation and IFN-γ release. Oral hibifolin treatment in vivo modestly decreased DNFB-induced CHS responses by 30%–40%. Conclusion: Overall, our results offer new insights that by inhibiting NF-κB and p38-MAPK signaling, hibifolin decreases the expression of costimulatory molecules and cytokines, thereby limiting BMDC activation, suppressing T-cell responses, and exerting immunomodulatory effects in the CHS mouse model.

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Supplementary Material

Supplementary Material File

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