Abstract | ETHNOPHARMACOLOGICAL RELEVANCE:
Atopic dermatitis (AD) is a complex skin disease with highly heterogeneous inflammation, which ranks among the largest component of the nonfatal diseases worldwide. The medications currently used to treat AD primarily include antihistamines, vitamin D and anti-inflammatory drugs, etc. But, the usage of these drugs is usually accompanied by various side-effects. Formononetin ( FMN), a natural active ingredient of Astragalus membranaceus (Fisch.) Bunge, decreases the AD relapse rate, reduces recurring severity incidence and resists the inflammation in the initial stage of AD. However, the underlying mechanism of FMN on repressing the development of AD is still unknown. AIM OF THE STUDY: To investigate the potential mechanism of FMN on relieving the initial responses of AD and elucidate its possible therapeutic targets in vivo and in vitro. MATERIALS AND METHODS: RESULTS: We found that FMN upregulated the expression of A20 protein and mRNA in the initial stage of AD model, especially in the epithelial region of ear tissue, and inhibited the production of TSLP simultaneously. Consistently, FMN significantly upregulated A20 protein and its mRNA expression while reduced TSLP protein and its mRNA expression in vitro, and this effect could be antagonized by A20 siRNA (siA20). Moreover, compared with PPT (ERα agonist) and DPN (ERβ agonist), G1 could significantly increase the expression of A20. In addition, compared with MPP (ERα antagonist) and PHTPP (ERβ antagonist), G15 could markedly reduce the expression of A20. Furthermore, the effects of FMN on A20 were interfered by siGPER and G15 in vitro and in vivo. CONCLUSIONS: These results demonstrated that FMN attenuated AD by upregulating A20 expression via activation of GPER. This new strategy might have effective therapeutic potential for AD and other inflammatory disorders.
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Authors | Weiyuan Yuan, Yanyan Chen, Yijing Zhou, Kaifan Bao, Xuerui Yu, Yifan Xu, Yuheng Zhang, Jie Zheng, Guorong Jiang, Min Hong |
Journal | Journal of ethnopharmacology
(J Ethnopharmacol)
Vol. 266
Pg. 113397
(Feb 10 2021)
ISSN: 1872-7573 [Electronic] Ireland |
PMID | 32971159
(Publication Type: Journal Article)
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Copyright | Copyright © 2020 Elsevier B.V. All rights reserved. |
Chemical References |
- Cytokines
- Isoflavones
- Receptors, Estrogen
- Receptors, G-Protein-Coupled
- formononetin
- TNFAIP3 protein, human
- Tumor Necrosis Factor alpha-Induced Protein 3
- Tnfaip3 protein, mouse
- Thymic Stromal Lymphopoietin
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Topics |
- Animals
- Cytokines
(metabolism)
- Dermatitis, Atopic
(drug therapy, pathology)
- Disease Models, Animal
- HaCaT Cells
- Humans
- Inflammation
(drug therapy, pathology)
- Isoflavones
(pharmacology)
- Keratinocytes
(drug effects, pathology)
- Male
- Mice
- Mice, Inbred BALB C
- Receptors, Estrogen
(metabolism)
- Receptors, G-Protein-Coupled
(metabolism)
- Tumor Necrosis Factor alpha-Induced Protein 3
(genetics)
- Up-Regulation
(drug effects)
- Thymic Stromal Lymphopoietin
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