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Journal article
Cimifugin Relieves Histamine-Independent Itch in Atopic Dermatitis via Targeting the CQ Receptor MrgprA3
ACS omega, v 9(6), pp 7239-7248
13 Feb 2024
PMID: 38371844
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: We previously found that cimifugin has a potent antiallergic inflammatory effect in atopic dermatitis (AD). However, whether cimifugin has an antipruritic effect in AD was unknown. Methods: Mouse scratching behavior tests were performed to verify the proposed antipruritic effect of cimifugin on DNFB- or FITC-mediated AD. Chloroquine (CQ)- and compound 48/80-evoked acute itch models were employed to clarify the effect of cimifugin on histamine-dependent or -independent itch. Intracellular calcium changes were assessed in a primary culture of mouse dorsal root ganglia (DRG) in response to pruritogen exposure with or without cimifugin treatment, including CQ, histamine, allyl-isothiocyanate (AITC), and capsaicin. Molecular docking and microscale thermophoresis (MST) assays were performed to predict and verify the binding ability and modes between cimifugin and the CQ receptor MrgprA3, respectively. Results: We found that cimifugin attenuates itch behaviors effectively in FITC-induced AD. Notably, cimifugin significantly alleviated acute itching behaviors induced by CQ but not compound 48/80 in vivo. Moreover, cimifugin remarkably inhibited CQ-evoked calcium influx in DRG cells but had no obvious effect on histamine-induced calcium influx. Nevertheless, cimifugin did not interfere with either AITC-stimulated TRPA1 activation- or capsaicin-stimulated TRPV1 activation-mediated calcium influx in DRG cells. Molecular docking predicted that CQ and cimifugin might share similar binding abilities and binding modes with MrgprA3. MST assay confirmed cimifugin directly targeting MrgprA3. Conclusion: The present study demonstrates that cimifugin has a potent antipruritic effect in AD with a histamine-independent mechanism via targeting the CQ receptor MrgprA3. Thus, cimifugin is a promising candidate antipruritic agent for AD.
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Details
- Title
- Cimifugin Relieves Histamine-Independent Itch in Atopic Dermatitis via Targeting the CQ Receptor MrgprA3
- Creators
- Jie Zheng - Nanjing University of Chinese MedicineAnqi Gu - Nanjing University of Chinese MedicineLingxuan Kong - Drexel UniversityWenhan Lu - Drexel UniversityJingsheng Xia - Drexel University, Pharmacology and PhysiologyHuijuan Hu - Department of Pharmacology and Physiology, College of MedicineMin Hong - Nanjing University of Chinese Medicine
- Publication Details
- ACS omega, v 9(6), pp 7239-7248
- Publisher
- American Chemical Society
- Number of pages
- 10
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:001159017600001
- Scopus ID
- 2-s2.0-85184818798
- Other Identifier
- 991021861287604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Chemistry, Multidisciplinary