ReferenceID 1765

Dictamnine ameliorates chronic itch in DNFB-induced atopic dermatitis mice via inhibiting MrgprA3

Biochem Pharmacol

Chronic itch is the most prominent feature of atopic dermatitis (AD), and antihistamine treatment is often less effective in reducing clinical pruritus severity in AD. Multiple studies have shown that histamine-independe

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Reference Id
1765
Evidence Id
18355
Core Evidence Id
18355
Source Reference Id
3512
Herb2 Reference Id
HBREF004309
Subject Paper Key
HBIN023700_36493846
Pubmed Id
36493846
Doi
10.1016/j.bcp.2022.115368
Paper Title
Dictamnine ameliorates chronic itch in DNFB-induced atopic dermatitis mice via inhibiting MrgprA3
Paper Abstract
Chronic itch is the most prominent feature of atopic dermatitis (AD), and antihistamine treatment is often less effective in reducing clinical pruritus severity in AD. Multiple studies have shown that histamine-independent itch pathway is thought to predominate in AD-induced chronic itch. Mas-related G-protein-coupled receptor (Mrgpr) A3 + sensory neurons have been identified as one of the major itch-sensing neuron populations, and transient receptor potential (TRP) channel A1 is the key downstream of MrgprA3-mediated histamine-independent itch. MrgprA3-TRPA1 signal pathway is necessary for the development of chronic itch and may be the potentially promising target of chronic itch in AD. Dictamnine is one of the main quinoline alkaloid components of Cortex Dictamni (a traditional Chinese medicine widely used in clinical treatment of skin diseases). However, the anti-inflammatory and anti-pruritic effect of dictamnine on AD have not been reported. In this study, we used the 2,4-dinitrofluorobenzene (DNFB)-induced AD mouse model to observe the scratching behavior, inflammatory manifestations, and to detect the expression of MrgprA3 and TRPA1 in skin and DRG. The data demonstrated that dictamnine effectively inhibited AD-induced chronic itch, inflammation symptoms, epidermal thickening, inflammatory cell infiltration, and downregulated the expression of MrgprA3 and TRPA1. Furthermore, dictamnine restrained the excitability of MrgprA3 + and TRPA1 + neurons. Molecular docking also indicated that dictamnine has better binding affinity with MrgprA3. These results suggest that dictamnine may inhibit chronic itch caused by AD through the MrgprA3-TRPA1 mediated histamine-independent itch pathway, and may have a potential utility in AD treatment.
Journal
Biochem Pharmacol
Publish Year
2022
Experiment Subject
mouse
Experiment Type
Animal Experiment
Phenotype Related
Chronic Itch; Skin Diseases; Atopic Dermatitis; Pruritus; Epidermal Thickening; Inflammation Symptoms
Paper Title Cn
Paper Title En
Dictamnine ameliorates chronic itch in DNFB-induced atopic dermatitis mice via inhibiting MrgprA3
Bilingual Status
semi_complete