2. Academic Validation
  3. Dictamnine ameliorates chronic itch in DNFB-induced atopic dermatitis mice via inhibiting MrgprA3

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

  • Biochem Pharmacol. 2023 Feb:208:115368. doi: 10.1016/j.bcp.2022.115368.
Niuniu Yang 1,  Haifeng Shao 2,  Jialin Deng 2,  Yan Yang 3,  Zongxiang Tang 3,  Guanyi Wu 4,  Yanqing Liu 2
Affiliations

Affiliations

  • 1 Department of Traditional Chinese and Western Medicine, Medical College, Yangzhou University, Yangzhou 225009, China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou University, Yangzhou 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou 225002, China. Electronic address: [email protected].
  • 2 Department of Traditional Chinese and Western Medicine, Medical College, Yangzhou University, Yangzhou 225009, China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou University, Yangzhou 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou 225002, China.
  • 3 School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Key Laboratory for Chinese Medicine of Prevention and Treatment in Neurological Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 4 College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning 530299, China.
PMID: 36493846 DOI: 10.1016/j.bcp.2022.115368
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.

Keywords

Atopic dermatitis; Chronic itch; Dictamnine; MrgprA3; TRPA1.

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