2. Academic Validation
  3. Xanthotoxol relieves itch in mice via suppressing spinal GRP/GRPR signaling

Xanthotoxol relieves itch in mice via suppressing spinal GRP/GRPR signaling

  • Eur J Pharmacol. 2023 Oct 21:176147. doi: 10.1016/j.ejphar.2023.176147.
Xinyi Gao 1,  Yayue Yang 2,  Jianyu Zhu 2,  Yuxin Zhang 2,  Chenghao Wang 2,  Zhifei Wang 3,  Wenli Mi 4,  Lixia Du 5
Affiliations

Affiliations

  • 1 School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 2 Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • 3 School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: zfwang@shutcm.edu.cn.
  • 4 Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai, 200032, China. Electronic address: wenlimi@fudan.edu.cn.
  • 5 Department of Biochemistry, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: lixia_du@shutcm.edu.cn.
PMID: 37871763 DOI: 10.1016/j.ejphar.2023.176147
Abstract

Although pruritus, commonly known as itch, is a common and debilitating symptom associated with various skin conditions, there is a lack of effective therapies available. Xanthotoxol (XAN), a biologically active linear furocoumarin, shows potential in the treatment of various neurological disorders. In this study, we discovered that administering XAN either through intraperitoneal or intrathecal injections effectively reduced scratching behavior induced by compound 48/80 or chloroquine (CQ). Importantly, XAN also substantially alleviates chronic itch in dry skin and allergic contact dermatitis (ACD) mice. Substantial progress has highlighted the crucial role of gastrin-releasing peptide (GRP)-gastrin-releasing peptide receptor (GRPR) signaling in the dorsal spinal cord in transmitting various types of itch. Our behavior tests revealed that XAN significantly alleviated scratching behaviors induced by intrathecal administration of GRP or GRPR agonist bombesin. Furthermore, XAN reduced the activation of neurons in the spinal cord caused by intrathecal administration of GRP in mice. Moreover, XAN attenuates the activation of spinal GRPR-positive neurons in itchy mice. These findings suggest that XAN mitigates itch in mice by suppressing spinal GRP/GRPR signaling, thereby establishing XAN as a promising therapeutic option for treating pruritus.

Keywords

GRP; GRPR; Itch; Spinal cord; Xanthotoxol.

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