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Baicalein ameliorates chronic itch in ACD mice by suppressing the spinal astrocytic STAT3-LCN2 cascade.
Du, Li-Xia; Gao, Xin-Yi; Ren, Xue-Qi; Yang, Ya-Yue; Ding, Yang-Yang; Xu, Ao; Wang, Xiao-Yu; Zhang, Yu-Xin; Shu, Shi; Yang, Yu-Fang; Mi, Wen-Li; Wang, Zhi-Fei.
Afiliación
  • Du LX; Department of Biochemistry, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Gao XY; School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Ren XQ; School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Yang YY; 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 Bra
  • Ding YY; School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Xu A; School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Wang XY; School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Zhang YX; 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 Bra
  • Shu S; School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Yang YF; School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Mi WL; 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 Bra
  • Wang ZF; School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. zfwang@shutcm.edu.cn.
Acta Pharmacol Sin ; 2024 Sep 16.
Article en En | MEDLINE | ID: mdl-39284878
ABSTRACT
Chronic itch is a maladaptive and debilitating symptom in patients with allergic contact dermatitis (ACD), adversely affecting their quality of life. There is a lack of effective treatments for ACD-associated uncontrollable itch. In this study, we explored the antipruritic effects of baicalein (BE), a bioactive flavonoid extracted from the root of Scutellaria baicalensis Georgi, and the underlying mechanisms in alleviating chronic itch triggered by diphenylcyclopropenone (DCP) in a mouse model of ACD. The ACD mice were intraperitoneally injected with BE (5, 30, and 60 mg·kg-1·d-1) for 7 days during the DCP challenge phase. The results showed that DCP-treated mice exhibited severe spontaneous scratching behaviors that was reduced after BE injections in a dose-dependent manner accompanied by inhibition of spinal astrocyte activation. We observed that the spinal astrocytic STAT3-LCN2 cascade plays a crucial role in controlling the activation of astrocytes in chronic itch. Intrathecal injection of the STAT3 inhibitor AG490 or Lcn2 siRNA significantly reduced scratching behavior and astrocyte activation in ACD mice. Moreover, BE markedly attenuated the increased phosphorylation of STAT3 (p-STAT3) and LCN2 expression in the spinal cords of ACD mice and in lipopolysaccharide-stimulated primary spinal astrocytes. Altogether, BE relieved chronic itch by suppressing the spinal astrocytic STAT3-LCN2 cascade. These findings provide a potential avenue for the management of chronic itch. Schematic summary of the main findings illustrating that BE alleviates chronic itch through suppressing the spinal astrocytic STAT3-LCN2 cascade. Specifically, BE suppresses the expression of p-STAT3 to inhibit the reactive state of astrocytes in spinal dorsal horn, and then decreases the expression of astrocytic LCN2 to alleviate chronic itch in ACD mice.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Acta Pharmacol Sin Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Acta Pharmacol Sin Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos