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萜类化合物α-红没药醇和莰烯通过作用于Cav3.2 T型钙通道来调节瘙痒。

The terpenes alpha-bisabolol and camphene modulate pruritus via an action on Cav3.2 T-type calcium channels.

作者信息

Antunes Flavia T T, Gadotti Vinicius M, Zamponi Gerald W

机构信息

Department of Clinical Neurosciences, Cumming School of Medicine, Hotchkiss Brain Institute, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, T2N 4N1, Canada.

School of Health Sciences, Postgraduate Program in Pharmaceutical Sciences, Universidade do Vale do Itajaí (UNIVALI), Itajaí, Brazil.

出版信息

Mol Brain. 2025 Mar 18;18(1):22. doi: 10.1186/s13041-025-01196-9.

Abstract

Alpha-bisabolol and camphene have demonstrated analgesic effects in inflammatory pain models by blocking Cav3.2 calcium channels. As the pain pathway overlaps with mechanisms for itch, and because Cav3.2 channels have been associated with itch in our previous work, we aimed to investigate the potential anti-itch effects of these two terpenes. Although both terpenes failed to show anti-pruritogenic properties when dissolved in aqueous PBS, when diluted in Hydroxypropyl-beta-cyclodextrin their bioactivity significantly increased. Both compounds significantly reduced scratching in the histaminergic itch model, whether administered subcutaneously or intraperitoneally. Camphene reduced itching in the non-histaminergic model regardless of the route of administration, whereas alpha-bisabolol did not alleviate chloroquine-induced itching. When tested in Cav3.2-/- mice, neither camphene nor alpha-bisabolol significantly reduced histamine-induced scratching behavior. This suggests that the anti-pruritic actions of these terpenes may involve Cav3.2 block to mitigate itch.

摘要

α-红没药醇和莰烯已通过阻断Cav3.2钙通道在炎症性疼痛模型中显示出镇痛作用。由于疼痛通路与瘙痒机制重叠,并且鉴于在我们之前的研究中Cav3.2通道已与瘙痒相关联,我们旨在研究这两种萜类化合物的潜在止痒作用。尽管这两种萜类化合物溶解于磷酸盐缓冲盐溶液(PBS)时均未显示出抗致痒特性,但当用羟丙基-β-环糊精稀释时,它们的生物活性显著增加。无论皮下给药还是腹腔注射,这两种化合物在组胺能性瘙痒模型中均能显著减少抓挠行为。无论给药途径如何,莰烯在非组胺能模型中均可减轻瘙痒,而α-红没药醇不能缓解氯喹引起的瘙痒。在Cav3.2基因敲除小鼠中进行测试时,莰烯和α-红没药醇均未显著降低组胺诱导的抓挠行为。这表明这些萜类化合物的止痒作用可能涉及通过阻断Cav3.2来减轻瘙痒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e86/11921673/88d7e44ff852/13041_2025_1196_Fig1_HTML.jpg

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