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.
Department of Biochemistry, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Phytomedicine. 2023 Oct;119:154969. doi: 10.1016/j.phymed.2023.154969. Epub 2023 Jul 22.
Itch (pruritus) is a common unpleasant feeling, often accompanied by the urge of scratching the skin. It is the main symptom of many systemic and skin diseases, which can seriously affect the patient's quality of life. Geraniol (GE; trans-3,7-dimethyl-2,6-octadien-1-ol) is a natural monoterpene with diverse effects, including anti-inflammatory, antioxidant, neuroprotective, anti-nociceptive, and anticancer properties. The study aims to examine the effects of GE on acute and chronic itch, and explore the underlying mechanisms.
Acute itch was investigated by using Chloroquine and compound 48/80 induced model, followed by manifestation of diphenylcyclopropenone (DCP)-induced allergic contact dermatitis and the acetone-ether-water (AEW)-induced dry skin model in mice. The scratching behavior, skin thickness, c-Fos expression, and GRPR protein expression in the spinal cord were subsequently monitored and evaluated by behavioral tests as well as pharmacological and pharmacogenetic technologies.
Dose-dependent intraperitoneal injection of GE alleviated the acute itch, induced by chloroquine and compound 48/80, as well as increased the spinal c-Fos expression. Intrathecal administration of GE suppressed the GABA receptor inhibitor bicuculline-induced itch, GRP-induced itch, and the GABAergic neuron inhibition-induced itch. Furthermore, the subeffective dose of bicuculline blocked the anti-pruritic effect of GE on the chloroquine and compound 48/80 induced acute itch. GE also attenuated DCP and AEW-induced chronic itch, as well as the increase of spinal GRPR expression in DCP mice.
GE alleviates both acute and chronic itch via modulating the spinal GABA/GRPR signaling in mice. Findings of this study reveal that GE may provide promising therapeutic options for itch management. Also, considering the pivotal role of essential oils in aromatherapy, GE has great application potential in aromatherapy for treating skin diseases, and especially the skin with severe pruritus.
瘙痒（痒）是一种常见的不愉快感觉，常伴有搔抓皮肤的冲动。它是许多系统性和皮肤疾病的主要症状，可严重影响患者的生活质量。香叶醇（GE；反式-3,7-二甲基-2,6-辛二烯-1-醇）是一种具有多种作用的天然单萜烯，包括抗炎、抗氧化、神经保护、抗伤害感受和抗癌特性。本研究旨在探讨 GE 对急性和慢性瘙痒的影响，并探讨其潜在机制。
采用氯喹和化合物 48/80 诱导模型研究急性瘙痒，然后在小鼠中观察二苯基环丙烯酮（DCP）诱导的过敏性接触性皮炎和丙酮-乙醚-水（AEW）诱导的干燥皮肤模型。通过行为测试以及药理学和遗传药理学技术，监测和评估搔抓行为、皮肤厚度、脊髓 c-Fos 表达和脊髓 GRPR 蛋白表达。
GE 腹腔注射剂量依赖性缓解氯喹和化合物 48/80 诱导的急性瘙痒，并增加脊髓 c-Fos 表达。鞘内给予 GE 抑制 GABA 受体抑制剂荷包牡丹碱诱导的瘙痒、GRP 诱导的瘙痒和 GABA 能神经元抑制诱导的瘙痒。此外，荷包牡丹碱的亚效剂量阻断了 GE 对氯喹和化合物 48/80 诱导的急性瘙痒的抗瘙痒作用。GE 还减轻了 DCP 和 AEW 诱导的慢性瘙痒，以及 DCP 小鼠脊髓 GRPR 表达的增加。
GE 通过调节小鼠脊髓 GABA/GRPR 信号通路缓解急性和慢性瘙痒。本研究结果表明，GE 可能为瘙痒管理提供有前途的治疗选择。此外，鉴于精油在芳香疗法中的重要作用，GE 在芳香疗法治疗皮肤病，特别是严重瘙痒的皮肤方面具有很大的应用潜力。
