School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, 430074, China.
Qinghai Tibetan Medicine Research Institute, Qinghai Province Key Laboratory of Tibetan Medicine Research and Development, Xining, 810016, China.
J Ethnopharmacol. 2024 Nov 15;334:118580. doi: 10.1016/j.jep.2024.118580. Epub 2024 Jul 15.
The leaves of Artemisia argyi Levl.et Vant. have a long history of being used to treat skin diseases such as pruritus and dermatitis in China, but the therapeutic effect on allergic contact dermatitis (ACD) is still unclear.
To investigate the effect and molecular mechanisms of the volatile oil of A. argyi leaves (abbreviated as 'AO') in the treatment of ACD.
The main components in AO were analyzed using GC-MS. The effect of AO on channel currents in hTRPA1-transfected HEK293T cells was studied by whole-cell patch clamp. Subsequently, chloroquine-evoked acute itch and squaraine dibutyl ester (SADBE)-induced ACD chronic itch model was established to evaluate the antipruritic effect through counting scratching behavior, and the anti-inflammatory effects on ACD mice were measured using histological analysis. Meanwhile, the changes of CGRP, the infiltration of nerve fibers and the recruitment of dendritic cells, the expression of Il-23 and Il-17 mRNA in skin lesions, the phosphorylation of ERK and p38 in dorsal root ganglion (DRG), were evaluated by molecular biological methods. Then the inhibitory effect of AO on AITC- or SADBE-activated TRPA1 channels in primary DRG neurons of C57BL/6, Trpa1 or Trpv1 mice was elucidated by Ca imaging and immunofluorescence.
AO treatment inhibited the activation of TRPA1 in HEK293T cells and alleviated acute itch caused by chloroquine, but this effect was lacking in Trpa1 mice. Furthermore, administration of AO attenuated scratching behavior in SADBE-induced ACD mice. AO also inhibited the increase of nerve fibers and recruitment of dendritic cells, and down-regulated the expression of CGRP and the levels of Il-23 and Il-17 mRNA. Meanwhile, AO reduced the expression of p-p38 and p-ERK in the lesioned skin and DRG of SADBE-induced ACD mice. Additionally, AO blocked the activation of TRPA1 channels and decreased the levels of CGRP, p-p38, and p-ERK in DRG neurons.
AO could inhibit TRPA1 channels in sensory neurons, thereby reducing the release of CGRP and exerting anti-pruritic and anti-inflammatory effect. These findings also provide a new strategy for exploring the role of A. argyi in treating ACD.
艾蒿叶在中国有悠久的历史，用于治疗瘙痒症和皮炎等皮肤病，但对过敏性接触性皮炎（ACD）的治疗效果仍不清楚。
研究艾蒿叶挥发油（简称“AO”）治疗 ACD 的作用及分子机制。
采用 GC-MS 分析 AO 的主要成分。采用全细胞膜片钳技术研究 AO 对 hTRPA1 转染 HEK293T 细胞通道电流的影响。随后，建立氯喹诱发的急性瘙痒和 squaraine 二丁酯（SADBE）诱导的 ACD 慢性瘙痒模型，通过计数搔抓行为来评估止痒作用，并通过组织学分析测量 ACD 小鼠的抗炎作用。同时，采用分子生物学方法评价皮肤病变中 CGRP、神经纤维浸润和树突状细胞募集、Il-23 和 Il-17 mRNA 的表达、背根神经节（DRG）中 ERK 和 p38 的磷酸化。然后，通过钙成像和免疫荧光法阐明 AO 对 C57BL/6、Trpa1 或 Trpv1 小鼠原代 DRG 神经元中 AITC 或 SADBE 激活的 TRPA1 通道的抑制作用。
AO 处理抑制了 HEK293T 细胞中 TRPA1 的激活，并减轻了氯喹引起的急性瘙痒，但在 Trpa1 小鼠中没有这种作用。此外，AO 给药减轻了 SADBE 诱导的 ACD 小鼠的搔抓行为。AO 还抑制了神经纤维的增加和树突状细胞的募集，并下调了 CGRP 和 Il-23 和 Il-17 mRNA 的表达。同时，AO 降低了 SADBE 诱导的 ACD 小鼠皮肤和 DRG 中 p-p38 和 p-ERK 的表达。此外，AO 阻断了感觉神经元中 TRPA1 通道的激活，并降低了 DRG 神经元中 CGRP、p-p38 和 p-ERK 的水平。
AO 可抑制感觉神经元中的 TRPA1 通道，从而减少 CGRP 的释放，并发挥止痒和抗炎作用。这些发现也为探索艾蒿在治疗 ACD 中的作用提供了新策略。
