Kishimoto Risako, Kato Narumi, Koike Mayuka, Iwashita Naoki, Takagi Yoshiichi, Fukuyama Tomoki
Laboratory of Veterinary Pharmacology, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa, Japan.
Laboratory of Veterinary Pharmacology, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa, Japan; Bioalchemis, 3-28-61 Honshuku-cho, Fuchu-shi, Tokyo, Japan.
Phytomedicine. 2021 Oct;91:153679. doi: 10.1016/j.phymed.2021.153679. Epub 2021 Jul 19.
As the number of patients with skin allergies, including atopic dermatitis, has increased rapidly, therapeutic options such as anti-IL-31 antibody and Janus kinase inhibitor have been developed recently. However, many concerns remain regarding the adverse effects and cost of these drugs; therefore, development of supplements that could support the effect of therapeutic agents is always required.
The aim of this study was to develop preventive and supportive options for skin allergies by focusing on a natural product called "Mastic".
Initially, the anti-inflammatory and anti-pruritic responses of 3% and 30% Mastic topical treatment were investigated in a mouse model of allergic contact dermatitis, generated by topical application of toluene-2,4-diisocyanate (TDI), a hapten that induces type 2 helper T cells. After itch behaviour and ear-swelling response were monitored, serum, auricular lymph nodes, and skin tissues were collected to analyse immunocyte differentiation, cytokine determination, and histological changes.
Our findings indicated that topical treatment with mastic significantly ameliorated ear swelling, itch behaviour, immunocyte infiltration, and cytokine production. Histological evaluation confirmed the occurrence of anti-inflammatory responses. The anti-inflammatory and anti-pruritic effects of topical treatment with mastic (3% and 5%) were further confirmed in a mouse model of atopic dermatitis which was generated by topical application of TDI in NC/Nga mice. Thickness of the back skin, AD score, transepidermal water loss (TEWL), and itch behaviour were measured weekly, and immunocyte differentiation, cytokine determination, and histological changes were also analysed. Mastic treatment significantly attenuated the skin thickness, AD score, TEWL, and itch behaviour. Corroborated reduction was observed in the numbers of T cells and IgE-B cells, as well as in pro-inflammatory cytokine production. The reproducibility of the effects of mastic was confirmed with 1% mastic ointment in a setting similar to the AD mouse model. In vitro evaluation of keratinocytes indicated that mastic pre-exposure induced a significant dose-dependent decrease in cytokine production.
Our findings thus demonstrate that topical treatment with mastic significantly ameliorate inflammatory and pruritic responses in a mouse model of allergic dermatitis.
随着包括特应性皮炎在内的皮肤过敏患者数量迅速增加，近年来已开发出抗白细胞介素-31抗体和Janus激酶抑制剂等治疗方法。然而，这些药物的不良反应和成本仍存在许多问题；因此，始终需要开发能够辅助治疗药物效果的补充剂。
本研究的目的是通过关注一种名为“乳香”的天然产物，开发皮肤过敏的预防和辅助治疗方法。
首先，在由甲苯-2,4-二异氰酸酯（TDI）局部应用诱导的过敏性接触性皮炎小鼠模型中，研究3%和30%乳香局部治疗的抗炎和止痒反应。TDI是一种诱导2型辅助性T细胞的半抗原。在监测瘙痒行为和耳部肿胀反应后，收集血清、耳淋巴结和皮肤组织，以分析免疫细胞分化、细胞因子测定和组织学变化。
我们的研究结果表明，乳香局部治疗可显著改善耳部肿胀、瘙痒行为、免疫细胞浸润和细胞因子产生。组织学评估证实了抗炎反应的发生。在由TDI局部应用于NC/Nga小鼠建立的特应性皮炎小鼠模型中，进一步证实了乳香（3%和5%）局部治疗的抗炎和止痒作用。每周测量背部皮肤厚度、特应性皮炎评分、经表皮水分流失（TEWL）和瘙痒行为，并分析免疫细胞分化、细胞因子测定和组织学变化。乳香治疗显著减轻了皮肤厚度、特应性皮炎评分、TEWL和瘙痒行为。在T细胞和IgE-B细胞数量以及促炎细胞因子产生方面也观察到了相应的减少。在类似于特应性皮炎小鼠模型的环境中，用1%乳香软膏证实了乳香效果的可重复性。角质形成细胞的体外评估表明，乳香预处理可显著剂量依赖性地减少细胞因子产生。
因此，我们的研究结果表明，乳香局部治疗可显著改善过敏性皮炎小鼠模型中的炎症和瘙痒反应。
