Department of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, China; Department of Traditional Chinese Medicine, Naval Medical University, Shanghai, China.
Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.
J Ethnopharmacol. 2022 Sep 15;295:115428. doi: 10.1016/j.jep.2022.115428. Epub 2022 May 31.
Jiu-Wei-Yong-An (JWYA) formula is a traditional Chinese medicine (TCM) prescription used to treat atopic dermatitis (AD) in the clinic. JWYA is considered to have anti-inflammatory and antipruritic properties. However, the mechanism of JWYA remains unclear.
This study aimed to investigate the effect of JWYA on an experimental mouse AD model.
Mice were sensitized with 2,4-dinitrochlorobenzene (DNCB) and intragastrically administered with JWYA for 14 days. The therapeutic effect was assessed using a grade four dermatitis score, skin moisture, thickness measurements, and a mouse behavior tests. H&E and toluidine blue staining were used to observe epidermal inflammatory thickening and mast cells in mouse skin lesions. Serum IgE levels and skin TNF-α and IL-4 levels were determined using ELISAs. The TNF-α, IL-1β, IL-4, IL-13, IL-31, IL-33, and IFN-γ mRNA expression levels in skin lesions were detected using qPCR. Network pharmacology analysis based on serum active components was performed to elucidate the mechanism, and the results were verified by Western blotting. Finally, we tested the binding affinity between the active ingredients of JWYA and JAK1 via molecular docking.
JWYA improved the skin lesions of AD mice, relieved itching and reduced skin thickening. Additionally, JWYA decreased the serum IgE level and the levels of TNF-α, IL-1β, IL-4, IL-13, IL-31, IL-33, and IFN-γ in skin. Moreover, JWYA inhibited the activation of JAK1/STAT3 and MAPK (p38, ERK, and JNK) signaling. Molecular docking showed that kaempferol, luteolin, and forsythin have high affinity for JAK1.
JWYA alleviates AD-like skin lesions and inhibited inflammation and skin itch. The effect of JWYA is attributed to blocking the JAK1/STAT3 and MAPK signaling pathways. We suggest that JWYA may be an alternative therapy for the treatment of AD.
九味永安方（JWYA）是一种中药方剂，用于临床治疗特应性皮炎（AD）。JWYA 被认为具有抗炎和止痒作用。然而，其作用机制尚不清楚。
本研究旨在探讨 JWYA 对实验性 AD 小鼠模型的影响。
使用 2,4-二硝基氯苯（DNCB）对小鼠进行致敏，并用 JWYA 灌胃治疗 14 天。采用四级皮炎评分、皮肤水分、厚度测量和小鼠行为测试评估治疗效果。使用 H&E 和甲苯胺蓝染色观察小鼠皮肤病变中的表皮炎症增厚和肥大细胞。采用 ELISA 法测定血清 IgE 水平和皮肤 TNF-α 和 IL-4 水平。采用 qPCR 检测皮肤病变中 TNF-α、IL-1β、IL-4、IL-13、IL-31、IL-33 和 IFN-γ mRNA 的表达水平。基于血清活性成分进行网络药理学分析，阐明其作用机制，并通过 Western blot 进行验证。最后，我们通过分子对接测试了 JWYA 活性成分与 JAK1 的结合亲和力。
JWYA 改善了 AD 小鼠的皮肤病变，缓解了瘙痒并减少了皮肤增厚。此外，JWYA 降低了血清 IgE 水平以及皮肤中 TNF-α、IL-1β、IL-4、IL-13、IL-31、IL-33 和 IFN-γ 的水平。此外，JWYA 抑制了 JAK1/STAT3 和 MAPK（p38、ERK 和 JNK）信号通路的激活。分子对接表明，山奈酚、木犀草素和连翘苷与 JAK1 具有高亲和力。
JWYA 缓解 AD 样皮肤病变并抑制炎症和皮肤瘙痒。JWYA 的作用机制归因于阻断 JAK1/STAT3 和 MAPK 信号通路。我们建议 JWYA 可能是治疗 AD 的一种替代疗法。
