Ren Mengyue, Li Siman, Li Shaoqiang, Tan Zhiwei, Shi Jun
School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510000, People's Republic of China.
Guangdong Second Traditional Chinese Medicine Hospital (Guangdong Research Institute of Traditional Chinese Medicine Manufacturing Technology), Guangzhou, Guangdong, 510000, People's Republic of China.
J Inflamm Res. 2025 May 30;18:7013-7031. doi: 10.2147/JIR.S512868. eCollection 2025.
Allergic contact dermatitis (ACD) is a delayed-type inflammatory skin illness, and its incidence rate is 10-20%. Wenqing Yin (WQY) is a classic prescription commonly used to treat ACD in China and Japan, and this study aims to explore the pharmacological effect and therapeutic mechanism of WQY to treat ACD.
The pharmacological effect of WQY were investigated using a mouse model caused by 2,4-dinitrofluorobenzene, and the Th1 and Th2 cells numbers in spleen were measured. The potential active components and signal pathways of WQY to treat ACD were obtained using UPLC-MS/MS and network pharmacological analysis, the protein expression levels in relation to the MAPK and JAK/STAT1 signaling pathways were assessed, and the serum metabolites were also analyzed.
WQY alleviated pathological injuries and reduced the increase in mast cells, reduced the thickness and weight of the ears, down-regulated the IL-6, IL-1β, IFN-γ, IL-4, T-bet, and STAT1 mRNA levels, and decreased the percentages of Th1 cells in spleen mononuclear cells of ACD mice. Meanwhile, 38 ingredients in WQY-containing serum were identified by UPLCMS/MS, and 123 overlapping target genes of WQY and ACD were then obtained. The analysis of GO and KEGG pathway enrichment of the 34 core target genes out of 123 revealed that WQY may effectively treat ACD by targeting specific biological processes, such as the MAPK and JAK-STAT signaling pathway. WQY decreased the -JAK2, -STAT1, -ERK, -JNK, and -p38 expressions in the ears of ACD mice, which led to the inhibition of JAK2/STAT1 and MAPK signaling pathways in treatment of ACD.
WQY exhibited a significant anti-inflammatory role on DNFB-induced ACD mice via inhibiting the Th1 immune response and IL-4 secretion, which may be closely linked to the JAK2/STAT1 and MAPK signaling pathways inhibition.
过敏性接触性皮炎(ACD)是一种迟发型炎症性皮肤病,其发病率为10%-20%。茵陈蒿汤(WQY)是中国和日本常用于治疗ACD的经典方剂,本研究旨在探讨WQY治疗ACD的药理作用及治疗机制。
采用2,4-二硝基氟苯诱导的小鼠模型研究WQY的药理作用,并检测脾脏中Th1和Th2细胞数量。运用超高效液相色谱-串联质谱(UPLC-MS/MS)和网络药理学分析获得WQY治疗ACD的潜在活性成分和信号通路,评估与丝裂原活化蛋白激酶(MAPK)和Janus激酶/信号转导和转录激活因子1(JAK/STAT1)信号通路相关的蛋白表达水平,并分析血清代谢产物。
WQY减轻了病理损伤,减少了肥大细胞的增加,降低了耳部厚度和重量,下调了白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)、T盒转录因子(T-bet)和信号转导和转录激活因子1(STAT1)的信使核糖核酸(mRNA)水平,并降低了ACD小鼠脾脏单个核细胞中Th1细胞的百分比。同时,通过UPLC-MS/MS鉴定了含WQY血清中的38种成分,随后获得了WQY和ACD的123个重叠靶基因。对123个中34个核心靶基因的基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析表明,WQY可能通过靶向特定生物学过程有效治疗ACD,如MAPK和JAK-STAT信号通路。WQY降低了ACD小鼠耳部JAK2、STAT1、细胞外信号调节激酶(ERK)、c-Jun氨基末端激酶(JNK)和p38的表达,这导致在治疗ACD时JAK2/STAT1和MAPK信号通路受到抑制。
WQY通过抑制Th1免疫反应和IL-4分泌对二硝基氟苯诱导的ACD小鼠表现出显著的抗炎作用,这可能与抑制JAK2/STAT1和MAPK信号通路密切相关。