Wenqing Yin Attenuates the Allergic Contact Dermatitis Response by Inhibiting the JAK2/STAT1 and MAPK Signaling Pathways

Mengyue Ren,1,* Siman Li,1,* Shaoqiang Li,2 Zhiwei Tan,1 Jun Shi1 1School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510000, People’s Republic of China; 2Guangdong Second Traditional Chinese Medicine Hospital (Guangdong Research Institute of Traditional Chinese Medicine Manufacturing Technology), Guangzhou, Guangdong, 510000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mengyue Ren, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510000, People’s Republic of China, Email [email protected] Jun Shi, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510000, People’s Republic of China, Email [email protected]: 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.Methods: 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.Results: 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 UPLC‒MS/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 p-JAK2, p-STAT1, p-ERK, p-JNK, and p-p38 expressions in the ears of ACD mice, which led to the inhibition of JAK2/STAT1 and MAPK signaling pathways in treatment of ACD.Conclusion: 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. Keywords: allergic contact dermatitis, Wenqing Yin, network pharmacology, 2,4-dinitrofluorobenzene, JAK2/STAT1 pathway, MAPK pathway