Network Pharmacology Integrated with Transcriptomics Analysis Reveals Ermiao Wan Alleviates Atopic Dermatitis via Suppressing MAPK and Activating the EGFR/AKT Signaling

Ting Xia,1– 3 Xiao Liang,4 Chang-Shun Liu,1– 3 Yan-Nan Hu,1– 3 Zhen-Ye Luo,1– 3 Xiao-Mei Tan1– 3 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 3Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou, 510515, People’s Republic of China; 4School of Pharmaceutical Sciences, Guilin Medical University, Guilin, 541199, People’s Republic of ChinaCorrespondence: Xiao-Mei Tan, Tel/Fax + 86-020-61648265, Email tanxm_smu@163.comBackground: Ermiao Wan (EMW) is commonly used to treat atopic dermatitis (AD) in China. However, the pharmacological mechanisms underlying the action of EMW against AD remain unclear.Purpose: We aimed to determine the mechanisms underlying the effectiveness of EMW in the treatment of AD.Methods: We evaluated the effect of EMW on AD induced by dinitrochlorobenzene (DNCB) in BALB/C mice. To clarify the key components of EMW in AD treatment, the main components of EMW were identified using HPLC. Serum pharmacochemistry was used to analyze the absorbed ingredients from blood. Based on the phytochemical results, network pharmacology and molecular docking were used to predict the action of EMW. Skin transcriptomic analysis was used to validate the network pharmacology results. RT-qPCR,ELISA, and immunohistochemical were performed to validate the results of skin transcriptomics.Results: EMW improved the symptoms of AD, with less rashes, less spontaneous scratching, less inflammatory cell infiltration, and fewer allergic reactions. The established HPLC method is simple and reliable. Chlorogenic acid, phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, and atractylodin were the key effective ingredients with a high blood concentration. Fifty-seven primary causal targets of