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

网络药理学结合转录组学分析揭示二妙丸通过抑制 MAPK 和激活 EGFR/AKT 信号传导缓解特应性皮炎

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作者:Ting Xia, Xiao Liang, Chang-Shun Liu, Yan-Nan Hu, Zhen-Ye Luo, Xiao-Mei Tan

Background

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.

Conclusion

EMW could alleviate AD through activating EGFR/AKT signaling and suppressing MAPK. This study provides a theoretical basis for the clinical use of EMW.

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

Purpose

We aimed to determine the mechanisms underlying the effectiveness of EMW in the treatment of AD.

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 EMW against AD were identified. These targets are mainly involved in ErbB signaling pathways including EGFR, AKT1, MAPK8, JUN, MAPK1. Molecular docking showed that EGFR, AKT1, MAPK8, JUN, MAPK1 had good binding force with EMW. In AD mice, EMW regulated the EGFR/AKT signaling through upregulation of Grb2, GAB1, Raf-1, EGFR, and AKT, and downregulation of MAPK1 and JUN, compared to that in the MD group.

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