Ta-Xi-San Suppresses Atopic Dermatitis Involved in Multitarget Mechanism Using Experimental and Network Pharmacology...

Atopic dermatitis (AD) is a relapsing and chronic skin inflammation with a common incidence worldwide. Ta-Xi-San (TXS) is a Chinese herbal formula usually used for atopic dermatitis in clinic; however, its active compounds and mechanisms of action are still unclear. Our study was designed to reveal the pharmacological activities, the active compounds, and the pharmacological mechanisms of TXS for atopic dermatitis. Mice were induced by 2,4-dinitrocluorobenzene (DNCB) to build atopic dermatitis model. The pathological evaluation, enzyme-linked immunosorbent assay (ELISA), and hematoxylin and eosin (H&E) assay were performed. The UPLC-Q-Exactive-MS^E and network pharmacology analysis were performed to explore active ingredients and therapeutic mechanisms of TXS. TXS treatment decreased levels of immunoglobulin E (IgE), interleukin-4 (IL-4), and tumor necrosis factor-α (TNF-α) in serum induced by DNCB. TXS reduced scratching behavior and alleviated inflammatory pathology of skin and ear. Meanwhile, TXS decreased the spleen index and increased spleen index. The UPLC-Q-Exactive-MS^E results showed that 65 compounds of TXS were detected and 337 targets were fished. We collected 1371 AD disease targets, and the compound-target gene network reveled that the top 3 active ingredients were (-)-epigallocatechin gallate, apigenin, and esculetin, and the core target genes were PTGS2, PTGS1, and HSP90AA1. The KEGG pathway and GO analysis showed that TXS remedied atopic dermatitis via PI3K-Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and Toll-like receptor (TLR) signaling pathway with the regulation of inflammatory response and transcription. Further, we found that the targets of PTGS2 and HSP90AA1 were both elevated in ears and skin of AD model mouse; however, TXS decreased the elevated expressions of PTGS2 and HSP90AA1. Our study revealed that TXS ameliorated AD based on (-)-epigallocatechin gallate, apigenin, and esculetin via targeting PTGS2 and HSP90AA1.