Jingfang granules alleviate atopic dermatitis by restoring skin barrier function and inhibiting NF-κB/NLRP3 axis and...

Atopic dermatitis (AD) is a recurrent inflammatory disease that significantly impacts patients' quality of life. Jingfang Granules (JFG) have been employed in the therapeutic management of AD and psoriasis (PSO), in contemporary clinical practice. However, further research is required to elucidate the molecular mechanisms of JFG in AD therapy.

The present study aims to explore the potential mechanisms by which JFG alleviate AD.

Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) and metabolomics were used to identify the absorbed components in the blood of JFG. BALB/c mice were continuously topically treated with 1-Chloro-2,4-dinitrobenzene (DNCB) on the dorsal skin to establish AD-mice model. The skin lesions, trans epidermal water loss (TEWL), scoring of atopic dermatitis (SCORAD), hematoxylin and eosin (H&E) staining, and inflammatory cytokines in serum were analyzed to elucidate the effects of JFG on AD. Furthermore, network pharmacology was employed to predict the potential active components and JFG targets of AD therapy. In vitro, the potential pharmacological effects of JFG toward AD were further elucidated using flow cytometry, western blot, reverse transcription-PCR (RT-PCR), immunofluorescence and enzyme linked immunosorbent assay (ELISA).

Based on UPLC-MC/MS and metabolomics, a total of 901 components were identified in serum, with 365 confirmed as JFG-derived absorbed components. These components were predominantly enriched in amino acid metabolic pathways. In vivo, JFG significantly alleviated the pathological changes, including pruritus and impairment of skin barrier function damage in AD mice, while significantly reducing TEWL, SCORAD, inflammatory cytokines release and splenic index. Network pharmacology and molecular docking analyses indicated that these potential therapeutic targets were predominantly enriched in the inflammatory response and the tumor necrosis factor (TNF) signaling pathway, which primarily involved ALB, BCL2, EGFR, GAPDH, IL6, NFKB1, STAT3 and TNF targets. Mechanistically, JFG reduced inflammatory response through NF-κB/NLRP3 axis and JAK/STAT3 axis, and restored the expression of tight junction proteins (TJPs) Occludin, Zonula occludens-1 (ZO-1) and Claudin-1, thus restoring skin barrier function and improving AD.

The present study confirmed that JFG alleviate atopic dermatitis by restoring skin barrier function and inhibiting NF-κB/NLRP3 axis and JAK/STAT3 axis. JFGs demonstrate potential therapeutic efficacy for treating AD.