Multi-omics analysis revealed that Jingfang Mixture alleviates inflammation in an OVA/Al(OH)₃-induced urticaria-like rat model by regulating the AMPK/p38 MAPK/PI3K-Akt pathway associated with the gut-skin axis.

Authors

Xiaowen Song, Xuexin Liu, Le Yang, Guangli Yan, Hui Sun, Ye Sun, Guimin Zhang, Ling Kong, Ying Han, Yongxia Guan, Xijun Wang

Published in

Frontiers in cellular and infection microbiology. Volume 16. Pages 1973292. Epub Oct 29, 2026.

Abstract

The systemic and relapsing nature of urticaria cannot be fully explained by cutaneous mast-cell activation alone. Whether the gut contributes, and whether a multi-component formula such as Jingfang Mixture (JF) acts through a gut-skin route, have not been tested together at the level of microbiota, metabolites, and skin signaling together.
Using an OVA (ovalbumin)/Al(OH)₃-induced urticaria-like allergic inflammation rat model, we integrated 16S rRNA gene sequencing, fecal untargeted metabolomics, and skin DIA (data-independent acquisition)-based quantitative proteomics to investigate the therapeutic mechanisms of JF.
JF suppressed both Th2 (IgE (immunoglobulin E), IL-4 (interleukin-4)) and Th17/pro-inflammatory (IL-6 (interleukin-6), TNF-α (tumor necrosis factor-α), IL-17 (interleukin-17)) responses, improved intestinal barrier-associated abnormalities, and partially reversed gut dysbiosis by restoring SCFA-producing bacteria (Bacteroidia, Clostridia, Lachnospirales, Oscillospirales) while reducing Proteobacteria and Enterobacterales. JF normalized the fecal metabolome, elevating anti-inflammatory metabolites including butyrate, indole, indole-3-acetic acid, docosahexaenoic acid (DHA) and reducing pro-inflammatory mediators such as arachidonic acid, leukotriene B4, secondary bile acids. At the skin level, JF activated AMPK (AMP-activated protein kinase) signaling and suppressed aberrant p38 MAPK (p38 mitogen-activated protein kinase) and PI3K (phosphoinositide 3-kinase)-Akt (protein kinase B) activation. Spearman correlation analysis further revealed that SCFAs (short-chain fatty acids) and indole derivatives were positively correlated with the abundance of AMPK-pathway-related proteins and negatively with p38 MAPK and PI3K-Akt proteins, whereas pro-inflammatory metabolites exhibited inverse correlation patterns.
Collectively, our findings indicate that JF mitigates urticaria-like inflammation, likely through gut microbiota and modulating SCFA, bile acid, tryptophan, and lipid metabolism. This multi-omics evidence suggests that JF may act through the gut microbiota-metabolite-skin signaling axis to confer anti-urticarial benefits. Nevertheless, further causal validation experiments and clinical investigations are warranted.

PMID:
43021907
Bibliographic data and abstract were imported from PubMed on 13 Nov 2026.

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