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Xiao Zhen Fang mitigates cutaneous toxicity by inhibiting PANoptosis: Insights from untargeted metabolomics and

Xin-Tian Wang1, Cheng Cheng1, Ya-Qin Li2

  • 1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.

Fitoterapia
|May 21, 2026
PubMed
Abstract

Insights

Xiao Zhen Fang (XZF) protects against EGFR inhibitor-induced skin toxicity by modulating inflammation, lipid metabolism, and PANoptosis. This traditional Chinese medicine offers a novel therapeutic strategy for drug-induced dermatotoxicity.

Area of Science:

  • Dermatology
  • Pharmacology
  • Integrative Medicine

Background:

  • Targeted cancer therapies, including epidermal growth factor receptor (EGFR) inhibitors, often cause skin toxicity, negatively impacting patient quality of life and treatment adherence.
  • Investigating protective agents against these adverse effects is crucial for improving patient outcomes and treatment compliance.

Purpose of the Study:

  • To elucidate the molecular mechanisms behind the protective effects of Xiao Zhen Fang (XZF), a traditional Chinese medicine, against EGFR inhibitor-induced dermatotoxicity.
  • To identify key pathways and biomarkers involved in XZF's therapeutic action using an integrated multi-omics approach.

Main Methods:

  • Establishment of an erlotinib-induced mouse model for cutaneous toxicity.
  • Integration of transcriptomic and serum metabolomic data to identify differentially expressed genes and metabolites.
  • Application of protein-protein interaction networks, machine learning, and pathway enrichment analyses, with validation via Western blotting and in vivo experiments examining PANoptosis and skin barrier proteins.

Main Results:

  • XZF treatment significantly reduced rash incidence, erythema, swelling, and epidermal thickness, while improving body weight in the toxicity model.
  • Multi-omics analysis identified significant alterations in inflammatory and lipid metabolism pathways, with key biomarkers related to cytokine signaling and stem cell regulation.
  • XZF suppressed upregulated PANoptosis-related proteins (e.g., Caspase-1, Gasdermin D, IL-1β) and modulated skin barrier proteins (e.g., TGM3, KRT1, KRT14), with PANoptosis confirmed as a critical mechanism.

Conclusions:

  • XZF effectively alleviates EGFR inhibitor-induced cutaneous toxicity through modulation of inflammatory signaling, lipid metabolism, stem cell regulation, and PANoptosis.
  • This study highlights PANoptosis as a novel therapeutic target for managing drug-induced skin toxicities and underscores the potential of XZF in this context.
Keywords:
DermatotoxicityMetabolomicsPANoptosisTranscriptomicsXiao Zhen fang

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