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Peimisine-sulfide improves inflammation caused by copper sulfate through inhibiting ferroptosis using zebrafish

Siyu Chen1, Junyu Liang1, Tingting Lin1

  • 1State Key Laboratory of Cellular Stress Biology, Department of Endocrinology, Xiang'an Hospital of Xiamen University, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.

Journal of Environmental Sciences (China)
|March 1, 2026
PubMed

Insights

Thioylation of peimisine (PMS) to peimisine-sulfide (PMS-S) enhances safety and anti-inflammatory effects. PMS-S suppresses inflammation by inhibiting macrophage activity and ferroptosis, offering a potential therapeutic agent.

Area of Science:

  • Pharmacology and Toxicology
  • Natural Product Chemistry
  • Inflammation Research

Background:

  • Peimisine (PMS), a Fritillaria-derived compound, shows anti-inflammatory potential but suffers from poor water solubility and unclear biosafety.
  • Sulfonation yields peimisine-sulfide (PMS-S), improving solubility, but its safety and anti-inflammatory mechanisms require investigation.

Purpose of the Study:

  • To evaluate the biosafety of PMS and PMS-S using zebrafish embryo toxicity assays.
  • To elucidate the anti-inflammatory mechanism of PMS-S in a copper sulfate-induced inflammation model in zebrafish.

Main Methods:

  • Acute toxicity assays were performed on zebrafish embryos exposed to varying concentrations of PMS and PMS-S.
  • A copper sulfate-induced inflammatory model was established in transgenic zebrafish (Tg (mpeg1: EGFP)) to assess PMS-S effects.
  • Macrophage migration, reactive oxygen species (ROS) levels, and ferroptosis-related gene expression (acsl4b, fthl28) were analyzed.

Main Results:

  • PMS induced significant toxicity in zebrafish embryos at 100 µmol/L, whereas PMS-S showed no adverse effects up to 100 µmol/L.
  • PMS-S treatment suppressed macrophage migration and aggregation in the inflammatory model.
  • PMS-S reduced ROS levels and downregulated ferroptosis-related genes, indicating ferroptosis inhibition.

Conclusions:

  • Thioylation significantly enhances the biosafety profile of peimisine.
  • Peimisine-sulfide exhibits anti-inflammatory activity by suppressing macrophage activity and inhibiting ferroptosis.
  • PMS-S presents a promising candidate for therapeutic development due to its improved safety and elucidated anti-inflammatory mechanism.
Keywords:
Anti-inflammatoryBiosafetyFerroptosisPeimisine-sulfide (PMS-S)Zebrafish

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