Euphorbia humifusa Willd. alleviates ulcerative colitis by inhibiting lipid peroxidation via ACSL4/COX-2 axis

  • J Ethnopharmacol. 2026 Sep 15:368:121839. doi: 10.1016/j.jep.2026.121839.
Pengyu Dai  1 ,  Baojun Zheng  1 ,  Xinxin Pan  1 ,  Bingshuang Fan  1 ,  Yuansheng Zou  1 ,  Yufeng Yao  2 ,  Kaihui Zhang  3 ,  Rui Zhou  1 ,  Meiqi Wang  1 ,  Chenchen Zhu  4 ,  Fangle Liu  5 ,  Chaozhan Lin  6
Affiliations
  • 1. School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
  • 2. School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
  • 3. Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
  • 4. School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. Electronic address: [email protected].
  • 5. The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address: [email protected].
  • 6. School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. Electronic address: [email protected].
PMID: 42106018 DOI: 10.1016/j.jep.2026.121839
Abstract

Ethnopharmacological relevance: Herba Euphorbiae Humifusae (Euphorbia humifusa Willd., EH), named Dijincao, a traditional Chinese herbal medicine used to treat dysentery and enteritis, shows therapeutic potential for ulcerative colitis (UC), yet its mechanism remains unclear.

Aim of the study: To elucidate the efficacy of EH against UC and its mechanism.

Materials and methods: The effect of EH extract (EHE) on UC was evaluated using DSS-induced mice. Integrated analysis of metabolomics and network pharmacology based on the colonic exposure of prototypes in EHE predicted key targets and pathways involved in the treatment of UC, while molecular docking and biological experiments investigated the mechanism. Spearman's correlation analysis identified key anti-UC active components, followed by in vitro activity and mechanistic validation in RSL3-induced HCT116 cells and intestinal Organoid models.

Results: EHE alleviated UC mice in a dose-dependent manner. Network pharmacology predicted the major targets of the 18 colonic exposure components in EHE to be signaling pathways involved in inflammation and lipid metabolism. Metabolomics revealed that EHE primarily regulated glutathione metabolism and arachidonic acid metabolism. Through the integrated analysis of network pharmacology and metabolomics, suggesting that lipid peroxidation involving 11 pivotal targets may mediate the beneficial effect of EHE against UC, while molecular docking analysis and experiments substantiated that the amelioratory action of EHE partially contributed to its inhibition on ACSL4/COX-2 axis mediated lipid peroxidation. Notably, quercetin, kaempferol and naringenin, as key active constituents of EHE against UC, demonstrated the direct regulatory effect on ACSL4/COX-2 axis mediated lipid peroxidation in vitro, which was attenuated upon treatment with overexpressed ACSL4.

Conclusions: This study demonstrated that EH ameliorates UC by modulating ACSL4/COX-2 axis mediated lipid peroxidation, thereby enhancing our understanding of the mechanism underlying EH against UC.

Keywords
ACSL4; Herba euphorbiae humifusae; Lipid peroxidation; Metabolomics; Network pharmacology; Ulcerative colitis.
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