Anti-Inflammatory Effects of Marine-Derived Resorcylic Acid Lactone Derivatives in Ulcerative Colitis via the MAPK/ERK Pathway

  • Mar Drugs. 2026 Feb 5;24(2):69. doi: 10.3390/md24020069.
Xuan Zhang  1  2  3 ,  Tuxiang Mo  1  2  3 ,  Yuyue Qin  1  2  3 ,  Meiling Le  1  2  3 ,  Li Tang  1  2  3 ,  Zhao Zhang  1  2  3 ,  Jiling Yi  1  2  3 ,  Fuling Cen  1  2  3 ,  Wanshan Li  1  2  3 ,  Guangying Chen  1  2  3
Affiliations
  • 1. Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, Hainan Normal University, Haikou 571158, China.
  • 2. Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, School of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158, China.
  • 3. Hainan Provincial International Joint Research Center for Comprehensive Utilization and Efficient Conversion of Tropical Medicinal Resources, Haikou 571158, China.
PMID: 41745472 DOI: 10.3390/md24020069
Abstract

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent inflammation of the colonic mucosa, and there is currently a lack of safe and effective treatment drugs. Resorcylic acid lactones (RALs) are a natural product that have been reported to have anti-inflammatory effects. However, the mechanism of whether RALs can treat UC and their anti-inflammatory effects remains underexplored. In this study, three new RAL derivatives, Penicillactones A-C (1-3), along with seven known analogs (4-10), were isolated from the marine fungus Penicillium sp. HN20. The structures of compounds 1-3 were elucidated by spectroscopic methods, 13C NMR theoretical calculations, and ECD analysis. Among these, compound 4 exhibited potent anti-inflammatory activity in LPS-stimulated RAW 264.7 macrophages. In a dextran sulfate sodium (DSS)-induced UC model, compound 4 alleviated body weight loss, disease activity, colon shortening, and spleen enlargement, and protected intestinal epithelial integrity. Mechanistic studies revealed that compound 4 primarily exerts its effects by downregulating the Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase (MAPK/ERK) signaling pathway, inhibiting pro-inflammatory cytokine production. Collectively, these findings provide the first evidence that marine-derived RAL derivatives exert anti-inflammatory effects by inhibiting the MAPK/ERK pathway, highlighting compound 4 as a promising therapeutic candidate for inflammation and UC.

Keywords
MAPK/ERK; Penicillium sp.; anti-inflammatory activities; marine fungi; resorcylic acid lactone; ulcerative colitis.
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