Therapeutic effects of D-cycloserine in mouse models of IBD and CAC: Targeting NLRP3 inflammasome and intestinal barrier integrity

  • Int Immunopharmacol. 2025 Jul 14:163:115209. doi: 10.1016/j.intimp.2025.115209.
Shengwei Chen  1 ,  Lizhuowen Yan  2 ,  Jingtao Zeng  2 ,  Wei Meng  2 ,  Jionghan Zhuang  2 ,  Fengying Chen  3 ,  Yonglong Guo  2 ,  A M Abd El-Aty  4 ,  Xianghong Ju  3 ,  Shihua Yang  5
Affiliations
  • 1. College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Shenzhen Institute of Guangdong Ocean University, Organization X, Shenzheng 518000, China; College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China.
  • 2. College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
  • 3. Shenzhen Institute of Guangdong Ocean University, Organization X, Shenzheng 518000, China; College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang 524088, China.
  • 4. Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt; Department of Medical Pharmacology, Faculty of Medicine, Atatürk University, Erzurum 25240, Turkey.
  • 5. College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address: [email protected].
PMID: 40663810 DOI: 10.1016/j.intimp.2025.115209
Abstract

D-Cycloserine (DCS), a broad-spectrum Antibiotic and NMDA Receptor Modulator, exhibits immunomodulatory effects beyond its known neurological and antimicrobial functions. This study investigated DCS's therapeutic potential in inflammatory bowel disease (IBD) and colitis-associated colorectal Cancer (CAC) using in vitro and in vivo models. In lipopolysaccharide (LPS)-stimulated NCM460 cells, DCS inhibited NLRP3 inflammasome activation and restored tight junction protein expression. In dextran sulfate sodium (DSS)-induced murine colitis, both preventive and therapeutic DCS regimens attenuated inflammation, reduced histopathological damage, and preserved intestinal barrier integrity. In azoxymethane (AOM)/DSS-induced CAC, DCS decreased tumor burden and reduced Ki-67+ cell proliferation without systemic toxicity. These findings position DCS as a promising dual-target candidate for IBD and CAC management through NLRP3-caspase-1-GSDMD pathway inhibition and epithelial barrier maintenance.

Keywords
CAC; D-cycloserine; IBD; NLRP3-caspase1-GSDMD; Tight junction proteins.
Products