Astragalus mongholicus Bunge extract improves ulcerative colitis by promoting PLCB2 to inhibit colonic epithelial cell pyroptosis

J Ethnopharmacol. 2024 Nov 15:334:118554. doi: 10.1016/j.jep.2024.118554. Epub 2024 Jul 9.

Abstract

Ethnopharmacological relevance: Astragalus mongholicus Bunge (AM) and its active ingredients are mainly used for anti-inflammatory, antiviral, antioxidant, immune regulation, cardiovascular and nervous system protection, anti-cancer, anti-tumor and so on.

Aim of the study: To explore the Astragalus mongholicus Bunge extract pharmacological mechanisms and biology processes which improves ulcerative colitis (UC).

Materials and methods: Dextran sulfate sodium (DSS)-induced UC models in C57BL/6 mice were established, and the mice were treated with Astragalus mongholicus Bunge extract or salazosulfapyridine (SASP). DSS-induced mice- and human-derived colonic epithelial cell lines were used to reveal the inflammatory environment of UC. After treatment with Astragalus mongholicus Bunge extract, the expression of phospholipase C-β 2 (PLCB2) in the cells was detected by quantitative real-time PCR (qRT-PCR), and cell proliferative activity was detected by cell counting kit 8 (CCK-8) assay. Finally, the levels of pyroptosis-related inflammatory factors in cell culture supernatants was detected by ELISA.

Results: Treatment of UC mice with Astragalus mongholicus Bunge extract do significantly improved DAI scores and histopathological damage scores, and decreased the levels of Eotaxin, GCSF, KC, MCP-1, TNF-α, and IL-6. Besides, Astragalus mongholicus Bunge extract inhibited the expression of nucleotide-binding oligomerization segment-like receptor family 3 (NLRP3), cleaved Caspase-1, and GSDMD-N in the colonic tissues, and reduced the levels of inflammation-related factors IL-1β and IL-18 in serum and tissues. In vitro, Astragalus mongholicus Bunge extract partially reversed the DSS-induced reduction of PLCB2 expression in CP-M030 and NCM460, promoted cell proliferative activity, and reduced the levels of IL-1β and IL-18.

Conclusions: In DDS-induced UC mice, Astragalus mongholicus Bunge extract improves ulcerative colitis by inhibiting colonic epithelial cell pyroptosis through PLCB2 promotion.

Keywords: Astragalus mongholicus bunge extract; Inflammation; PLCB2; Pyroptosis; Transcriptomic analysis; Ulcerative colitis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Astragalus Plant* / chemistry
  • Cell Line
  • Cell Proliferation / drug effects
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / pathology
  • Colon* / drug effects
  • Colon* / metabolism
  • Colon* / pathology
  • Dextran Sulfate*
  • Disease Models, Animal
  • Epithelial Cells* / drug effects
  • Epithelial Cells* / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Plant Extracts* / pharmacology
  • Pyroptosis* / drug effects

Substances

  • Plant Extracts
  • Dextran Sulfate
  • Anti-Inflammatory Agents