Protopine-Type Alkaloids Alleviate Lipopolysaccharide-Induced Intestinal Inflammation and Modulate the Gut Microbiota

Jialu Huang1,2, Meishan Yue1,2, Yang Yang2

  • 1College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China.

Insights

Macleaya cordata alkaloids (MPTAs) show therapeutic effects in a mouse model of intestinal inflammation. MPTAs improved gut health, reduced inflammatory markers, and restored gut microbiota balance.

Area of Science:

  • Pharmacology
  • Gastroenterology
  • Microbiology

Background:

  • Intestinal inflammation is a significant health concern.
  • Lipopolysaccharide (LPS) is a potent inducer of intestinal inflammation.
  • Natural compounds are being explored for their therapeutic potential in inflammatory conditions.

Purpose of the Study:

  • To evaluate the therapeutic effects of Macleaya cordata (Willd). R. Br.-derived protopine-type alkaloids (MPTAs) on lipopolysaccharide (LPS)-induced intestinal inflammation in mice.
  • To investigate the impact of MPTAs on intestinal morphology, goblet cell abundance, inflammatory cytokine levels, and gut microbiota composition.

Main Methods:

  • Animal model: LPS-induced intestinal inflammation in mice.
  • Histological analysis: Hematoxylin and Eosin (H&E) and Periodic Acid-Schiff (PAS) staining for intestinal morphology and goblet cells.
  • Biochemical assays: ELISA for serum cytokines (IL-1β, IL-6, IL-8, TNF-α).
  • Molecular analysis: Quantitative PCR (qPCR) for mRNA expression (TLR4, NF-κB p65, NLRP3, IL-6, IL-1β) and Western blotting for protein levels (TLR4, Md-2, MyD88, NF-κB p65, NLRP3).
  • Microbiota analysis: 16S rDNA sequencing.

Main Results:

  • MPTAs treatment dose-dependently improved intestinal morphology and increased goblet cell abundance.
  • MPTAs significantly reduced serum levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α).
  • MPTAs downregulated the expression of key inflammatory pathway proteins including TLR4, MyD88, NLRP3, and NF-κB p65.
  • High-dose MPTA treatment (24 mg/kg) restored gut microbial composition.

Conclusions:

  • MPTAs possess significant therapeutic potential for treating intestinal inflammation.
  • MPTAs exert their effects by modulating inflammatory signaling pathways and improving gut barrier function.
  • MPTAs represent a promising natural therapeutic agent for inflammatory bowel diseases.

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