Paeoniflorin abrogates DSS-induced colitis via a TLR4-dependent pathway

Area of Science:

• Pharmacology
• Immunology
• Gastroenterology

Background:

• Paeonia lactiflora Pall (peony) has a long history of medicinal use.
• Paeoniflorin is the main active compound in peony root.
• Paeoniflorin shows potential anti-colitis activity, but its mechanism is not fully understood.

Purpose of the Study:

• To investigate the molecular mechanism of paeoniflorin in treating dextran sulfate sodium (DSS)-induced colitis.
• To explore paeoniflorin's effects on inflammatory pathways and key receptors in colitis models.

Main Methods:

• Administered paeoniflorin to mice with DSS-induced colitis.
• Assessed inflammatory markers (MPO, TNF-α, IL-6) and gene expression.
• Examined the activation of NF-κB, MAPK pathways, and Toll-like receptor (TLR) expression.
• Utilized cell-based assays with mouse macrophages (RAW264.7) and human colon cancer cells (HT-29).
• Performed TLR4 knockdown and overexpression experiments.

Main Results:

• Paeoniflorin significantly reduced colitis severity and inflammatory parameters in vivo.
• It downregulated myeloperoxidase (MPO) activity, TNF-α, and IL-6 levels.
• Paeoniflorin suppressed the activation of NF-κB and MAPK pathways, correlating with decreased Toll-like receptor 4 (TLR4) expression.
• In vitro, paeoniflorin reduced TLR4 expression, inhibited NF-κB activation, and decreased IL-6 production in LPS-stimulated cells.
• TLR4 was essential for paeoniflorin's anti-inflammatory effects.

Conclusions:

• Paeoniflorin effectively attenuates DSS-induced colitis.
• The mechanism involves the downregulation of TLR4 expression.
• Paeoniflorin suppresses NF-κB and MAPK signaling pathways, leading to reduced inflammation.