Loperamide-induced Constipation Activates Inflammatory Signaling Pathways in the Mid Colon of SD Rats Via Complement...

Area of Science:

• Immunology
• Gastroenterology
• Molecular Biology

Background:

• Complement component 3 (C3) receptors are key inflammatory mediators in innate immunity.
• Their specific roles and mechanisms in constipation remain underexplored.

Purpose of the Study:

• To investigate the regulatory role of C3 and its receptors' downstream signaling in constipation.
• To elucidate the molecular mechanisms underlying C3-mediated inflammation in the context of constipation.

Main Methods:

• Loperamide (Lop) induced constipation in Sprague-Dawley (SD) rats.
• Measured C3, C3a receptor (C3aR), C3b receptor (C3bR) expressions.
• Assessed PI3K/AKT, RhoA/MLC, MAP kinase pathways, and inflammatory cytokine expressions in the mid colon.

Main Results:

• Lop treatment induced constipation phenotypes and altered C3 receptor expression (increased C3, decreased C3aR/C3bR).
• Upregulation of PI3K/AKT, RhoA/MLC, and MAP kinase pathways (ERK, p38) was observed.
• Increased inflammatory cytokine mRNA levels (NF-κB, TNF-α, IL-6, IL-1α) were detected.

Conclusions:

• Loperamide-induced constipation is associated with C3aR/C3bR downregulation and C3 upregulation.
• Downstream signaling pathways (PI3K/AKT, RhoA/MLC, MAP kinase) and inflammatory cytokine expression are activated.
• These findings highlight the involvement of C3 receptors and associated signaling in constipation pathophysiology.