β-Sitosterol Restored Intestinal Barrier Integrity and Reduced Intestinal Hypermotility in Stress-Induced IBS:...

Area of Science:

• Gastroenterology
• Pharmacology
• Cell Biology

Background:

• Irritable bowel syndrome (IBS) is a common disorder characterized by visceral hypersensitivity, altered intestinal motility, and compromised gut barrier function.
• Water avoidance stress (WAS) is a validated method for inducing IBS-like symptoms in rodent models, mimicking key pathological features.
• Understanding the molecular mechanisms underlying IBS, including tight junction protein expression and inflammatory pathways, is crucial for developing targeted therapies.

Purpose of the Study:

• To evaluate the therapeutic effects of β-sitosterol and sertraline on colonic motility, barrier integrity, inflammation, and endotoxemia in a rat model of IBS.
• To investigate the impact of these compounds on the expression of tight junction proteins (Claudin-1, Claudin-2) and the chloride channel (ClC-2).
• To assess the potential of β-sitosterol and sertraline as targeted treatments for IBS by analyzing their effects on gut healing and inflammatory markers.

Main Methods:

• Induction of IBS-like symptoms in Wistar rats using a 10-day water avoidance stress (WAS) protocol.
• Administration of β-sitosterol (25 mg/kg/day) or sertraline (30 mg/kg/day) to WAS-exposed rats, with appropriate control groups.
• Assessment of colonic motility (fecal output, water content, transit time), gut barrier integrity (tight junction protein expression via QRT-PCR), inflammation (TNF-α levels), and endotoxemia (serum LPS levels).

Main Results:

• WAS significantly increased fecal output, water content, and intestinal transit, confirming IBS-like hypermotility and diarrhea.
• Both β-sitosterol and sertraline reduced fecal output and water content; β-sitosterol uniquely normalized intestinal transit.
• β-sitosterol restored Claudin-1/2 expression and upregulated ClC-2, while sertraline increased Claudin-1 and ClC-2 but did not affect Claudin-2. Both agents reduced colonic TNF-α and serum LPS levels.
• β-sitosterol significantly preserved colonic crypt architecture and mucosal integrity, whereas sertraline improved wall thickness but did not prevent erosion.

Conclusions:

• β-sitosterol effectively alleviates IBS symptoms, including hypermotility, restores intestinal barrier integrity, reduces inflammation, and prevents endotoxemia in a WAS-induced rat model.
• Modulation of ClC-2 expression and promotion of mucosal healing by β-sitosterol highlight its potential as a targeted therapy for IBS.
• While sertraline demonstrates anti-inflammatory effects, β-sitosterol shows superior efficacy in restoring gut barrier function and overall IBS symptom management.