β‐Sitosterol Restored Intestinal Barrier Integrity and Reduced Intestinal Hypermotility in Stress‐Induced IBS: Comparison With Sertraline

Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity, intestinal hypermotility, and impaired barrier integrity. This study evaluated the effects of β-sitosterol and sertraline on colonic motility, tight junction proteins and chloride channel (ClC-2) expression, intestinal inflammation and endotoxemia in water avoidance stress (WAS)-induced rat model of IBS. Thirty-five male Wistar rats were divided into five groups (n = 7/group): control, WAS+β-sitosterol (25 mg/kg/day in olive oil), WAS + sertraline (30 mg/kg/day in saline), WAS + olive oil and WAS + saline groups. WAS (10 days) was used to induce IBS-like symptoms in rats. Fecal pellet output (FPO), fecal water content (FWC), and intestinal transit were assessed to determine motility and diarrhea. QRT-PCR quantified Claudin-1, Claudin-2, and ClC-2 mRNA expression. Endotoxemia and intestinal inflammation were assessed by measuring serum lipopolysaccharide (LPS) and colonic TNF-α level. WAS significantly increased FPO, FWC, and accelerated intestinal transit compared to control. Treatment with both β-sitosterol and sertraline reduced FPO and FWC compared to untreated IBS rats. β-sitosterol (but not sertraline) normalized intestinal transit. WAS significantly upregulated Claudin-2 and downregulated Claudin-1 compared to control. β-sitosterol restored Claudin-1/2 expression and upregulated ClC-2 above control levels. Sertraline increased Claudin-1 and ClC-2 but did not affect Claudin-2 compared to untreated IBS group. WAS caused significant colonic inflammation with a threefold TNF-α increase, confirming an IBS-like state. Sertraline and β-sitosterol significantly reduced TNF-α in colon tissue. β-sitosterol significantly reduced serum LPS and preserved colonic crypt architecture, wall thickness, and mucosa compared to untreated IBS group. Sertraline reduced TNF-α, LPS and improved wall thickness but did not affect crypt architecture or prevent erosion. β-Sitosterol alleviated hypermotility, restored barrier integrity, reduced inflammation and prevented endotoxemia. ClC-2 modulation and mucosal healing of β-sitosterol suggest its potential as a targeted IBS therapy.