Kratom syrup reduces colitis severity and enhances intestinal barrier integrity in acetic acid-induced colitis mice

• Kratom syrup (KS) significantly ameliorated colitis symptoms in colitis mice. • KS delayed upper intestinal transit and improved total gut transit time. • KS improved paracellular permeability in the distal colon in colitis mice. • This study provides in vivo evidence supporting the traditional use of kratom. Kratom ( Mitragyna speciosa ) is traditionally used in Thailand for its anti-diarrheal effects, yet its potential in colitis therapy remained unexplored. This study evaluated the therapeutic efficacy of kratom syrup (KS) containing kratom extract in an acetic acid-induced colitis mouse model. Colitis was induced in ICR mice via intrarectal administration of 5% v/v acetic acid. Mice were treated orally with KS at mitragynine-equivalent doses of 5, 10, and 20 mg/kg for five days. A positive control group received 4 mg/kg of loperamide syrup (LS). Colitis severity was assessed using the disease activity index (DAI), gastrointestinal transit assays, and colon length measurement. Paracellular permeability in the proximal and distal colons were evaluated using the Ussing chamber technique [transepithelial electrical resistance (TEER), short-circuit current (Isc), potential difference (PD), and permeability coefficient (P app )]. Claudin-2 and occludin expression levels were determined by Western blotting. KS significantly reduced DAI scores and prolonged gastrointestinal transit time. The 10 mg/kg dose (KS10) markedly delayed upper intestinal transit and improved total gut transit time. Both KS5 and KS10, but not LS or KS20, restored colon length. KS treatment enhanced distal colon barrier function, as shown by increased TEER and reduced P app , and normalized claudin-2 and occludin expressions. KS alleviated colitis symptoms by reducing disease severity, enhancing epithelial barrier integrity, and relieving diarrhea. These finding provide novel evidence supporting kratom-based formulations as promising alternatives for colitis management.