Assessment of Antidiarrheal Activity of Fraxin in Chick: Synergistic Effects and Molecular Docking Study

ABSTRACT Fraxin (FRX), a natural compound, has gained attention for its potential therapeutic effects, particularly in gastrointestinal disorders. This study investigates the antidiarrheal activity of FRX in both in vivo and in silico models. In the in vivo study, chicks received FRX (5 and 10 mg/kg) alongside bismuth subsalicylate (BSS) and loperamide (LOP) as standards, assessing antidiarrheal efficacy in castor oil and magnesium sulfate‐induced diarrhea models, while the in silico study examined compounds targeting COX‐2 and MOR receptors. FRX (5 and 10 mg/kg) significantly ( p < 0.05) delayed latency and reduced diarrheal secretion in both castor oil and magnesium sulfate‐induced diarrhea models, with inhibition of up to 42.55% and 38.89%, respectively. Combination therapies (BSS‐5 + FRX‐5), (BSS‐10 + FRX‐10), and (LOP‐3 + FRX‐10) significantly ( p < 0.05) enhanced efficacy, with up to 74.47% and 75.93% inhibition, compared to individual treatments and control. In silico studies showed that FRX has a strong binding affinity for COX‐2 (−8.8 kcal/mol) and MOR (−7.1 kcal/mol) receptors. Toxicity prediction indicated lower toxicity (Class 5, LD 50 : 5000 mg/kg), and no signs of hepatotoxicity or neurotoxicity were observed. These findings suggest that FRX possesses strong antidiarrheal properties, likely mediated through COX‐2 and MOR interactions, and may serve as a promising therapeutic agent for inflammation‐related conditions in the near future.