Prokinetic effect of ferulic acid ethyl ester on gastrointestinal motility in mice: an integrated in silico and in vivo study

Gastrointestinal paralysis and dysmotility remain clinically relevant conditions associated with delayed intestinal transit, feeding intolerance, prolonged hospitalization, and limited effective pharmacological treatment options. Among these disorders, postoperative ileus (POI) is a common complication after abdominal surgery characterized by transient suppression of coordinated gastrointestinal motility. The present study investigated the effects of ferulic acid ethyl ester (FAEE) on intestinal motility and explored its underlying mechanisms using integrated in silico and in vivo approaches. Gastrointestinal transit was assessed in mice by the charcoal meal test under normal conditions and in an experimental POI model induced by intestinal manipulation. In normal mice, FAEE (50 and 100 mg/kg, p.o.) significantly increased intestinal transit. In POI animals, FAEE (50 mg/kg) significantly attenuated the postoperative delay in intestinal transit. Biochemical analyses showed that FAEE reduced MPO activity, NOx, and MDA levels, while restoring SOD activity and GSH content. Pharmacological studies further indicated that the prokinetic effect of FAEE involves cholinergic and calcium-dependent pathways, as atropine and verapamil significantly attenuated its effects. In contrast, pharmacological blockade of opioid and 5-HT3 receptors did not significantly alter the prokinetic effect of FAEE under the present experimental conditions. Molecular docking predicted favorable binding of FAEE to M3R and CaV1.2. In conclusion, FAEE exerts prokinetic effects and attenuates the development of postoperative dysmotility, with findings suggesting the involvement of cholinergic and calcium-dependent pathways and an association with anti-inflammatory and antioxidant effects.