Plants of the Achillea genus have traditionally been employed to manage digestive disorders. This study aimed to investigate the mechanisms underlying the effects of the decocted extract of Achillea odorata L. (ADE), particularly its influence on neurotransmitters regulating gastrointestinal motility, as well as its impact on intestinal transit (IT) and gastric emptying (GE). Mice were administered ADE at doses of 100, 200, or 400 mg·kg⁻¹, followed one hour later by a phenol red meal. In a separate set of experiments, rats received ADE (200 mg·kg⁻¹) along with pharmacological agents including atropine (3.45 mmol·kg⁻¹), L-Nitro-N-Arginine (L-NNA) (1.36 mmol·kg⁻¹), or indomethacin (5.58 mmol·kg⁻¹) to evaluate its effects on IT and GE. ADE significantly reduced GE and IT at all tested doses, with GE values of 45.62±2.69 percent, 42.92±4.91 percent, and 28.80±3.02 percent, and IT values of 57.87±3.97 percent, 48.72±2.01 percent, and 42.81±3.96 percent, respectively. The observed delay in GE and antimotility effects were mediated via cholinergic, nitric oxide, and cyclooxygenase pathways. High-performance liquid chromatography with photodiode array detection (HPLC–DAD) identified 12 phenolic acid compounds in ADE, with chlorogenic acid being the most abundant at 33.43±0.18 mg·g⁻¹. These findings indicate that components of A. odorata L. could offer therapeutic potential in managing gastrointestinal motility disorders, such as diarrhea.
