Exploring the Antiemetic Potential of Caffeic Acid: A Combined In Vivo and Computational Approach.

Background: This study emphasizes evaluating the antiemetic efficacy of the natural food component caffeic acid (CAF) using a copper sulfate pentahydrate (CuSO.5HO)-induced emetic model on chicks, and an in silico approach was also adopted to estimate the possible underlying mechanisms.

Methods: Two doses (25 and 50 mg/kg b.w.) of CAF and several referral drugs considered positive controls (PCs), including domperidone (6 mg/kg), hyoscine (21 mg/kg), aprepitant (16 mg/kg), diphenhydramine (10 mg/kg), and ondansetron (5 mg/kg), were orally administered to chicks. The vehicle served as the control group. Co-treatments of CAF with referral drugs were also provided to chicks to evaluate the modulatory action of the test compound.

Results: According to the results, CAF delayed the emetic onset and decreased the frequency of retches in a dose-dependent manner compared to the vehicle group. CAF (40 mg/kg) represented a notable delayed latency period (60.17 ± 3.16 s) and a diminished number of retchings (18.33 ± 1.74 times) compared to the control group. Further, in the co-treatments, CAF increased the latency period and reduced the number of retches, except for domperidone. In the in silico investigation, CAF showed notable binding affinity toward the D (-7.3 kcal/mol), 5HT (-7.1 kcal/mol), and M (-7 kcal/mol) receptors in the same binding site as the referral ligand.

Conclusion: This research indicated that CAF has mild antiemetic properties by interacting with the D, 5TH, and M receptors. Therefore, several preclinical and clinical studies are necessary to assess the effectiveness and safety profile of this food ingredient.