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

Abstract

Background: This study emphasizes evaluating the antiemetic efficacy of the natural food component caffeic acid (CAF) using a copper sulfate pentahydrate (CuSO4.5H2O)-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 D2 (−7.3 kcal/mol), 5HT3 (−7.1 kcal/mol), and M5 (−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 D2, 5TH3, and M5 receptors. Therefore, several preclinical and clinical studies are necessary to assess the effectiveness and safety profile of this food ingredient.