Exploring the antiemetic potential of ascorbic acid: a combined animal behavior and in silico approach targeting 5-HT 3 and D2 receptors

Abstract

Emesis, or vomiting, is a reflex involving the forceful expulsion of stomach contents, often triggered by various physiological and psychological factors. The current study was conducted to evaluate the antiemetic properties of ascorbic acid (AA) using both in vivo and in silico approaches. In this study, emesis was triggered in chicks by administering copper sulfate pentahydrate (CuSO4⋅5H2O) orally. AA was given orally at 25, 50 and 100 mg/kg and compared with reference drugs domperidone (7 mg/kg), ondansetron (5 mg/kg), and with a vehicle negative control. We also performed in silico study to investigate the potential interactions of AA with D2 and 5HT3 receptors and assess its toxicity. Results showed that AA, particularly at 100 mg/kg, significantly delayed the onset of retching (73.75 ± 8.13 seconds) and reduced retch frequency (15.00 ± 3.36 times) over a 10 min period, with enhanced efficacy when combined with standard antiemetics. Docking studies revealed favorable binding affinity (− 5.3 and − 5.4 kcal/mol, respectively) and greater hydrogen bond (HB) interactions between AA and both receptors, suggesting a dual antagonistic mechanism. Also displayed favorable toxicological profile. This study underscores the potential of AA as an effective and safe antiemetic agent, warranting further investigation into its therapeutic application.