Antiemetic effects of sclareol, possibly through 5-HT₃ and D₂ receptor interaction pathways: In-vivo and in-silico studies

Background: Emesis is a complex physiological phenomenon that serves as a defense against numerous toxins, stressful situations, adverse medication responses, chemotherapy, and movement. Nevertheless, preventing emesis during chemotherapy or other situations is a significant issue for researchers. Hence, the majority view contends that successfully combining therapy is the best course of action. In-vivo analysis offers a more comprehensive grasp of how compounds behave within a complex biological environment, whereas in-silico evaluation refers to the use of computational models to forecast biological interactions.

Objectives: The objectives of the present study were to evaluate the effects of Sclareol (SCL) on copper sulphate-induced emetic chicks and to investigate the combined effects of these compounds using a conventional co-treatment approach and in-silico study.

Methods: SCL (5, 10, and 15 mg/kg) administered orally with or without pre-treatment with anti-emetic drugs (Ondansetron (ODN): 24 mg/kg, Domperidone (DOM): 80 mg/kg, Hyoscine butylbromide (HYS): 100 mg/kg, and Promethazine hydrochloride (PRO): 100 mg/kg) to illustrate the effects and the potential involvement with 5HT₃, D₂, M₃/ACh_M, H₁, or NK₁ receptors by SCL. Furthermore, an in-silico analysis was conducted to forecast the role of these receptors in the emetic process.

Results: The results suggest that SCL exerted a dose-dependent anti-emetic effect on the chicks. Pretreatment with SCL-10 significantly minimized the number of retches and lengthened the emesis tendency of the experimental animals. SCL-10 significantly increased the anti-emetic effects of ODN and DOM. However, compared to the ODN-treated group, (SCL-10 + ODN) group considerably (p < 0.0001) extended the latency duration (109.40 ± 1.03 s) and significantly (p < 0.01) decreased the number of retches (20.00 ± 0.70), indicating an anti-emetic effect on the test animals. In in-silico analysis, SCL exhibited promising binding affinities with suggesting receptors.

Conclusion: SCL-10 exerted an inhibitory-like effect on emetic chicks, probably through the interaction of the 5HT₃ and D₂ receptors. Further studies are highly appreciated to validate this study and determine the precise mechanism(s) behind the anti-emetic effects of SCL. We expect that SCL-10 may be utilized as an antiemetic treatment in a single dosage form or that it may function as a synergist with other traditional medicines.