Antiemetic activity of trans-ferulic acid possibly through muscarinic receptors interaction pathway: In vivo and in silico study

Current study was conducted to assess the effectiveness of the polyphenol trans-ferulic acid (TFA) as an antiemetic agent using in vivo and in silico methods. To evaluate this, we induced emesis in 3-day-old chicks through the oral administration of copper sulfate (CuSO4·5H2O) at a dose of 50 mg/kg. To ascertain the potential antiemetic mechanism of TFA, we employed various reference drugs such as domperidone (6 mg/kg), ondansetron (5 mg/kg), and hyoscine (21 mg/kg) as positive control groups, while the vehicle acted as a negative control group. TFA was administered orally at the doses of 25, 50 and 100 mg/kg body weight. Both the TFA and reference drug provided alone or in combined groups to assess their synergistic or antagonistic activity on the chicks. Molecular docking of TFA and the selected reference drugs was conducted against 5HT3, D2, H1, NK1, and mAChRs (M1-M5) receptors for determining binding affinity to the receptors. Active binding sites and drug-receptor interactions were predicted with the aid of various computational tools. Various pharmacokinetic features and drug-likeness of all the selected ligands were determined through the SwissADME online server. The results suggest that TFA diminishes the mean number of retches and enhances latency in the chicks at lower doses. In the combined drug therapy, TFA exhibited better antiemetic effects with ondansetron and hyoscine. In silico ADME proposed that TFA retains preferable drug-likeness and better pharmacokinetic properties to be a reliable lead. Additionally, TFA revealed the elevated binding affinity against mAChRs and the ligand (TFA) expressed the highest binding affinity (−7 kcal/mol) with the M5 receptor (6OL9). In conclusion, TFA demonstrated mild antiemetic effects in chicks, possibly through the mAChRs interaction pathway

Sclareol exerts an anti-inflammatory effect, possibly through COXs inhibition pathway: In vivo and in silico studies

Chronic and severe inflammation results in many diseases and disorders in humans. Currently, available conventional anti-inflammatory drugs have numerous mild-to-severe side effects. Thus, there is a need for safe, effective, affordable, and alternative anti-inflammatory drugs. This study aimed to evaluate the anti-inflammatory effect of sclareol (SCL), a diterpene alcohol that is the principal ingredient in the refined oil of Salvia sclarea (L.), through in vivo and in silico studies. First, we examined the individual and combined effects of SCL (5, 10, and 20 mg/kg) and standard drugs celecoxib (CXB) or ketoprofen (KPN) at 42 mg/kg (p.o.) on the formalin-induced inflammatory Swiss mice. Additionally, an in silico analysis was conducted to evaluate the potential anti-inflammatory mechanism of this study. For this, we examined the potentiality of SCL and standards to interact with cyclooxygenase (COX) -1 and COX-2 receptors. Our findings suggest that SCL exhibits a dose-dependent anti-inflammatory effect in mice. SCL-20 mg/kg significantly reduced the number of paw licks and paw edema diameters. Moreover, SCL-20 combined with CXB-42 and KPN-42 demonstrated better anti-inflammatory effects. In comparison to the standards, SCL revealed a comparable binding interaction with COX-1 and COX-2 receptors in the molecular docking study. Furthermore, SCL displayed remarkable pharmacokinetic characteristics. In conclusion, SCL significantly and dose-dependently reduced the number of paw licks and edema diameters in animals. Thus, SCL may be responsible for producing an anti-inflammatory effect by interacting with COX-1 and COX-2 receptors