Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh.
BioLuster Research Center, Gopalganj, Dhaka, 8100, Bangladesh.
Sci Rep. 2024 Mar 19;14(1):6642. doi: 10.1038/s41598-024-57173-0.
The present study was designed to evaluate the antiemetic activity of abietic acid (AA) using in vivo and in silico studies. To assess the effect, doses of 50 mg/kg b.w. copper sulfate (CuSO⋅5HO) were given orally to 2-day-old chicks. The test compound (AA) was given orally at two doses of 20 and 40 mg/kg b.w. On the other hand, aprepitant (16 mg/kg), domperidone (6 mg/kg), diphenhydramine (10 mg/kg), hyoscine (21 mg/kg), and ondansetron (5 mg/kg) were administered orally as positive controls (PCs). The vehicle was used as a control group. Combination therapies with the referral drugs were also given to three separate groups of animals to see the synergistic and antagonizing activity of the test compound. Molecular docking and visualization of ligand-receptor interaction were performed using different computational tools against various emesis-inducing receptors (D, D, 5HT, H, and M-M). Furthermore, the pharmacokinetics and toxicity properties of the selected ligands were predicted by using the SwissADME and Protox-II online servers. Findings indicated that AA dose-dependently enhances the latency of emetic retching and reduces the number of retching compared to the vehicle group. Among the different treatments, animals treated with AA (40 mg/kg) exhibited the highest latency (98 ± 2.44 s) and reduced the number of retching (11.66 ± 2.52 times) compared to the control groups. Additionally, the molecular docking study indicated that AA exhibits the highest binding affinity (- 10.2 kcal/mol) toward the M receptors and an elevated binding affinity toward the receptors 5HT (- 8.1 kcal/mol), M (- 7.7 kcal/mol), M (- 8.7 kcal/mol), and H (- 8.5 kcal/mol) than the referral ligands. Taken together, our study suggests that AA has potent antiemetic effects by interacting with the 5TH and muscarinic receptor interaction pathways. However, additional extensive pre-clinical and clinical studies are required to evaluate the efficacy and toxicity of AA.
本研究旨在通过体内和计算研究评估枞酸（AA）的止吐活性。为了评估效果，给 2 日龄小鸡口服 50mg/kg b.w.硫酸铜（CuSO4·5H2O）。受试化合物（AA）以 20 和 40mg/kg b.w.的两个剂量口服给予。另一方面，阿瑞匹坦（16mg/kg）、多潘立酮（6mg/kg）、苯海拉明（10mg/kg）、氢溴酸东莨菪碱（21mg/kg）和昂丹司琼（5mg/kg）作为阳性对照（PC）口服给予。载体用作对照组。还向三组动物给予联合治疗药物，以观察测试化合物的协同和拮抗活性。使用不同的计算工具针对不同的致吐受体（D、D、5HT、H 和 M-M）进行分子对接和配体-受体相互作用的可视化。此外，使用 SwissADME 和 Protox-II 在线服务器预测所选配体的药代动力学和毒性特性。研究结果表明，AA 剂量依赖性地增加呕吐性干呕的潜伏期并减少与载体组相比的干呕次数。在不同的治疗中，与对照组相比，用 AA（40mg/kg）治疗的动物表现出最长的潜伏期（98±2.44s）和减少的干呕次数（11.66±2.52 倍）。此外，分子对接研究表明，AA 对 M 受体表现出最高的结合亲和力（-10.2kcal/mol），并且对 5HT（-8.1kcal/mol）、M（-7.7kcal/mol）、M（-8.7kcal/mol）和 H（-8.5kcal/mol）受体的结合亲和力高于参考配体。总之，我们的研究表明，AA 通过与 5HT 和毒蕈碱受体相互作用途径相互作用具有有效的止吐作用。然而，需要进行更多的临床前和临床研究来评估 AA 的疗效和毒性。
