Bhuia Md Shimul, Chowdhury Raihan, Hasan Rubel, Hasan Md Sakib Al, Ansari Siddique Akber, Ansari Irfan Aamer, Mubarak Mohammad S, Coutinho Henrique D M, Domiciano Carolina Bandeira, Islam Muhammad Torequl
Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh.
BioLuster Research Center Ltd., Gopalganj, Bangladesh.
Biotechnol Appl Biochem. 2025 Feb 21. doi: 10.1002/bab.2739.
This study emphasizes to investigate the modulatory activity of trans-ferulic acid (TFA) on anti-inflammatory activity of etoricoxib (ETO) and underlying mechanisms via formalin-induced licking and paw edema model and in silico study. Inflammation was induced by injecting formalin (50 µL) into the right hind paw of mice. The animals were treated with different doses of TFA (25, 50, and 75 mg/kg, p.o.). The vehicle and ETO (35 mg/kg, p.o.) were provided as positive and negative control, respectively. ETO also served combined with TFA to evaluate the modulatory activity. The licking behavior was counted for the early and late phases, whereas the paw edema diameter was measured by using a slide caliper. All treatment was continued for 7 days until the edema was totally minimized to determine the inflammation's recovery capability for a specific group. Different computed and web tools were used to estimate molecular binding affinity, binding interactions, and pharmacokinetics. The findings demonstrated that TFA significantly (p < 0.05) enhanced the onset of licking and reduced the number of licks compared to vehicle group. TFA also showed a significant (p < 0.05) diminished in paw edema and complete recovered of the edema after 5 days of treatment indicating the anti-inflammatory effects. However, TFA with ETO notably diminished the anti-inflammatory effects of ETO by enhancing paw edema diameter and licking number. TFA also expressed elevated binding affinity of -7.5 and -6.5 kcal/mol toward nitric oxide (NO) synthase and COX-1, respectively. In conclusion, TFA exerted anti-inflammatory effects and reduces anti-inflammatory capability of ETO.
本研究着重通过福尔马林诱导的舔舐和爪肿胀模型以及计算机模拟研究，探讨反式阿魏酸（TFA）对依托考昔（ETO）抗炎活性的调节作用及其潜在机制。通过向小鼠右后爪注射福尔马林（50 μL）诱导炎症。动物分别接受不同剂量的TFA（25、50和75 mg/kg，口服）治疗。分别以溶媒和ETO（35 mg/kg，口服）作为阳性和阴性对照。ETO也与TFA联合使用以评估调节活性。对早期和晚期的舔舐行为进行计数，而爪肿胀直径则用游标卡尺测量。所有治疗持续7天，直到肿胀完全消退，以确定特定组炎症的恢复能力。使用不同的计算机和网络工具来估计分子结合亲和力、结合相互作用和药代动力学。结果表明，与溶媒组相比，TFA显著（p < 0.05）加快了舔舐发作并减少了舔舐次数。TFA还显著（p < 0.05）减轻了爪肿胀，并在治疗5天后肿胀完全消退，表明具有抗炎作用。然而，TFA与ETO联合使用时，通过增加爪肿胀直径和舔舐次数，显著减弱了ETO的抗炎作用。TFA对一氧化氮（NO）合酶和COX-1的结合亲和力分别提高到-7.5和-6.5 kcal/mol。总之，TFA具有抗炎作用，并降低了ETO的抗炎能力。
