Department of Pharmacy, Noakhali Science and Technology University, Noakhali, Sonapur, 3814, Bangladesh.
Chemical Research Division, Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhaka, 1205, Bangladesh.
Inflammopharmacology. 2022 Dec;30(6):2301-2315. doi: 10.1007/s10787-022-01057-0. Epub 2022 Sep 3.
Cyclooxygenase-2 (COX-2) is an inducible enzyme that accelerates the biosynthesis of PGs during inflammation and has emerged as an important therapeutic target for anti-inflammatory drugs. Natural compounds may serve as a source of inspiration for pharmaceutical chemists and a foundation for developing innovative COX-2 inhibitors with fewer side effects. Therefore, the objective of this study was to identify the potent COX-2 inhibitor and anti-inflammatory activity of the Fimbristylis aestivalis whole plant extract (FAWE). The plant extract was found dominant with rosmarinic acid followed by catechin hydrate, syringic acid, rutin hydrate, (-) epicatechin, quercetin, myricetin, and catechol. FAWE exhibited considerable dose-dependent analgesic efficacy in all analgesic test models. FAWE also showed promising anti-inflammatory potential in carrageenan-induced inflammations in mice. This result was corroborated by molecular docking, revealing that the aforesaid natural polyphenols adopt the same orientation as celecoxib in the COX-2 active site. On the other hand, molecular dynamics (MD) simulations were performed between the most abundant components (rosmarinic acid, catechin hydrate, and syringic acid) and COX-2. Based on hydrogen bonding, RMSD, RMSF, radius of gyration, PCA, and Gibbs free energy landscape analysis, the results demonstrated that these compounds are very stable in the active site of COX-2, indicating substantial COX-2 inhibitory activity.
环氧化酶-2（COX-2）是一种诱导酶，可在炎症期间加速 PGs 的生物合成，已成为抗炎药物的重要治疗靶点。天然化合物可能成为药物化学家的灵感来源，并为开发副作用更少的新型 COX-2 抑制剂奠定基础。因此，本研究的目的是确定具有强大 COX-2 抑制作用和抗炎活性的全株夏至草提取物（FAWE）。该植物提取物以迷迭香酸为主，其次是儿茶素水合物、丁香酸、芦丁水合物、（-）表儿茶素、槲皮素、杨梅素和儿茶酚。FAWE 在所有镇痛测试模型中均表现出显著的剂量依赖性镇痛功效。FAWE 还在角叉菜胶诱导的小鼠炎症中显示出有希望的抗炎潜力。这一结果得到了分子对接的证实，表明上述天然多酚类化合物在 COX-2 活性部位与塞来昔布采用相同的取向。另一方面，进行了最丰富的成分（迷迭香酸、儿茶素水合物和丁香酸）与 COX-2 之间的分子动力学（MD）模拟。基于氢键、RMSD、RMSF、回转半径、PCA 和吉布斯自由能景观分析，结果表明这些化合物在 COX-2 的活性部位非常稳定，表明具有很强的 COX-2 抑制活性。
