Mowla Tajbiha E, Zahan Sumyya, Sami Saad Ahmed, Naim Uddin S M, Rahman Minhajur
Department of Pharmacy, University of Chittagong, Chattogram 4331, Bangladesh.
Department of Pharmacy, Southern University Bangladesh, Chattogram 4210, Bangladesh.
Saudi J Biol Sci. 2022 May;29(5):3791-3805. doi: 10.1016/j.sjbs.2022.03.008. Epub 2022 Mar 9.
Multidrug-resistant bacterial infections, helminthiasis, thrombosis, anxiety and insomnia are some of the major global health concerns. (L.) Hepper (VM) has been used traditionally to treat microbial infection, helminthic disorder, schizophrenia, memory loss, and blood circulatory problem. This research aims to discover antibacterial, anthelmintic, thrombolytic and neuropharmacological effects of the methanol extract of seeds (MESVM), and also in-silico prediction of relevant lead compounds by molecular docking and ADME/T analysis. The crude extracts and subsequent fractions of MESVM were investigated for antibacterial activity by disc diffusion method, anthelmintic activity by paralysis and death test on earthworms, and thrombolytic activity by in vitro blood clot dissolution test. Open-field test and elevated plus maze test were performed for evaluating anxiolytic activity of the extracts. Using molecular docking, ligand poses of selected VM seeds' phytoconstituents were predicted targeting tubulin, GlcN-6-P synthase, and human tissue plasminogen activator proteins for anthelmintic, antibacterial, and thrombolytic activity, respectively. In the antibacterial activity test, the MESVM at 10000 μg/mL concentration created highest and significant (P < 0.001) zone of inhibition against (15.42 mm) and (12 mm) compared with tetracycline. The MESVM exhibited remarkable anthelmintic activity at 50 mg/mL concentration with 35.4 min paralysis time, 75.2 min death time and were closer to the durations of standard drug albendazole. No test extract showed anxiolytic activity. In thrombolytic activity test, all concentrations of MESVM produced clot lytic activity with high significance (P < 0.001) in comparison with the blank. In docking, 2'-hydroxygenistein, cyclokievitone hydrate, and aureol displayed maximum affinity to the target proteins for anthelmintic, antibacterial, and thrombolytic activity, respectively. This research revealed that the MESVM demonstrated potential anthelmintic, antibacterial and thrombolytic effects that confirmed the folkloric uses of VM and the found relevant lead compounds might be further optimized in future drug development.
多重耐药细菌感染、蠕虫病、血栓形成、焦虑和失眠是一些主要的全球健康问题。传统上，(L.) Hepper (VM) 已被用于治疗微生物感染、蠕虫病、精神分裂症、记忆力减退和血液循环问题。本研究旨在发现种子甲醇提取物 (MESVM) 的抗菌、驱虫、溶栓和神经药理学作用，并通过分子对接和ADME/T分析对相关先导化合物进行计算机模拟预测。通过纸片扩散法研究MESVM的粗提物及其后续馏分的抗菌活性，通过对蚯蚓的麻痹和死亡试验研究驱虫活性，通过体外血凝块溶解试验研究溶栓活性。进行旷场试验和高架十字迷宫试验以评估提取物的抗焦虑活性。使用分子对接，分别针对微管蛋白、GlcN-6-P合酶和人组织纤溶酶原激活蛋白预测所选VM种子植物成分的配体构象，以实现驱虫、抗菌和溶栓活性。在抗菌活性试验中，与四环素相比，浓度为10000μg/mL的MESVM对(15.42mm)和(12mm)产生了最高且显著(P<0.001)的抑菌圈。MESVM在浓度为50mg/mL时表现出显著的驱虫活性，麻痹时间为35.4分钟，死亡时间为75.2分钟，接近标准药物阿苯达唑的持续时间。没有测试提取物显示出抗焦虑活性。在溶栓活性试验中，与空白相比，所有浓度的MESVM均产生了具有高度显著性(P<0.001)的凝块溶解活性。在对接中，2'-羟基染料木素、环基维酮水合物和奥雷醇分别对驱虫、抗菌和溶栓活性的靶蛋白表现出最大亲和力。本研究表明，MESVM具有潜在的驱虫、抗菌和溶栓作用，证实了VM的民间用途，并且所发现的相关先导化合物可能在未来的药物开发中得到进一步优化。
