Phull Abdul Rehman, Hassan Mubshir, Abbas Qamar, Raza Hussain, Haq Ihsan Ul, Seo Sung Yum, Kim Song Ja
Department of Biological Sciences, College of National Sciences, Kongju National University, 56 Gongju daehak-Ro, Gongju, 32588, Korea.
Department of Physiology, University of Sindh, Jamshoro, 76080, Pakistan.
Chem Biodivers. 2018 Jan;15(1). doi: 10.1002/cbdv.201700427. Epub 2018 Jan 8.
Urease enzyme plays a crucial role in the survival of Helicobacter pylori that contributes to different diseases, including peptic ulcer (gastric and duodenal ulcers). Coagulansin A is the steroidal lactone (withanolide) found in plants of solanaceae family such Withania coagulans. The current study was carried out to examine the in vitro urease, COX-2 inhibitory activity and effect on type II collagen expression of coagulansin A. Moreover, we investigated cytotoxic effects on rabbit articular chondrocytes through MTT assay. COX-2 and type II collagen expressions were determined through a Western blot method. Molecular docking and simulation studies of urease (PDBID 4H9M) and COX-2 (PDBID 5F1A) proteins were also performed as an in silico approach. Results showed that COX-2 expression was decreased dose dependably, significantly higher expression of type II collagen was observed at higher doses. In the current study, coagulansin A was found as non-toxic, and showed notable urease inhibitory activity in non-competitive manner with IC 23.14 μm in comparison to reference drug thiourea 17.81 μm. Significant decrease in COX-2 expression (40%) and increase in type II collagen (20%) were observed as compared to control. In silico results unveiled the strong binding affinities of coagulansin A with both of these urease and COX-2 proteins. Therefore, herein we proposed the significant antiurease potential of this compound that could be used in treating different diseases such as ulcers. Moreover, detailed in vivo studies and molecular mechanism based studies are suggested.
脲酶在幽门螺杆菌的生存中起着关键作用，幽门螺杆菌会引发包括消化性溃疡（胃溃疡和十二指肠溃疡）在内的多种疾病。凝固素A是一种甾体内酯（withanolide），存在于茄科植物如凝乳茄中。本研究旨在检测凝固素A的体外脲酶、COX - 2抑制活性以及对II型胶原蛋白表达的影响。此外，我们通过MTT法研究了其对兔关节软骨细胞的细胞毒性作用。通过蛋白质印迹法测定COX - 2和II型胶原蛋白的表达。还采用计算机模拟方法对脲酶（PDBID 4H9M）和COX - 2（PDBID 5F1A）蛋白进行了分子对接和模拟研究。结果表明，COX - 2表达呈剂量依赖性降低，在较高剂量下观察到II型胶原蛋白表达显著升高。在本研究中，发现凝固素A无毒，与参考药物硫脲（IC为17.81μm）相比，以非竞争性方式显示出显著的脲酶抑制活性，IC为23.14μm。与对照组相比，观察到COX - 2表达显著降低（40%），II型胶原蛋白增加（20%）。计算机模拟结果揭示了凝固素A与这两种脲酶和COX - 2蛋白都具有很强的结合亲和力。因此，我们在此提出该化合物具有显著的抗脲酶潜力，可用于治疗如溃疡等不同疾病。此外，建议进行详细的体内研究和基于分子机制的研究。
