霍乱是一种异常侵袭性的传染病,其特征是有可能诱发急性,丰富的,相当严重的水样腹泻和肾脏炎症。糖尿病肾病是糖尿病的严重并发症,可通过炎症导致肾功能衰竭;因此,抗炎剂是糖尿病肾病的有希望的治疗方法。以往的研究表明,花椒挥发油。黄毛竹,马钱精油(MQEO),表现出有效的抗菌,抗炎,和糖尿病小鼠的肾脏保护活性,并已成为治疗糖尿病肾病并发症的潜在治疗药物。因此,本研究旨在通过计算方法筛选霍乱毒素的潜在抑制作用和MQEO的糖尿病肾脏保护活性。来自MQEO的12种化学成分与霍乱毒素和参与糖尿病肾病的靶蛋白对接,即,TXNIP,Nrf2和DPPIV,and,随后,分子动力学模拟的预测,药物相似特性,并进行了ADMET属性。α-松油醇对霍乱毒素蛋白显示出高结合亲和力。对于TXNIP,在所有的化学成分中,α-phellandrene和p-cymene显示出与TXNIP蛋白的强结合亲和力,并在蛋白质的铰链区显示出相对稳定的柔韧性,在没有肝毒性的情况下具有良好的物理化学性质,和低细胞毒性。对于Nrf2,α-松油醇表现出最高的结合亲和力,并与Nrf2形成了非常稳定的复合物,显示出高的药代动力学特性。当与DPPIV蛋白对接时,所有化合物的自由结合能都很低,这表明了有效的生物活性。总之,基于一种计算方法,我们的发现表明,MQEO成分对霍乱毒素具有抑制活性,是抑制糖尿病炎症和治疗糖尿病肾病并发症的有前途的治疗剂。
Cholera is an exceptionally aggressive infectious disease characterized by the potential to induce acute, copious, watery diarrhea of considerable severity and renal inflammation. Diabetic nephropathy is a serious complication of diabetes mellitus that can lead to kidney failure through inflammation; thus, anti-inflammatory agents are promising therapies for diabetic nephropathy. Previous studies have shown that the essential oil of Zanthoxylum myriacanthum var. pubescens Huang, Maqian essential oil (MQEO), exhibits potent antibacterial, anti-inflammatory, and renoprotective activities in diabetic mice and has emerged as a potential therapeutic drug for the treatment of diabetic nephropathy complications. Therefore, the present study was carried out to screen the potential inhibition of cholera toxin and the diabetic renoprotective activity of MQEO through computational approaches. Twelve chemical constituents derived from MQEO were docked with cholera toxin and the target proteins involved in diabetic nephropathy, namely, TXNIP, Nrf2, and DPP IV, and, subsequently, the predictions of molecular dynamic simulations, the drug-likeness properties, and the ADMET properties were performed. α-terpineol showed high binding affinities toward the cholera toxin protein. For TXNIP, among all the chemical constituents, α-phellandrene and p-cymene showed strong binding affinities with the TXNIP protein and displayed relatively stable flexibility at the hinge regions of the protein, favorable physicochemical properties in the absence of hepatotoxicity, and low cytotoxicity. For Nrf2, α-terpineol exhibited the highest binding affinity and formed a very stable complex with Nrf2, which displayed high pharmacokinetic properties. All compounds had low free-binding energies when docked with the DPP IV protein, which suggests potent biological activity. In conclusion, based on a computational approach, our findings reveal that MQEO constituents have inhibitory activity against cholera toxin and are promising therapeutic agents for suppressing diabetic inflammation and for the treatment of diabetic nephropathy complications.