Rafeeq Misbahuddin, Al-Abbasi Fahad A, Afzal Muhammad, Moglad Ehssan, Al-Qahtani Salwa D, Alzrea Sami I, Almalki Naif A R, Imam Faisal, Sayyed Nadeem, Kazmi Imran
Department of Pharmacology Faculty of Medicine, Rabigh King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Pharmaceuticals (Basel). 2024 Oct 9;17(10):1348. doi: 10.3390/ph17101348.
6-Shogaol is a comparatively innovative anti-Parkinson's remedy with antioxidant and anti-inflammatory characteristics. This investigation intended to determine the role of 6-shogaol in the Parkinson's disease (PD) paradigm in rotenone-induced rats. Thirty male Wistar rats (10-12 weeks old; 180 ± 20 g) were divided into five groups. Animals with rotenone-induced experimental PD were subsequently treated with 6-shogaol-10 at 20 mg/kg for 28 days. After the experimental duration, behavioural investigations were performed, i.e., open field test, forced swim test, rotarod test, and catalepsy test. Biochemical assessments like AChE, GSH, CAT, SOD, MDA, nitrite, ceruloplasmin, proinflammatory markers such as IL-1β, NF-κB, TNF-α, and catecholamines markers (DA, GABA, and MAO-B) were determined. The docking procedure was conducted using the AutoDock Vina docking protocol. Furthermore, histopathology was performed. Rotenone significantly increased the level of MAO-B, oxidative, nitrative, and pro-inflammatory markers. However, there was a decline in ceruloplasmin, dopamine, and endogenous antioxidants. Treatment with 6-shogaol (10 and 20 mg/kg) considerably sustained the elevation of oxidative stress and inflammatory indicators and decreased AChE activity and dopamine levels. In the histology of the brain, 6-shogaol improved the neuronal structure and reduced the degeneration of neurons. Based on the binding energy values, compound 6-shogaol demonstrates a favourable binding affinity to AChE, MAO-B, DA, and GABA with respective binding energies of -8.214, -8.133, -7.396 and -6.189 kcal/mol. In this study, 6-shogaol exhibited neuroprotective properties against PD, which could be employed as a prospective medication for PD.
6-姜烯酚是一种具有抗氧化和抗炎特性的相对创新的抗帕金森病药物。本研究旨在确定6-姜烯酚在鱼藤酮诱导的大鼠帕金森病（PD）模型中的作用。将30只雄性Wistar大鼠（10 - 12周龄；180±20克）分为五组。随后，用20毫克/千克的6-姜烯酚-10对鱼藤酮诱导的实验性PD动物进行治疗，持续28天。实验结束后，进行行为学研究，即旷场试验、强迫游泳试验、转棒试验和僵住症试验。测定了乙酰胆碱酯酶（AChE）、谷胱甘肽（GSH）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、丙二醛（MDA）、亚硝酸盐、铜蓝蛋白等生化指标，以及白细胞介素-1β（IL-1β）、核因子κB（NF-κB）、肿瘤坏死因子-α（TNF-α）等促炎标志物和儿茶酚胺标志物（多巴胺（DA）、γ-氨基丁酸（GABA）和单胺氧化酶B（MAO-B））。使用AutoDock Vina对接协议进行对接程序。此外，还进行了组织病理学检查。鱼藤酮显著提高了MAO-B、氧化、硝化和促炎标志物的水平。然而，铜蓝蛋白、多巴胺和内源性抗氧化剂水平有所下降。用6-姜烯酚（10和20毫克/千克）治疗可显著抑制氧化应激和炎症指标的升高，并降低AChE活性和多巴胺水平。在脑组织学检查中，6-姜烯酚改善了神经元结构，减少了神经元的退化。基于结合能值，化合物6-姜烯酚对AChE、MAO-B、DA和GABA表现出良好的结合亲和力，各自的结合能分别为-8.214、-8.133、-7.396和-6.189千卡/摩尔。在本研究中，6-姜烯酚对PD表现出神经保护特性，可作为PD的一种潜在药物。
