Metabolic Brain Disease ( IF 3.2 ) Pub Date : 2021-03-24 , DOI: 10.1007/s11011-021-00707-6 Uzma Saleem 1 , Aisha Shehzad 1 , Shahid Shah 2 , Zohaib Raza 1 , Muhammad Ajmal Shah 3 , Shabana Bibi 4, 5 , Zunera Chauhdary 1 , Bashir Ahmad 6
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Cucurbita pepo is used as a vegetable in Pakistan and its seeds are also rich in tocopherol. Data showed the pivotal role of tocopherol in the treatment of Parkinson’s disease (PD). The current study was designed to probe into the antiparkinson activity of methanolic extract of C. pepo (MECP) seeds in the haloperidol-induced Parkinson rat model. Behavioral studies showed improvement in motor functions. The increase in catalase, superoxide dismutase, glutathione levels whereas the decreases in the malondialdehyde and nitrite levels were noted in a dose-dependent manner. Acetylcholine-esterase (AchE) activity was increased. Molecular docking results revealed significant binding interaction of selected phytoconstituents within an active site of target protein AchE (PDB ID: 4EY7). Furthermore, α-synuclein was up regulated with down regulation of TNF-α and IL-1β in the qRT-PCR study. Subsequently, ADMET results on the basis of structure to activity predictions in terms of pharmacokinetics and toxicity estimations show that selected phytochemicals exhibited moderately acceptable properties. These properties add knowledge towards the structural features which could improve the bioavailability of selected phytochemicals before moving towards the initial phase of the drug development. Our integrated drug discovery scheme concluded that C. pepo seeds could ameliorate symptoms of PD and may prove a lead remedy for the treatment of PD.
Graphical abstract
中文翻译：
西葫芦种子的抗帕金森病活性及其可能的潜在机制
南瓜在巴基斯坦被用作蔬菜，其种子也富含生育酚。数据显示生育酚在帕金森病 (PD) 治疗中的关键作用。本研究旨在探讨C. pepo甲醇提取物的抗帕金森活性。MECP) 种子在氟哌啶醇诱导的帕金森大鼠模型中。行为研究显示运动功能有所改善。过氧化氢酶、超氧化物歧化酶、谷胱甘肽水平的增加而丙二醛和亚硝酸盐水平的降低以剂量依赖性方式被注意到。乙酰胆碱酯酶 (AchE) 活性增加。分子对接结果揭示了目标蛋白 AchE (PDB ID: 4EY7) 活性位点内所选植物成分的显着结合相互作用。此外，在 qRT-PCR 研究中，α-突触核蛋白上调，TNF-α 和 IL-1β 下调。随后，根据药代动力学和毒性估计的结构到活性预测，ADMET 结果表明，选定的植物化学物质表现出适度可接受的特性。这些特性增加了对结构特征的了解，可以在进入药物开发的初始阶段之前提高所选植物化学物质的生物利用度。我们的综合药物发现计划得出的结论是C. pepo种子可以改善 PD 的症状，并可能被证明是治疗 PD 的主要药物。
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