Plumbagin's Healing Effect on Motor Impairment in Rotenone-toxified Rodents.

Aanchal Verma, Ahsas Goyal
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Abstract

Background: Parkinson's disease is an illness marked by a gradual mitigation of dopamine neurons within the substantia nigra, which eventually leads to a deficiency of dopamine that further gives rise to mobility as well as cognitive impairments. Through long-established traditions, a wide array of Traditional Chinese Medicines (TCM) have undergone testing and are employed to avoid neurodegenerative disorders. Plumbagin is the primary active component of a medication called Baihua Dan or Plumbago zeylanica L., which is clinically used in China.

Objectives: This study investigated plumbagin-induced alterations in a Parkinson's disease rat model instigated by subcutaneous rotenone injection.

Methods: Male rats were administered subcutaneous injections of rotenone at a dosage of 1.5 mg/kg, followed by the treatment with varying doses of plumbagin (10, 20, and 40 mg/kg) through the oral route. The rats underwent various motor ability tests, including the actophotometer, rotarod, open field, beam walk, gait evaluation, ability to grip, and catalepsy bar tests. Furthermore, the brain dopamine level was then estimated for the extracted tissues. Also, through molecular docking, the binding effectiveness of plumbagin was assessed for human MAO-B. After that, plumbagin was put through 100 ns of molecular dynamic simulations to examine the stability of its conformational binding to the target protein. Furthermore, ADMET tests were used to verify Plumbagin's druggability.

Results: Plumbagin was found to alleviate rotenone-induced motor abnormalities and restore brain dopamine levels. Furthermore, plumbagin showed excellent interactions with MAO-B (monoamine oxidase-B) when compared with selegiline (a standard drug for Parkinson's disease).

Conclusion: These findings underscore the potential therapeutic efficacy of plumbagin in mitigating behavioural deficits in rotenone-induced rodents. Considering this, plumbagin might be a feasible pharmacological strategy for the control of rotenone-triggered behavioural impairment in rats (in vivo), and it might display interesting interactions with MAO-B (in silico).

Plumbagin 对中毒啮齿动物运动障碍的治疗作用
背景:帕金森病是一种以黑质内多巴胺神经元逐渐减少为特征的疾病,最终导致多巴胺缺乏,进一步引起行动和认知障碍。在悠久的传统中,一系列传统中药(TCM)已通过测试,并被用于避免神经退行性疾病。中国临床上使用的一种名为白花丹或板蓝根的药物,其主要活性成分就是板蓝根苷:本研究探讨了通过皮下注射鱼藤酮诱导的帕金森病大鼠模型的改变:雄性大鼠皮下注射1.5 mg/kg剂量的鱼藤酮,然后口服不同剂量的普鲁卡因(10、20和40 mg/kg)。大鼠接受了各种运动能力测试,包括动觉光度计、转体、空场、横梁行走、步态评估、抓握能力和催眠棒测试。此外,还对提取的组织进行了脑多巴胺水平估算。同时,通过分子对接,评估了 plumbagin 与人类 MAO-B 的结合效果。随后,对 plumbagin 进行了 100 ns 的分子动力学模拟,以检验其与目标蛋白构象结合的稳定性。此外,还采用了ADMET测试来验证Plumbagin的可药性:结果:研究发现,Plumbagin能缓解鱼藤酮诱导的运动异常,并恢复大脑多巴胺水平。此外,与西格列汀(一种治疗帕金森病的标准药物)相比,Plumbagin 与 MAO-B(单胺氧化酶-B)之间的相互作用非常出色:结论:这些研究结果表明,Plumbagin 在减轻鱼藤酮诱导的啮齿动物的行为障碍方面具有潜在疗效。有鉴于此,Plumbagin可能是控制鱼藤酮诱发的大鼠行为障碍(体内)的一种可行的药理学策略,而且它可能与MAO-B发生有趣的相互作用(体内)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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