Nazir Samra, Anwar Fareeha, Saleem Uzma, Ahmad Bashir, Raza Zohaib, Sanawar Maham, Rehman Artta Ur, Ismail Tariq
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, 54000, Pakistan.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan.
Neurochem Res. 2021 Jul;46(7):1814-1829. doi: 10.1007/s11064-021-03327-9. Epub 2021 Apr 20.
Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with decline in memory and cognitive impairments. Phosphodiesterase IV (PDE4) protein, an intracellular cAMP levels regulator, when inhibited act as potent neuroprotective agents by virtue of ceasing the activity of Pro-inflammatory mediators. The complexity of AD etiology has ever since compelled the researchers to discover multifunctional compounds to combat the AD and neurodegeneration. The aim of this study was to probe into role of drotaverine a PDE4 inhibitor in the management of AD. Albino mice were divided into seven groups (n = 10). Group 1 control group received carboxy methyl cellulose (CMC 1 mL/kg), group II diseased group treated with streptozotocin (STZ 3 mg/kg) by intracerebroventricular (ICV) route, group III administered standard drug Piracetam 200 mg/kg and groups IV-VII were given drotaverine (10, 20, 40, and 80 mg/kg i/p respectively). Groups II-VII were given STZ (3 mg/kg, ICV) on 1st and 3rd day of treatment to induce AD. All the groups were given their respective treatments for 23 days. Improvement in learning and memory was evaluated by using behavioral tests like open field test, elevated plus maze test, Morris water maze test and passive avoidance test. Furthermore, brain levels of biochemical markers of oxidative stress, neurotransmitters, β-amyloid and tau protein were also measured. Drotaverine showed statistically significant dose dependent improvement in behavioral and biochemical markers of AD: the maximum response was achieved at a dose level of 80 mg/kg. The Study concluded that drotaverine ameliorates cognitive impairment and as well as exhibited modulated the brain levels of neurotransmitters.
阿尔茨海默病（AD）是一种与记忆力减退和认知障碍相关的进行性神经退行性疾病。磷酸二酯酶IV（PDE4）蛋白作为细胞内cAMP水平的调节剂，受到抑制时，通过停止促炎介质的活性而起到强大的神经保护作用。自那时以来，AD病因的复杂性促使研究人员去发现多功能化合物来对抗AD和神经退行性变。本研究的目的是探究PDE4抑制剂屈他维林在AD治疗中的作用。将白化小鼠分为七组（n = 10）。第1组为对照组，给予羧甲基纤维素（CMC 1 mL/kg）；第II组为患病组，通过脑室内（ICV）途径注射链脲佐菌素（STZ 3 mg/kg）；第III组给予标准药物吡拉西坦200 mg/kg；第IV - VII组分别给予屈他维林（10、20、40和80 mg/kg，腹腔注射）。在治疗的第1天和第3天，第II - VII组给予STZ（3 mg/kg，ICV）以诱导AD。所有组均接受各自的治疗23天。通过旷场试验、高架十字迷宫试验、莫里斯水迷宫试验和被动回避试验等行为测试评估学习和记忆的改善情况。此外，还测量了氧化应激、神经递质、β-淀粉样蛋白和tau蛋白等脑生化标志物的水平。屈他维林在AD的行为和生化标志物方面显示出具有统计学意义的剂量依赖性改善：在80 mg/kg的剂量水平达到最大反应。该研究得出结论，屈他维林可改善认知障碍，并调节脑内神经递质水平。
