Talib Mohd, Siddiqui Nazia, Tripathi Prabhash Nath, Chaudhary Ankit
Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, Meerut, 250005, India.
Department of Pharmacy, Meerut Institute of Technology, Meerut, 250005, India.
Neurochem Res. 2025 Aug 13;50(4):258. doi: 10.1007/s11064-025-04516-6.
Alzheimer's disease (AD) is the utmost age-linked neuro-degenerative conditions, marked via gradual deterioration of cognitive abilities and continues to be a significant worldwide health issue. Etiology of AD is linked to neurobehavioral variations, deposition of Aβ, p-Tau, activations of glycogen synthase kinase-3 (GSK-3β), and fluctuations in cyclic nucleotides including cAMP & cGMP. As per evidence, PDE-5 inhibitors are able to boost cAMP & cGMP levels and other etiological hallmarks, which could be a novel AD cure. The main objective of present study was to examine therapeutic potential of Avanafil in a rat model of AD induced by administering 60 mg/kg of D-galactose (D-galac) and 10 mg/kg of Aluminium chloride (AlCl) for a period of 42 days. Following this, 28 days of therapy with two different doses of Avanafil (3 mg/kg and 6 mg/kg) was given. Towards end of treatment, locomotor activity & Morris water maze were performed. Rats were then euthanized and hippocampus was isolated for biochemical parameters & histological investigation. Results revealed that both neurobehavioral parameters exhibits significant difference in treatment group as compared to toxic group. Alterations in level of AchE, Aβ (1-42), GSK-3β, p-Tau, tumor necrosis factor- alpha (TNF-α), IL-1β, & IL-6, cAMP, cGMP & BDNF, and oxidative stress were significantly reversed towards normal level in the treatment group when compared to toxic rats. Histopathological changes by H&E staining showed significant difference in treatment vs. toxic rats. The current investigation suggested that Avanafil improves memory by improving cAMP and cGMP pathways, implying that it may have therapeutic prospective in cognitive deficiencies linked with Alzheimer's disease.
阿尔茨海默病（AD）是最常见的与年龄相关的神经退行性疾病，其特征是认知能力逐渐衰退，并且仍然是一个重大的全球健康问题。AD的病因与神经行为变化、β淀粉样蛋白（Aβ）沉积、磷酸化tau蛋白（p-Tau）、糖原合酶激酶-3（GSK-3β）激活以及包括环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）在内的环核苷酸波动有关。根据现有证据，磷酸二酯酶5（PDE-5）抑制剂能够提高cAMP和cGMP水平以及其他病因学特征，这可能是一种新型的AD治疗方法。本研究的主要目的是在通过给予60mg/kg D-半乳糖（D-galac）和10mg/kg氯化铝（AlCl）诱导42天的AD大鼠模型中，研究阿伐那非的治疗潜力。在此之后，给予两种不同剂量（3mg/kg和6mg/kg）的阿伐那非进行28天的治疗。在治疗结束时，进行运动活动测试和莫里斯水迷宫实验。然后对大鼠实施安乐死，并分离海马体进行生化参数测定和组织学研究。结果显示，与中毒组相比，治疗组的两个神经行为参数均表现出显著差异。与中毒大鼠相比，治疗组中乙酰胆碱酯酶（AchE）、Aβ（1-42）、GSK-3β、p-Tau、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、cAMP、cGMP和脑源性神经营养因子（BDNF）水平的变化以及氧化应激均显著恢复至正常水平。苏木精-伊红（H&E）染色显示，治疗组与中毒大鼠的组织病理学变化存在显著差异。当前研究表明，阿伐那非通过改善cAMP和cGMP途径来改善记忆，这意味着它在与阿尔茨海默病相关的认知缺陷方面可能具有治疗前景。
