Ameliorative Role of Phosphodiesterase-5 (PDE-5) Inhibitor “Avanafil” via Modulating cAMP & cGMP Pathway Against Alzheimer’s Disease

Abstract

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 (AlCl₃) 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.