Alzheimer’s Disease (AD) characterized by memory impairment, aphasia, personality changes and other recognition dementia symptoms, is a kind of neurodegenerative disease with a high incidence among the aged [1, 2]. Several scientists shed light on the etiology of AD, investigating the pharmacological mechanism of potential drugs for AD treatment. So far, many factors have been found contributed to the morbidity of AD, concluding the insufficiency of acetylcholine (Ach), aggregation of β-amyloid (Aβ) peptides, phosphorylation of Tau Protein and so on [3–8]. However, no pharmacological mechanism was found to be well-recognized. Donepezil and Memantine Hydrochloride, respectively representing acetylcholine esterase inhibitors(AchEI) and N-methyl-D-aspartic acid receptor (NMDAR) antagonists, are commonly utilized for the treatment of AD, but they also have some side effects, such as dizziness, nausea, and vomiting [9]. Many potential drugs for AD treatment were withdrawn in the period of clinical trials because of severe side effects [10]. It is still of great necessity to develop new drugs for the treatment of AD.
According to the available literatures, the phosphodiesterase 4 (PDE4) subtype could be a potential target for the treatment of AD, mainly by inhibiting the aggression of Aβ and nourishing the brain environment [11–16]. A series of phthalazinone derivatives were synthetized by Irene G. Salado’s team, and these compounds are effective to the treatment of Human African trypanosomiasis through the inhibition of PDE4 [17]. From the other perspectives, these compounds might be effective for the treatment of AD. What’s more, phthalazinone derivatives have been studied as structure correctors to interfere with the structural composition of Apolipoprotein E4 (apo E4) in cultured neurons, which as a result, protect the neurons from Tau hyperphosphorylation, Aβ deposition [18]. Besides, the phthalazine derivatives have been applied to neuron cells or animal behavioral experiments to investigate their potential in AD treatment. The results available all shown that the phthalazine had the potency to cure AD by inhibiting AchE, alpha-glycosidase, Cholinesterase (BchE) [19–21]. It is of the great potential that phthalazinone derivatives would be effective in the treatment of AD, or be lead compounds to develop new drugs.
Network Pharmacology integrates chemistry, pharmacology, pharmacodynamics, and facilitates the mechanistic studies of potential drugs [22]. Therefore it is recently popular to be employed to the analysis of potential pharmacological mechanisms of traditional Chinese medicine (TCM) [23, 24]. Yinchenhao decoction, Potentilla Discolor Bunge, Schisandra Chinensis and many other medicinal herbs have been applied to network pharmacology analysis, resulting in potential pharmacological mechanism of herbs to certain disease [25–27]. The core idea of this technology is systematically treating diseases, and this consumption conforms to the actual drug reaction [22]. AD, triggered by multi-targets, would be treated more effectively by the multi-targets drug. It is of great significance to apply network pharmacology analysis to compound bioactivity screening.
In this study, the active compounds would be retrieved from literature with certain bioactivity for PDE4. Only those compounds with certain physical properties would be adopted for analysis. The targets prediction,network construction, and gene enrichment analysis would be conducted from the public database. The underlying pharmacological mechanism of phthalazinone derivatives would be helpful to screen the potential bioactivity and extract compounds to develop drugs for AD treatment.