Targeting Central Nervous System (CNS) diseases with bioactive compounds using network pharmacology and screening tools

Abstract

Today we hear and see the increase in Parkinson disease, which have become among the most common diseases in the world. Therefore, we targeted some proteins that are related to the disease. Our goal in this study is to inhibit all of the A2AA-R, GABA-A, NrF2, and αsynuclein. After examining various plants from Chlef in Algeria, we selected salvia officinalis and curcuma longa. After that, we made the extraction of curcuma longa with ethanol, and we had obtained good yield. Our In Silico study demonstrated that there is an inhibitory combination of the bisdemethoxycurcumin compound with A2AA-R,with a binding capacity estimated at ∆G = -9.1 kcal/mol, and the ar-turmerone compound with the A2AA-R with a binding capacity estimated at ∆G = -8.6 kcal/mol. α -turmerone had make a cohesion with NrF2 with energy estimated at ∆G=-7.4kcal/mol. Consequently, makes the bisdemethoxycurcumin-A2AA-R interaction (ΔG = -9.1 kcal/mol) demonstrates the strongest binding affinity among the tested compounds. Our QSAR study approach was based on using two methods, multiple linear regression (MLR), support vector regression (SVR). SVR demonstrated superior predictive accuracy (Q² = 0.992, R² train = 0.989) compared to MLR (Q² = 0.559, R² train = 0.766). After the comparison between bisdemethoxycurcumin and l-dopa , our findings suggest bisdemethoxycurcumin (BDMC) offers dual benefits comparable binding affinity to key targets (∆G = -9.1 kcal/mol) while additionally addressing PD's core pathologies through antioxidant and anti-inflammatory mechanisms. This multifunctional activity positions BDMC as a potential disease-modifying adjunct to conventional therapy.