Anti-Alzheimer's Disease Target and Beneficial Effect in Formononetin

Introduction: Alzheimer's Disease (AD), a common neurodegenerative relevance of dementia, is spreading in the world. Hitherto, the pharmacological treatment for AD is prescribed limitedly in clinical application. Recently, it has been found that naturally occurring extracts possess promising anti-neurodegenerative properties, including AD. Methods: Our previous study indicated that formononetin (FMN) exerts the anti-AD benefits based on bioinformatics analysis. However, the experimental validation for bioinformatics findings has not been conducted. In this study, we primarily applied the molecule docking analysis to ascertain the pharmacological targets, including cytochrome P450 19A1 (CYP19A1). Transgenic AD mice were used to validate the bioinformatics findings in vivo experimentally. Molecular docking data showed that FMN acted directly on CYP19A1 target protein with effective binding sites and potent combining affinity/energy. Results: Meanwhile, FMN intervention contributed to an increased trend of body weight in transgenic AD mice reduced hippocampal expression of Aβ1-42, and elevated content of CYP19A1. Additionally, FMN intervention showed reduced terminal deoxynucleotidyl Transferase dUTP Nick-End Labeling (TUNEL) expression and increased CYP19A1 and Ki67 expressions in hippocampal sections of transgenic AD mice. Conclusion: Collectively, FMN may be used for the prevention of AD, and the pharmacological activities are possibly related to reducing Aβ1-42, and TUNEL expressions to increase Ki67 and CYP19A1 activities.