Abstract
Evodia rutaecarpa (Evodia) is a Chinese herbal medicine with analgesic and anti-neurodegenerative properties. However, whether Evodia compounds can be applied for the comorbid pain of Alzheimer's disease (AD) and the underlying mechanisms remain unclear. Herein, 137 common targets of Evodia between AD and pain were predicted from drug and disease target databases. Subsequently, protein-protein interaction (PPI) network, protein function module construction, and bioinformatics analyses were used to analyze the potential relationship among targets, pathways, and diseases. Evodia could simultaneously treat AD comorbid pain through multi-target, multi-component, and multi-pathway mechanisms, and inflammation was an important common phenotype of AD and pain. The relationship between important transcription factors such as RELA, NF-κB1, SP1, STAT3, and JUN on IL-17, TNF, and MAPK signaling pathways might be potential mechanisms of Evodia. Additionally, 10 candidate compounds were predicted, and evodiamine might be the effective active ingredient of Evodia in treating AD or pain. In summary, this study provided a reference for subsequent research and a novel understanding and direction for the clinical use of evodiamine to treat AD patients with comorbid pain.