A Systems Biology Approach to Understanding Delirium Pathophysiology and Identifying Natural Compounds for Potential Therapeutic Purposes

Delirium is an acute neurocognitive disorder marked by disruptions in attention, cognition, and awareness, particularly prevalent among older and critically ill patients. This study applies a systems biology framework to dissect the molecular underpinnings of delirium and evaluate natural compounds for potential therapeutic roles. Through bioinformatics analyses, key biomarkers related to delirium, including IL6, AKT1, JUN, APP, and PPARGC1A, were identified, implicating pathways tied to neuroinflammation, oxidative stress, and synaptic function. Traditional Chinese medicine (TCM) compounds were mapped to these biomarkers, revealing candidates that may modulate inflammatory and metabolic processes central to delirium. The study highlights the potential of compounds like melatonin, dehydroepiandrosterone (DHEA), resveratrol, progesterone, and paclitaxel to provide multi-targeted approaches for delirium management. Findings underscore the role of integrating natural compounds with conventional treatment to address delirium's complex pathophysiology. This research offers new insights into delirium's molecular landscape and introduces avenues for novel, natural compound-based therapeutic interventions.