Hyperoside ameliorates neuroinflammation associated depression via induced aldehyde dehydrogenase 2 activation: in silico and in vitro insights

Abstract

Depression, a widely observed psychological condition, presents a substantial risk to the general health and welfare of individuals across the globe. Despite the effective therapeutic potential demonstrated by hyperoside against depression, uncertainties persist regarding its precise mechanism of action. The present investigation employed bioinformatics techniques and target prediction strategies to demonstrate that the therapeutic focus of hyperoside in depression lies primarily on ALDH2. Molecular docking and molecular dynamics simulations were utilized to investigate the binding strength and structural characteristics, and simulate the stability of hyperoside's interaction with ALDH2. The results suggest that it has potential as an activator of ALDH2 and may have antidepressant effects by reducing inflammatory factor expression in the hippocampus, similar to the co-crystal compound Alda-1. Moreover, the in vitro experiments demonstrated that hyperoside exerts neuroprotective effects through its anti-inflammatory properties, thereby contributing to its anti-depressant potential. In summary, a multidisciplinary approach was utilized to gather evidence on the potential protective mechanism of hyperoside in depression. This expands the possibilities for its clinical application and indicates its significant theoretical and practical importance. Furthermore, this work presents a comprehensive method for identifying key targets and potential molecular mechanisms in the field of drug discovery.