NEUROPROTECTIVE EFFECT OF LINALOOL IN CHRONIC UNPREDICTABLE STRESS-INDUCED COGNITIVE IMPAIRMENT - IN SILICO AND IN VIVO STUDIES

Abstract

The growing prevalence of stress-induced cognitive impairment is becoming a significant concern, although the precise mechanism is still not fully understood. The chronic unpredictable stress (CUS) model is widely used to study stress-induced cognitive impairment, as it correlates with cognitive decline, behavioral changes, and abnormal cortisol levels in humans. Linalool, known for its traditional use in alleviating anxiety, acting as an antidepressant, sedative, and neuroprotective agent, was investigated in this study. The research explored the genes involved in stress-induced cognitive impairment through network pharmacology, molecular docking, and in vivo methods to assess linalool's neuroprotective effects. The study identified PTGS2, GSK3B, MAPK1, JAK2, PARP1, KDR, NR3C1, MDM2, PRKCA, and MAPK8 as key targets for therapeutic activity in CUS and a strong docking score with PTGS2. The network analysis revealed that neuroprotective effects of linalool have been associated with its modulation of neurodegeneration and sphingolipid signaling pathways, indicating that linalool may inhibit these pathways. The in vivo findings showed that Linalool ameliorated the chronic stress induced behavioral changes, reduced the acetylcholinesterase levels in the brain and corticosterone levels in blood. Both in vitro and in vivo studies indicate that linalool possesses neuroprotective properties and could be a potential target for treating cognitive impairment.