ALOPERINE SUPPRESSES NEUROINFLAMMATION AND DEPRESSIVE-LIKE BEHAVIOR VIA TLR4/NF-ΚB INHIBITION

Abstract

The present study provides the first evidence that aloperine exerts significant antidepressant-like effects in a lipopolysaccharide-induced model of depression, primarily through modulation of insilico and molecular neuroinflammatory pathways. LPS administration reliably induced depressive-like behavior, characterized by increased immobility and reduced struggling time in the Forced Swim Test, consistent with activation of innate immune responses via TLR4 signaling. This activation promotes NF-κB translocation and subsequent release of pro-inflammatory cytokines, contributing to neuroinflammation and behavioral deficits. The observed upregulation of TLR4 and NF-κB expression in the LPS group aligns with established mechanisms linking inflammation to depression. Treatment with aloperine significantly attenuated both behavioral impairments and molecular alterations induced by LPS, suggesting its potential role in suppressing neuroinflammatory signaling. These findings are supported by previous evidence demonstrating that aloperine inhibits TLR4/NF-κB-mediated inflammatory responses. Comparable effects have been reported with other anti-inflammatory agents, further emphasizing the importance of targeting inflammatory pathways in depression. Additionally, fluoxetine demonstrated similar protective effects, reinforcing the concept that antidepressants may exert therapeutic benefits partly through anti-inflammatory mechanisms. Despite these promising findings, limitations include the lack of assessment of downstream cytokines and neuroplasticity-related markers, which warrant further investigation. Overall, the study highlights aloperine as a potential therapeutic candidate for inflammation-associated depression by modulating key neuroinflammatory mediators.