The role of CCR5 in the protective effect of Esculin on lipopolysaccharide-induced depressive symptom in mice

ABSTRACT Background The purpose of this study was to evaluate whether Esculin could improve the depressive symptom induced by LPS in mice and explore the role of CCR5 in its potential mechanism. Methods Mice were stimulated with LPS to establish depression model and treated with Esculin. The emotional alteration was assessed via behaviour tests. The ELISA assay and western blot analysis were applied to detect the expressions of inflammatory cytokines and correlative proteins. Results As a result, Esculin played a protective role in LPS-induced depressive dysfunction, which was possible through the reduction of M1 microglia, and elevation of M2 microglia by inhibiting TLR4/NF-κB signaling pathway regulated by CCR5. Besides, Esculin led to up-regulation of the CREB/BDNF neuroprotective pathway, and suppression of inflammatory cytokines both in the central and peripheral system. BV2 cells were stimulated with LPS to further elucidate the accordant mechanism in vitro. Molecular docking results suggested that Esc bound to CCR5 at amino acid residues TYR187 and THR105 through hydrogen-bonding. Limitations Transgenic animals might be useful for the further investigation. Conclusions From the overall results, we concluded that Esculin might exert a beneficial effect on LPS-induced depression in mice and represent an effective treatment for depression.