Rhodomyrtus tomentosa fruit ameliorates LPS induced depression-like behaviors in mice by attenuating hippocampal neuroinflammation via inhibiting the TLR4/MyD88/MAPK/NF-κB/NLRP3 signaling pathway

Introduction Rhodomyrtus tomentosa fruit is a dietary food with various bioactivities. However, the comprehensive mechanisms underlying its antidepressant effects remain be fully understood. Methods This study aimed to assess the effects of the ethanol extract from R. tomentosa (RTEE) on depression-like behaviors in lipopolysaccharide (LPS)-challenged mice, and to explore the molecular basis. Results The results showed that RTEE significantly improved LPS induced depression-like behaviors in mice, as evidenced by increased preference for sucrose in the sucrose preference test, enhanced locomotor activity (elevated total distance, velocity, and center entries) in the open field test, and reduced immobility time in both the tail suspension and forced swim tests. Meanwhile, RTEE significantly increased NeuN + cell numbers and enhanced PSD95 expression in the hippocampus, thus promoting neuronal survival and synaptic plasticity. Additionally, RTEE significantly suppressed microglial and astrocyte activation (indicated by reduced Iba-1 + and GFAP + cell numbers), decreased the expression of hippocampal pro-inflammatory cytokines (TNF-α and IL-6) via inhibiting the TLR4/MyD88/MAPK/NF-κB/NLRP3 signaling pathway, thereby attenuating neuroinflammation. In vitro experiments using microglial BV2 cells showed that RTEE significantly rescued cell viability and reduced NO production via suppressing the NF-κB signaling pathway. Discussion These findings suggested that RTEE improved LPS induced depression-like behaviors in mice by attenuating hippocampal neuroinflammation via inhibiting the TLR4/MyD88/MAPK/NF-κB/NLRP3 signaling pathway. Therefore, this study elucidates the underlying mechanisms through which Rhodomyrtus tomentosa fruit may serve as a novel nutritional intervention for depression.