Arbutin ameliorated depression by inhibiting neuroinflammation and modulating intestinal flora.

BACKGROUNDArbutin (AR), a natural glycoside compound widely distributed in botanical sources, exerts neuroprotective properties. Nevertheless, the pharmacological effect of AR on depression and its underlying mechanism remain undefined.

METHODSThe mice were induced by chronic unpredictable mild stress (CUMS) procedure 16S rRNA sequencing and metabolomic analyses were conducted. The in vitro neuroinflammatory model was established using lipopolysaccharide (LPS) stimulated BV2 microglia.

RESULTSThe present study found that AR alleviated the depressive-like behaviors, inflammatory reaction, oxidative stress, restored neurotrophic factors and gut tight junction proteins. TLR4/NF-κB/IRAK1 signaling was involved in these alterations. 16S rRNA sequencing and metabolomics showed that AR enriched muribaculaceae and tryptophan metabolism. Muribaculum intestinale and AR ameliorated depressive-like behaviors, inflammation and 5-HT content, Tryptophan Hydroxylase 1 (TPH1) and Indoleamine 2,3-Dioxygenase 1 (IDO1) expressions, tryptophan metabolism and kynurenine route. The molecular docking and molecular dynamic suggested that AR might bind to TPH1 and IDO1.

CONCLUSIONIn conclusion, AR alleviated depressive-like behavior in mice by reducing neuroinflammation, modulating gut microbiota, and TPH1/IDO1-mediated serotonin synthesis.