Cydonia oblonga Mill. fruit extract attenuates depressive-like behaviors in a mouse model of breast tumor via regulating oxidative stress, inflammation, and gut microbiota

Cydonia oblonga Mill. is a flavonoid-rich fruit and has potential applications in functional or nutritional foods. Herein, we examined the effects of hydroethanolic extract of Cydonia oblonga Mill. fruit (HECO, 600 mg/kg) on depressive-like behaviors in a mouse model of breast tumor. Flavonoids in HECO were determined by Ultra-Performance Liquid Chromatography-Mass Spectrometry. Depressive-like behaviors and hippocampal oxidative stress markers and inflammatory cytokines were measured. Colonic contents were collected for 16S rRNA sequencing. HECO was enriched with rutin, L-epicatechin, catechin and other flavonoids and significantly increased the time spent in the center of the open-field test and sucrose water consumption, and decreased immobility time in the tail suspension test without significant effect on tumor growth. HECO significantly increased hippocampal 5-hydroxytryptamine, brain-derived neurotrophic factor levels, glutathione peroxidase and superoxide dismutase activities, decreased hippocampal interleukin-6, interleukine-1β, tumor necrosis factor-α and malondialdehyde levels. In addition, HECO increased diversity of gut microbiota and improved intestinal barrier integrity. This study suggests that HECO is a potential candidate for breast cancer-related depression by regulating gut microbiota and inhibiting hippocampal oxidative stress and inflammation. • The ethanol extract of Cydonia oblonga Mill. improved breast tumor-induced depression. • The extract elevated hippocampal antioxidant enzymes to lower malondialdehyde levels. • The extract increased gut microbiota diversity and reduced hippocampal inflammation. • The extract treatment enriched KEGG pathways, including glutathione metabolism.