Brain regional pharmacokinetics of hydroxytyrosol and its molecular mechanism against depression assessed by multi-omics approaches

•Hydroxytyrosol (HT) was highly distributed in the hippocampus of brain.•Increased blood–brain barrier permeability of depressive mice promotes the brain uptake of HT.•The specific brain distribution of HT could support its bioactivities related to hippocampus.•HT improved fatty acids disturbances in the hippocampus with region-specific responses.•HT inhibited the hippocampal C3–CD11b pathway for microglia activation with region-specific characteristics.