Black mulberry anthocyanins induce antidepressant-like effects via the BDNF/TrkB signaling pathway

Abstract

Depression is a widespread mental health condition associated with impaired neuroplasticity and disrupted brain-derived neurotrophic factor (BDNF)/TrkB signaling. Black mulberry, rich in anthocyanins, shows promise as a natural intervention for its anti-oxidative and anti-inflammatory profiles. This study evaluated the antidepressant-like effects of black mulberry anthocyanins in mice subjected to chronic mild stress (CMS). Black mulberry anthocyanins, which were extracted and quantified, were orally administered at 250 mg kg⁻¹ daily for four weeks, followed by behavioral assessments including sucrose preference and open field and forced swimming tests. Our results indicated that black mulberry treatment improved depressive behaviors and reduced serum corticosterone. The RNA sequencing analysis in the hippocampal tissues indicated that black mulberry modulated genes involved in synaptic function and mood regulation, especially BDNF expression. The immunofluorescence assay indicated that black mulberry restored hippocampal BDNF levels. Furthermore, K252a pretreatment not only abolished the antidepressant-like effects of black mulberry, but also blocked the role of black mulberry in synaptic proteins, neurogenesis and synaptogenesis. In conclusion, black mulberry shows potential as a dietary-based intervention for managing stress-related disorders by enhancing BDNF/TrkB signaling, supporting its therapeutic value as a functional food for mental health.