Antidepressant and neuroprotective potential of stingless bee honey in a preclinical stress model

Stingless bee honey (SBH), as a functional food supplement, is of particular interest in this context due to its potential to modulate neurobiological factors such as BDNF and neurotransmitter release, which are often disrupted in depressive disorders. SBH is a fermented honey rich in trehalulose, probiotics, organic acids including aliphatic acids, and various bioactive compounds. These properties mitigate neurodegenerative processes by reducing oxidative stress and inflammation, enhancing neuronal resilience, and supporting the maintenance of cognitive function and overall brain health. This preclinical study aims to investigate the antidepressant effects of SBH in the chronic restrained stress (CRS) depression model via behavioural, hormone secretions, and histological analyses. Forty-two Swiss Albino mice (8 weeks old) were divided into five groups, receiving SBH supplementation or paroxetine (positive control). CRS was induced for 2 h daily for 28 days. The evaluated effects include body weight, behavioural tests, neurotransmitter levels, hippocampal neuron integrity, and brain-derived neurotrophic factor (BDNF) expression. The results of the physicochemical analysis confirmed that the SBH complied with the Malaysian Standard (MS2683:2017). FESEM experiment indicates the presence of bacteria and yeast on the walls of cerumen pots. Behavioural assessments demonstrated a significant reduction in anxiety-like behaviours and immobility duration among SBH-treated groups, indicative of its anxiolytic and antidepressant-like effects. The biochemical evaluations via ELISA assay showed that SBH supplementation reduced corticosterone levels, maintained serotonin concentrations, and increased dopamine availability, whilst elevating the serum phenylalanine levels. Upregulated BDNF expression and downregulation of the pro-inflammatory cytokines were also observed. The increased level of BDNF has been closely linked with synaptic plasticity as well as regulating the monoaminergic neurotransmitter regulation. These findings underscore the potential of SBH as a neuroprotective supplement, likely mediated by monoamine modulation, neurogenesis, and anti-inflammatory effects, warranting further clinical investigations as a functional food with anti-depressant effects. • We investigated the neuroprotective and inflammatory effects of stingless bee honey (SBH) in an induced-chronic restraint stress (CRS) model. • SBH is fermented honey that is rich in probiotics including those derived from the surface walls of propolis, exerting higher antioxidant properties. • SBH supplementation exhibited improved cognitive functions via behavioural patterns, modulating neuroinflammatory markers alongside mitigating neuronal damage in CA3 and DG regions of hippocampal tissues. • Current findings highlighted SBH as a potential natural therapy and prevention for stress-induced cognitive decline, particularly depression disorder.