Antidepressant-like and neuroprotective effects of pine needle extracts: evidence from behavioral, transcriptomic, and biochemical studies.

Neuroinflammation is a key characteristic associated with neurological disorders, particularly depression and anxiety. This study aims to evaluate the neuroprotective and antidepressant-like effects of pine needle (PN) extracts in an LPS-induced neuroinflammation mouse model. Following seven days of oral administration of PN, the tail suspension test demonstrated a significant reduction in immobility time in PN-treated mice compared to LPS controls, surpassing the effect of the standard antidepressant bupropion. To elucidate the underlying mechanisms, we conducted a whole-genome microarray analysis. This analysis highlighted pathways related to neuroprotection, synaptic plasticity, and pro-inflammatory cytokine regulation, with a notable enrichment in the Apelin signaling pathway. Quantitative PCR analysis revealed that PN treatment increased the levels of Apelin and its receptor while decreasing proinflammatory cytokines Tnfa and IL1b in the hippocampus. ELISA further demonstrated elevated levels of key neurotransmitters, including dopamine and noradrenaline, in the mouse hippocampus. Additionally, we performed GC/MS analysis to identify bioactive compounds in PN, revealing D-Pinitol and Shikimic acid as major constituents. Importantly, catechol exhibited significant neuroprotective effects, and similar protective effects were also noted in the mixed compositions. The MTT assay showed that PN and its compounds significantly improved cell metabolic activity against dexamethasone-induced cytotoxicity. In conclusion, our findings highlight the potential of PN as a natural therapeutic agent for depressive symptoms, promoting neuroprotection, enhancing neurotransmitter levels, and modulating inflammatory responses. See also the graphical abstract(Fig. 1).