Antidepressant Neuroprotective Mechanisms of Natural Products in Depression Management: A Comprehensive Review

Depression is a complex psychiatric disorder with significant global impact. While conventional antidepressants remain the mainstay of treatment, their limitations-such as delayed onset, limited efficacy, and adverse effects-highlight the need for novel approaches. Recent advances include psychedelic-assisted therapy, ketamine infusions, AI-guided precision psychiatry, and neuromodulation techniques, offering more personalized and rapid interventions. Concurrently, Natural Products (NPs) have gained attention for their multi-target neuroprotective effects. Derived from botanical and ethnomedical sources, compounds like apigenin, resveratrol, baicalin, and curcumin modulate neuroinflammation, oxidative stress, neurotransmitter balance, and neuroplasticity. Despite promising preclinical data, challenges such as poor bioavailability, variability in composition, and limited clinical validation hinder their integration into mainstream care. This review explores the evolving landscape of depression management, emphasizing the therapeutic potential and translational challenges of NPs as adjunct or alternative treatments in addressing unmet clinical needs.