Major depressive disorder (MDD) is a complex psychiatric condition with diverse etiological factors. Typical pathological features include decreased cerebral cortex, subcortical structures, and grey matter volumes, as well as monoamine transmitter dysregulation. Although medications exist to treat MDD, unmet needs persist due to limited efficacy, induced side effects, and relapse upon drug withdrawal. Polysaccharides offer promising new therapies for MDD, demonstrating antidepressant effects with minimal side effects and multiple targets. These include neurotransmitter, neurotrophin, neuroinflammation, hypothalamic-pituitary-adrenal axis, mitochondrial function, oxidative stress, and intestinal flora regulation. This review explores the latest advancements in understanding the pharmacological actions and mechanisms of polysaccharides in treating major depression. We discuss the impact of polysaccharides' diverse structures and properties on their pharmacological actions, aiming to inspire new research directions and facilitate the discovery of novel anti-depressive drugs.
Keywords: Major depressive disorder; Microbial gut-brain axis; Mitochondrial dysfunction; Neuroinflammation; Neurotrophins; Polysaccharide.
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