A Polygonatum-Based Functional Formula Improves Stress-Induced Depressive-like Behaviors via Modulation of Neuroinflammation and Tryptophan Metabolism

TL;DR

A functional formula based on Polygonatum sibiricum reduces stress-induced depression in mice by reducing neuroinflammation and balancing tryptophan metabolism.

Contribution

This study identifies a novel functional food formula that modulates neuroinflammation and tryptophan metabolism to alleviate stress-induced depressive behaviors.

Findings

PSF reduced depressive-like behaviors and inhibited NLRP3–caspase-1–GSDMD-mediated pyroptosis in stressed mice.

PSF restored tryptophan metabolism toward serotonin production and stabilized neurotransmitter homeostasis.

PSF partially reversed stress-induced gut microbiota dysbiosis and protected hippocampal neurons.

Abstract

Depression-related mood disturbances are increasingly recognized as nutrition-sensitive conditions associated with chronic stress-induced neuroinflammation and metabolic imbalance. Polygonatum sibiricum, Poria cocos, Lilium brownii, and Radix Glycyrrhizae Preparata are edible medicinal plants commonly used in functional foods. In this study, we evaluated the antidepressant effects of a Polygonatum sibiricum-based functional formula (PSF) in a chronic restraint stress (CRS) mouse model. CRS induced prominent anhedonia and behavioral despair, accompanied by microglial overactivation, activation of the NLRP3 inflammasome, and dysregulated tryptophan metabolism. PSF supplementation significantly alleviated depressive-like behaviors and inhibited NLRP3–caspase-1–GSDMD-mediated pyroptosis, leading to reduced hippocampal IL-1β and IL-18 levels. Importantly, PSF restored tryptophan metabolism toward serotonin production, stabilized monoaminergic and glutamate/GABA neurotransmission, and protected hippocampal neurons. Moreover, PSF partially reversed stress-induced gut microbiota dysbiosis. Collectively, these results demonstrate that PSF acts as a neuroimmune–metabolic modulator that improves mood-related behaviors by regulating inflammatory signaling, tryptophan metabolism, and neurotransmitter homeostasis, supporting its potential development as a functional food intervention for stress-induced depression.

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