Abstract
Background/Objectives: Chronic stress disrupts neurochemical balance, triggers inflammation, and compromises neuronal integrity, contributing to the development of stress-related disorders. This study aimed to evaluate the preventative effects of Tremella fuciformis Berk (TF) enzymatic extracts on chronic restraint stress (CRS)-induced behavioral, neurochemical, and inflammatory dysfunctions in mice. Methods: Male C57BL/6N mice were administered TF at doses of 50 mg/kg and 100 mg/kg daily via oral gavage for 21 days during CRS exposure. Behavioral assessments, including anxiety and depression-like behavior tests, were conducted. Neurochemical and inflammatory markers were analyzed using PCR and ELISA, while histological examinations of hippocampal regions were performed to assess neuronal integrity. In vitro assays evaluated neuronal cell viability, protection against corticosterone (CORT)-induced cytotoxicity, and inhibition of monoamine oxidase (MAO) activity. Results: TF supplementation alleviated CRS-induced weight loss, normalized serum CORT levels, increased locomotor activity, reduced immobility time, and decreased anxiety-like behaviors. TF upregulated brain-derived neurotrophic factor (BDNF) mRNA, downregulated pro-inflammatory markers (CXCL2, iNOS, IFNG), and mitigated neuronal apoptosis in the hippocampus. In vitro, TF improved neuronal cell viability, protected against CORT-induced cytotoxicity, and significantly inhibited MAO activity, particularly MAO-A. Conclusions: These findings demonstrate the neuroprotective and anti-stress effects of Tremella fuciformis Berk enzymatic extracts, supporting its potential as a natural therapeutic intervention for stress-related disorders.