The Ganoderma lucidum and Rosa roxburghii formulation prevents depressive-like behaviors.
TheandTratt Formulation Prevents Depressive-like Behaviors in Mice by Modulating Tryptophan Metabolism via the Gut-Brain Axis and Upregulating the BDNF/TrkB/PI3K/AKT Pathway.
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Key Findings
Abstract
Depression is a common mental disorder that substantially impairs patients' daily life and work. To identify natural and safe preventive options, we investigated the preventive effect and underlying mechanism of theandTratt formula (GLRRTF) on depression. A total of 72 chemical components in GLRRTF were identified by UHPLC-ESI-Q-Exactive Plus Orbitrap-MS Analysis. GLRRTF (containing 400 mg/kg ofextract and 800 mg/kg ofextract per day), administered as a 1-week preventive intervention followed by 4 weeks of co-administration with chronic unpredictable mild stress, prevented the development of depression-like behaviors in male C57BL/6J mice and reduced neuronal damage in the hippocampus. Airflow-assisted desorption electrospray ionization mass spectrometry imaging and enzyme-linked immunosorbent assays showed that GLRRTF corrected abnormalities in neurotransmitter levels. The 16S rRNA sequencing indicated that GLRRTF restored dysbiosis of the gut microbiota. Metabolomic profiling revealed that GLRRTF increased the level of tryptophan and promoted tryptophan metabolism towards the 5-HT and indole pathways in feces and the brain. Western blot demonstrated that GLRRTF increased 5-HT production from tryptophan in the brain by regulating tryptophan hydroxylase 2 and DOPA decarboxylase. GLRRTF activated the PI3K/AKT pathway by regulating brain-derived neurotrophic factor and its receptor tropomyosin receptor kinase B. This research provides a comprehensive mechanistic understanding of GLRRTF's preventive effect against depression, highlighting its potential as a novel, safe, and preventive functional food formulation.
Affiliation
Fangling Feng
External References
- PubMed ID:
- 42121478
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