Cordyceps militaris and Armillaria mellea formula alleviates depressive behaviors via microglia regulation in an unpredictable chronic mild stress animal model

Summary

Two medicinal mushrooms, Cordyceps militaris and Armillaria mellea, when combined as a formula, can help reduce depression-like symptoms in stressed animals. The formula works by balancing immune cells in the brain called microglia and restoring normal chemical messenger function. This treatment shows promise as a natural alternative to conventional antidepressants with fewer side effects.

Background

Major Depressive Disorder (MDD) is a significant mental health condition affecting millions worldwide. While Cordyceps militaris (CM) and Armillaria mellea (AM) are medicinal mushrooms with anti-inflammatory properties and potential antidepressant effects, limited knowledge exists about their combined efficacy and mechanisms involving microglia modulation.

Objective

To investigate whether a combined CM-AM formula exhibits antidepressant-like effects in an unpredictable chronic mild stress (UCMS) animal model and to clarify the mechanism by which the formula modulates activated microglia.

Results

The CM-AM formula effectively prevented UCMS-induced depression-like behaviors including anhedonia and hypoactivity, normalized monoamine turnover rates in the prefrontal cortex and hippocampus, and decreased elevated serum corticosterone levels. The formula alleviated stress-induced microglia activation by downregulating pro-inflammatory proteins and upregulating anti-inflammatory proteins while balancing M1 and M2 microglia populations.

Conclusion

The CM-AM formula demonstrates antidepressant-like effects through neurotransmitter regulation and immunomodulation, suggesting potential as a complementary and alternative therapy for depression management.
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