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Impact of Hericium erinaceus and Ganoderma lucidum metabolites on AhR activation in neuronal HT-22 cells

Summary

This study examined how two medicinal mushrooms, lion’s mane and Reishi, affect nerve cells in the brain. The researchers found that metabolites from these mushrooms don’t harm brain cells and actually boost protective proteins that support cell health and survival. The mushrooms appear to work through a cellular receptor called AhR, which helps facilitate communication between the gut and the brain. These findings suggest that these mushrooms may help support brain function and protect against neurological problems.

Background

The gut microbiota modulates central nervous system development through complex bidirectional interactions. Intestinal microbial metabolites modulate aryl hydrocarbon receptor (AhR) activity, enabling metabolic communication between the host and gut microbiota. Hericium erinaceus and Ganoderma lucidum are medicinal fungi with bioactive compounds that may influence AhR activation.

Objective

To evaluate the effect of H. erinaceus or G. lucidum microbiome cell-free supernatant (M-CFS) with their active metabolites alone and in co-treatment with CAY10464 (AhR antagonist) on metabolic parameters, cell cycle, and protein expression in mouse hippocampal neuronal HT-22 cells.

Results

M-CFS from both fungi showed no cytotoxicity at tested concentrations and did not affect metabolic activity. Treatment increased protein expression of SQSTM/p62, PCNA, c-SRC, SOD1, AhR, Beclin 1, and ERK1/2. AhR played a significant role in the mechanism of action of the tested metabolites, with differential effects between H. erinaceus and G. lucidum.

Conclusion

The M-CFS from H. erinaceus and G. lucidum demonstrate beneficial protective potential for HT-22 cells without cytotoxicity. Both extracts show antioxidant, proliferative, and survival properties mediated through AhR-related pathways, suggesting positive impact on cognitive functions in the central nervous system.
  • Published in:Pharmacological Reports,
  • Study Type:In vitro Experimental Study,
  • Source: PMID: 40810764, DOI: 10.1007/s43440-025-00767-w
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