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

Pharmacol Rep. 2025 Dec;77(6):1557-1572. doi: 10.1007/s43440-025-00767-w. Epub 2025 Aug 14.

Abstract

Background: The proper functioning of the nervous system determines the homeostasis of the entire body. There are many known approaches designed to positively stimulate the functions of the central nervous system by applying various plants and fungal extracts, but their course of action is poorly understood. Hericium erinaceus and Ganoderma lucidum are examples of fungi with medicinal properties and with a positive health-promoting effect. Therefore, the aim of our study was to evaluate the effect of H. erinaceus or G. lucidum M-CFS with their active metabolites alone and/or in co-treatment with CAY10464 [antagonist of aryl hydrocarbon receptor (AhR)] on the metabolic parameters, cell cycle, and selected protein expression.

Methods: The study was based on the use of the resazurin reduction assay, flow cytometry analyses, and Western blotting in the mouse hippocampal neuronal cell line (HT-22) in vitro.

Results: The obtained results proved no cytotoxicity of the tested metabolites towards the HT-22 cells in the concentration range of 2.5% - 10% of culture medium. The cells treated with the tested compounds were characterized by an increase in the protein expression of SQSTM/p62, PCNA, c-SRC, SOD1, AhR, Beclin 1, and ERK1/2. Moreover, a significant role of AhR in the mechanism of action of the tested metabolites was observed at the protein expression level.

Conclusion: The observed increase in the proliferation-related markers in the HT-22 cells proves the beneficial protective potential of these M-CFSs. Given the findings, we speculate their positive impact on the cognitive functions in the central nervous system.

Clinical trial registration date: Not applicable.

Clinical trial number: Not applicable.

Keywords: Ganoderma lucidum; Hericium erinaceus; Cognitive functions; HT-22 cell line; M-CFS extract.

MeSH terms

  • Animals
  • Biological Products / pharmacology
  • Biological Products / therapeutic use
  • Brain-Gut Axis / drug effects
  • Cell Cycle / drug effects
  • Cell Line
  • Central Nervous System Agents* / analysis
  • Central Nervous System Agents* / pharmacology
  • Drug Evaluation, Preclinical
  • Hericium* / chemistry
  • Hericium* / metabolism
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Humans
  • Mice
  • Neurons* / drug effects
  • Neurons* / metabolism
  • Receptors, Aryl Hydrocarbon* / antagonists & inhibitors
  • Receptors, Aryl Hydrocarbon* / metabolism
  • Reishi* / chemistry
  • Reishi* / metabolism

Substances

  • Receptors, Aryl Hydrocarbon
  • Biological Products
  • Central Nervous System Agents