Neuroprotective Metabolites of Hericium erinaceus Promote Neuro-Healthy Aging

Int J Mol Sci. 2021 Jun 15;22(12):6379. doi: 10.3390/ijms22126379.


Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, typically linked to chronic systemic inflammation, i.e., inflammaging. In the current study, we investigated the effect of a two-month oral supplementation with standardized extracts of H. erinaceus, containing a known amount of Erinacine A, Hericenone C, Hericenone D, and L-ergothioneine, on locomotor frailty and cerebellum of aged mice. Locomotor performances were monitored comparing healthy aging and frail mice. Cerebellar volume and cytoarchitecture, together with inflammatory and oxidative stress pathways, were assessed focusing on senescent frail animals. H. erinaceus partially recovered the aged-related decline of locomotor performances. Histopathological analyses paralleled by immunocytochemical evaluation of specific molecules strengthened the neuroprotective role of H. erinaceus able to ameliorate cerebellar alterations, i.e., milder volume reduction, slighter molecular layer thickness decrease and minor percentage of shrunken Purkinje neurons, also diminishing inflammation and oxidative stress in frail mice while increasing a key longevity regulator and a neuroprotective molecule. Thus, our present findings demonstrated the efficacy of a non-pharmacological approach, based on the dietary supplementation using H. erinaceus extract, which represent a promising adjuvant therapy to be associated with conventional geriatric treatments.

Keywords: Hericium erinaceus; cerebellum; ergothioneine; frailty; healthy aging; inflammaging; neuroprotection; oxidative stress.

MeSH terms

  • Animals
  • Cyclooxygenase 2 / metabolism
  • Frailty / metabolism
  • Frailty / physiopathology
  • Glial Fibrillary Acidic Protein / metabolism
  • Healthy Aging / drug effects
  • Healthy Aging / physiology*
  • Hericium / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Inflammation / pathology
  • Interleukin-6 / metabolism
  • Male
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Neuroprotection* / drug effects
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress / drug effects
  • Plant Extracts / pharmacology
  • Sirtuin 1 / metabolism
  • Superoxide Dismutase / metabolism


  • Glial Fibrillary Acidic Protein
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Interleukin-6
  • Plant Extracts
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Superoxide Dismutase
  • Sirtuin 1