Table 3.

Summary of the main in vitro and preclinical studies on H. erinaceus in the CNS. In the table the up arrows indicate an increase, and the down arrows indicate a decrease.

H. erinaceus Bioactive Compound	Target	Pathway/Intracellular Mechanism	Effect	Reference
Erinacine A/ erinacine A-enriched H. erinaceus mycelium (EAHEM)	NGF 1, ↑ NGF/proNGF ratio ↓ iNOS 2 ↑ IDE 5 ↓ 8-OHdG 7, iNOS, and TBARS 8 levels in mice brain	TrkA/Erk1/2 pathway Others? Phosphorylation of p38 MAPK 3 and CHOP 4. ? ?	Neuroprotection and nootropic in vitro. ↑ Neurite outgrowth. ↑ Neuronal proliferation. ↓ Cognitive decline during aging in a SAMP8 mouse model. Protection against stroke in rats. ↓ Inflammation. ↓ Cerebral β-amyloid plaque loading in AD 6 APPswe/PS1dE9 transgenic mice. ↑ Cognitive performances in AD APP/PS1 mice. ↓ Oxidative stress, inflammation, brain Aβ plaque number.	[46,77,78,79,84] [46] [69] [36]
Erinacine S	↑ IDE	?	↓ Cerebral β-amyloid plaque loading in AD APPswe/PS1dE9 transgenic mice.	[69]
Hericenone E	↑ NGF	MEK/ERK and PI3K-Akt pathways	↑ Neurite outgrowth in vitro.	[83]
Mix of Erinacine A and Hericenone C and D (sporophore and mycelium H. erinaceus extract)	↑ Hippocampal and cerebellar PCNA 9 and DCX 10 expression ↓ Cerebellar expression of IL-6 11, iNOS, COX-2 12, and SOD-1 13	? ?	↑ Neurogenesis and cognitive performances in aged frail mice. Inflammation and ↓ Oxidative stress in the cerebellum. ↑ Locomotor functions in aged frail mice.	[47] [39]
Ergothioneine-enriched primordium	↓ Cerebellar expression of iNOS and COX-2 ↓ Hippocampal expression of IL-6, Nrf2 14, SOD-1, COX-2, and iNOS. ↓ Hippocampal NMDAR1 15 and mGlutR2 16 receptors expression	? TGF-beta1 17	↓ Oxidative stress in the cerebellum and hippocampus, and of locomotor aging-related decline in frail mice. ↓ Hippocampal inflammation and oxidative stress. ↑ Glutamatergic neurotransmission. ↓ Cognitive aging-related decline in frail mice.	[41] [40]

Abbreviations: ¹ nerve growth factor (NGF), ² inducible nitric oxide synthase (iNOS), ³ mitogen-activated protein kinase (MAPK), ⁴ homologous protein (CHOP), ⁵ insulin-degrading enzyme (IDE), ⁶ Alzheimer’s disease (AD), ⁷ 8-hydroxy-2’-deoxyguanosine (8-OHdG), ⁸ thiobarbituric acid reactive (TBARS), ⁹ proliferating cell nuclear antigen (PCNA), ¹⁰ doublecortin (DCX), ¹¹ interleukin 6 (IL-6), ¹² cyclooxygenase-2 (COX-2), ¹³ superoxide dismutase 1 (SOD-1), ¹⁴ nuclear factor erythroid 2–related factor 2 (Nrf2), ¹⁵ N-methyl-D-aspartate receptor 1 (NMDAR1), ¹⁶ metabotropic glutamate receptor 2 (mGlutR2), ¹⁷ transforming growth factor beta 1 (TGF-beta1).