In a recent study published in The Journal of Neurochemistry, scientists from The University of Queensland report that the active compound from an edible mushroom, Hericium erinaceus, can enhance nerve growth and boost memory.
Study: Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory. Image Credit: Lubomir Dajc / Shutterstock.com
What are neurotrophins?
Neurotrophins are a family of proteins associated with the survival, development, functioning, and maintenance of neurons. These proteins aid dendritic branching by regulating binding specificity for tropomyosin receptor kinase (Trk) and p75 neurotrophin receptors.
The mammalian neurotrophin family consists of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 4/5 (NT4/5), and neurotrophin 3 (NT3). BDNF is highly expressed in the adult central nervous system (CNS) among the different neurotrophins. Moreover, BDNF plays a vital role in the proper functioning of neurons in the hippocampus and cortex region of the brain, both of which are associated with memory acquisition and learning.
An impairment in the BDNF pathway is associated with several diseases, including schizophrenia, Alzheimer's disease, Rett syndrome, and Huntington's disease. As a result, neurotrophins are often targeted for treating neurological and neurodegenerative disorders.
Nevertheless, exogenous neurotrophin-based treatments have failed in clinical trials due to poor blood-brain barrier (BBB) permeability and off-target effects. As a result, scientists explored alternative plant-based interventions that can boost endogenous BDNF levels and elevate TrkB activity.
Mushrooms for neurological treatments
Traditionally, H. erinaceus, also known as Lion's Mane mushroom, has been used for the prophylactic treatment of cancers and stomach aches. However, H. erinaceus is a nootropic fungus with a prominent neurotrophic profile due to bioactive compounds, such as hericerins, erinacines, alkaloids, steroids, and polysaccharides.
Both in vitro and in vivo studies related to nerve injury have revealed that hericenones and erinacines can successfully cross the BBB to elicit neuroprotective effects.
Extracts from these so-called ‘lion’s mane’ mushrooms have been used in traditional medicine in Asian countries for centuries, but we wanted to scientifically determine their potential effect on brain cells.”
In the current study, researchers from The University of Queensland investigate whether H. erinaceus extract could affect TrkB-dependent central neuronal function.
The neurotrophic effect of H. erinaceus extracts
The major compounds of H. erinaceus were extracted, purified, and identified. Later, their function in neuronal morphology and TrkB signaling in hippocampal neurons was assessed.
Although H. erinaceus contains 20 out of 24 known diterpenoids, four aromatic compounds were purified in the current study. These included N-de phenylethyl isohericerin (NDPIH), hericene A, corallocin A, and 4-[3′,7′- dimethyl-2′,6′-octadienyl]-2-formyl-3-hydroxy-5- methyoxybenzyl alcohol.
Crude and purified H. erinaceus extracts exhibited BDNF-like neurotrophic activity in both in vitro cultured hippocampal neurons and in vivo paradigm models of learning. In addition, these extracts promoted neurite outgrowth and improved memory.
Previous studies have shown that corallocin A induces NGF and BDNF expression in astrocytes, whereas hericenones induce NGF secretion from PC12 cells. NGF and BDNF supplements have also been used to enhance neural survival and axonal regrowth after spinal cord injury.
Based on their in vitro and in vivo experiments, the authors claimed their study to be the first to report a pro-BDNF signal-enhancing activity for H. erinaceus and hericene A to be the active component responsible for its neurotrophic function. More specifically, hericene A promoted neuritogenesis and boosted memory at a low concentration of 5 mg/kg/day. Furthermore, consistent with previous studies, the current study revealed the presence of polysaccharides in H. erinaceus extracts that exhibited neurotrophic activity.
The super-resolution structured illumination microscopic analysis of cells treated with H. erinaceus extracts exhibited enlarged growth cone morphology. This growth is essential for brain cells to sense their environment and develop new connections with other neurons in the brain.
Notably, dietary supplementation with H. erinaceus crude extract significantly increased recognition memory. Furthermore, supplementation with 20 to 50 times lower concentration of purified hericene A equally enhanced recognition memory.
In vivo experiments with rodents treated with H. erinaceus crude extracts revealed increased BDNF and TrkB downstream activation effectors levels. Mechanistically, hericene A acted through an unknown complementary pathway to elevate ERK1/2 signaling.
Hericene A from H. erinaceus was found to be a potent bioactive compound that enhanced memory through a novel signaling pathway associated with the ERK1/2 signaling pathway. In the future, more research is needed to validate the findings reported in this study.
- Martínez- Mármol, R., Chai, Y., Conroy, J. N., et al. (2023) Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory. Journal of Neurochemistry. doi:10.1111/jnc.15767