“The traditional medicinal mushroom Hericium erinaceus is known for enhancing peripheral nerve regeneration through targeting nerve growth factor (NGF) neurotrophic activity,” the researchers wrote in the Journal of Neurochemistry. “Here, we purified and identified biologically new active compounds from H. erinaceus based on their ability to promote neurite outgrowth in hippocampal neurons.”
According to the pre-clinical mouse study, the compounds isolated from the mushroom—N-de phenylethyl isohericerin (NDPIH) and its derivative hericene A—stimulate neuron projections, extending and connecting to other neurons.
The research was conducted at the University of Queensland in collaboration with researchers from Korea’s Gachon University and Chungbuk National University.
Supplementing the neurotrophins
A growing body of research supports the neuroprotective effects of lion’s mane (Hericium erinaceus) mushroom, so much so that it has earned itself the moniker “the smart mushroom” due to its ability to improve cognitive performance and reduce brain fog.
Previous studies attribute this activity to bioactive compounds in the mushroom that boost the neurotrophins, which promote neuronal survival, neurite outgrowth and dendritic branching. These include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and neurotrophin 4/5 (NT4/5).
“BDNF in particular, is highly expressed in the adult central nervous (CNS) and is critically important for the function of neurons located in areas of the brain involved in memory acquisition such as the hippocampus and the cortex,” the researchers noted.
They also point to research linking dysfunction of the BDNF pathway with several neurodegenerative and neurological disorders, including Alzheimer's disease, schizophrenia, Huntington's disease and Rett syndrome.
Citing previous studies that suggest that H. erinaceus extract promotes nerve growth factor (NGF) synthesis and secretion and affects the BDNF pathway, the researchers set out to determine whether their compounds might also affect central neuronal function.
Study details
The study evaluated the effects of a H. erinaceus ethanol extract and hericene A in six-week-old ICR male mice. On days 28 to 30 of the study period, the mice performed a Y-maze test and novel object test before they were sacrificed and their brains preserved for biochemical and immunohistochemistry analysis.
“Using super-resolution microscopy, we found the mushroom extract and its active components largely increase the size of growth cones, which are particularly important for brain cells to sense their environment and establish new connections with other neurons in the brain,” said Professor Frederic Meunier of the Queensland Brain Institute.
In addition, the researchers found that the NDPIH compound acted along a complementary neurotrophic pathway independent of TrkB (a receptor for brain-derived neurotrophic factor) to support downstream signaling in the brain.
“Mice fed with H. erinaceus crude extract and hericene A also exhibited increased neurotrophin expression and downstream signaling, resulting in significantly enhanced hippocampal memory,” they wrote. “Hericene A therefore acts through a novel pan-neurotrophic signaling pathway, leading to improved cognitive performance.”
Commenting independently on the study, Dennis E. Desjardin, PhD, professor emeritus at San Francisco State University and chief mycologist at Sempera Organics, called the in vitro and in vivo preclinical research promising with the data suggesting that the identified compounds may improve cognitive performance.
“The discovery of new bioactive compounds in extracts of the nootropic mushroom Hericium erinaceus supports previous research documenting a suite of cyathane diterpenoids that promote BDNF-like neurotrophic activity and nerve growth factor (NGF) synthesis and secretion,” he said.
Further study
Based on these study findings, Canada-based Arev Life Sciences Global Corporation just announced that it would launch its own research to identify advanced isolation technology for its proprietary extract.
“This is a very exciting finding,” Dr. Sateesh Apte, scientific advisory board member at Arev, said in a statement. “The neuroscience community is always trying to find pharmacologically active ingredients that would increase neuroplasticity in aging and degenerative conditions.”
Dr. Meunier told NutraIngredients-USA that the team will continue its investigation to decipher this new pathway and plans to initiate clinical trials to evaluate the effect in humans.
“Human clinical trials are the next necessary step to assure that the reported bioactive compounds can withstand challenges of the human gastrointestinal tract and are capable of crossing the blood-brain barrier and promote NGF- and BDNF-associated gene expression,” Dr. Desjardins said.
Source: Journal of Neurochemistry
“Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory”
doi: doi.org/10.1111/jnc.15767
Authors: Ramón Martínez-Mármol