Researchers have found that compounds from the lion’s mane mushroom, particularly hericene A, promote nerve cell growth, increase the production of brain-boosting molecules called neurotrophins, and improve memory performance in mice, suggesting their potential as cognitive enhancers. Their findings have been published in the Journal of Neurochemistry.
The study was motivated by the desire to explore the potential cognitive-enhancing effects of compounds found in the edible mushroom Hericium erinaceus, commonly known as lion’s mane mushroom. This mushroom has been traditionally used in Asian countries for various health benefits, including its potential effects on brain health and memory. The researchers aimed to scientifically determine the effects of these compounds, with a specific focus on nerve growth and memory-related processes.
“Natural products have been fashioned by millions of years of evolution, which have left us with a humongous multilayered puzzle to try to figure out: which molecule for which application?” explained study author Frédéric A. Meunier, a professor at The University of Queensland and leader of the Single Molecule Neuroscience Laboratory.
“I have previously worked on natural products called neurotoxins from either bacteria (botulinum toxin AKA Botox), algae (dinoflagellate), worms or (cone shell). Some of the molecules contained in these species have exquisite activities. So much so that some of them are now used as therapeutics or for cosmetic purposes.”
“Similarly, molecules from various mushrooms have been in used in biomedical research for years. Therefore, when given the opportunity, I offered to test extracts from the lion’s mane mushroom in my laboratory to try to identify active compounds and work out their modes of action.”
The researchers employed a combination of cell culture experiments, molecular analyses, and animal studies to investigate the effects of the lion’s mane mushroom compounds on nerve growth and memory enhancement.
The researchers purified specific compounds from the mushroom extracts. Specifically, they isolated a compound called N-de phenylethyl isohericerin (NDPIH) and its hydrophobic derivative, known as hericene A. These compounds were found to be highly effective in stimulating the extensive growth of axons and branching of neurites in hippocampal neuron cultures, even in the absence of serum in the growth medium.
Extracts of the lion’s mane mushroom had neurotrophic activity similar to brain-derived neurotrophic factor (BDNF), a protein that supports the growth and survival of nerve cells. This activity was observed both in cultured hippocampal neurons (nerve cells in the brain’s memory center) and in paradigm models of learning in vivo (live animals).
“I was very surprised by how much neurons in culture loved these extracts,” Meunier told PsyPost. “Neurons are very tricky to culture and more often than not decide to die unless given copious amount of serum and neurotrophins such as BDNF. The lion’s mane mushroom extracts promote the generation of very long neurites and many branches even in the absence of serum and BDNF which was surprising in itself.”
“Further, at the tip of each of these branches, there is normally a tiny structure called a growth cone that is capable of sensing the environment and orientate the growth of its particular branch. In the presence of the lion’s mane mushroom compounds, the size of these growth cones was hugely increased with some being even larger than the cell body of the neuron. It would be like having a hand larger than your own body, so even more surprising!”
“These growth cones are search engines capable of finding target neurons and establishing connections between them,” Meunier explained. “This suggested that the compounds could promote the establishment of new connections between neurons in the brain, which is at the core of memory formation. This is why we tested various paradigms of memory to see if the compound had any effect which we found they had.”
To investigate the effects of lion’s mane mushroom compounds on memory enhancement, the researchers used male mice. These mice were divided into different groups: a control group, a positive control group (given piracetam, a known memory-enhancing drug), and groups given different doses of mushroom extracts. The mice were then subjected to behavioral tests to assess their cognitive abilities.
The Y-maze test was used to evaluate spontaneous alternation behavior, which reflects spatial working memory. In this test, the mice were placed in a Y-shaped maze and their movement patterns were observed. The novel object recognition task assessed recognition memory. Mice were exposed to familiar and novel objects, and the time spent exploring each object was measured.
The results of the animal studies indicated that both crude extracts from the lion’s mane mushroom and the compound hericene A have the potential to enhance short-term and spatial memory.
When the mice were administered the highest dose of the mushroom extract (250 mg/kg) or hericene A, they exhibited significantly increased interaction with the novel object compared to the control group. This enhanced interaction suggests improved short-term memory acquisition Similarly, both doses of the mushroom extract (100 mg/kg and 250 mg/kg) and hericene A displayed were associated with significant increments in spontaneous alternation behavior. This indicates that the mice treated with the extract and hericene A showed improved spatial memory.
“Our study identified highly active chemical compounds from the lion’s mane mushroom that have an effect on the growth of brain cells and enhanced memory in mice,” Meunier told PsyPost. “Lion’s mane mushroom based products are available as nootropics from many companies. Anyone can buy these, but it is unclear which products have the compounds we identified and at what concentration.
“We are currently developing tools (functional assay and mass spectrometry) to directly measure the activity of the Lion’s mane mushroom compounds. We are making these tools available to interested parties. Ultimately, our hope is that this will help determining what the best products are and allow interested companies to optimise their products for health benefits. The active molecules identified can be used as stepstone to help design a new generation of therapeutic molecules that will need to be tested and optimized for a range of brain diseases.”
While the study provides valuable insights into the potential memory-enhancing effects of compounds from the lion’s mane mushroom, there are some limitations that should be considered. The study primarily used mice as animal models to assess the effects of the lion’s mane mushroom extracts. Findings from animal studies may not directly translate to humans. the direct clinical relevance of these findings in treating cognitive disorders or improving memory in humans remains to be established.
“There is plenty of work to do at many different levels,” Meunier said. “First, we need to understand the molecular mechanism of action which has not been fully solved yet. Second, we need to understand how we can best use these molecules in health and various diseases. We are awaiting the results of new clinical trials mostly in Alzheimer’s disease, but these molecules could have plenty of novel applications. Finally, the chemistry of these compounds could serve as basis for new generation of new therapeutics for a range of brain disease to optimize their efficacies.”
“The field of mushrooms is full of incredibly knowledgeable and passionate people, and it is great to interact with them. We are hoping to put together a hub of scientists and companies to fasttrack the discovery and use of more mushroom compounds for medical and health applications,” he added.
The study, “Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory“, was authored by Ramón Martínez-Mármol, YeJin Chai, Jacinta N. Conroy, Zahra Khan, Seong-Min Hong, Seon Beom Kim, Rachel S. Gormal, Dae Hee Lee, Jae Kang Lee, Elizabeth J. Coulson, Mi Kyeong Lee, Sun Yeou Kim, and Frédéric A. Meunier.