Newly Discovered Compounds in Lion's Mane Boosts Nerve Growth and Improves Memory

Lately, lion’s mane (Hericium erinaceus) has been gaining much attention in both the medical and mushroom worlds due to its potential as a powerful brain booster. It is believed that lion’s mane can act as a nootropic, a stress reliever, and even help improve gut health. A new study from the University of Queensland in Australia has identified new active compounds in the mushroom that can encourage neurite outgrowth, which connects developing neurons to other neurons throughout the brain, leading to better communication between brain cells. This finding may be a valuable tool in understanding exactly why a lion’s mane works the way it does.

What we already knew about lion’s mane

Lion’s mane mushrooms have been used in Traditional Chinese Medicine (TCM) for hundreds of years to support mental function, promote digestion, and replenish the spleen. The mushroom contains two well-known active compounds, hericenones, and erinacines (1). The compounds are known to improve nerve growth factor (NGF) biosynthesis, an important neurotrophin protein that helps grow, adapt, and support sympathetic and embryonic sensory neurons in the brain while helping prevent cell death (2). Hericenones are found in the fruiting bodies of lion’s mane, while erinacines are located in the mycelium. The mushroom contains eight different types of hericenone compounds (A through H) and fifteen kinds of erinacines (A through K), many of which have neuroprotective properties. The compounds cannot act alone, however. Hericenone does not initiate NGF on its own, but when combined with erinacines, it stimulates neurite outgrowth and NGF secretion (3). Erinacines can easily cross the blood-brain barrier, allowing hericenones to cross along with it when taken together.

Past human studies

Several studies have been done on humans to demonstrate the positive impact of lion’s mane compounds on the brain. In one double-blind, placebo-controlled study, researchers orally administered 250mg tablets of lion’s mane to a group of individuals aged 50 to 80 with mild cognitive impairments (4).

 Participants took the supplement three times a day for sixteen weeks and were examined through tests every four weeks. Researchers found that the individuals who took the lion’s mane supplements had significant increases in their cognitive function scores before treatment. The study also concluded that the scores decreased four weeks after terminating the daily supplementation routine. Ultimately, the study concluded that lion’s mane could effectively improve mild cases of cognitive impairment.

Another small-scale human study found that lion’s mane could have an effect on reducing anxiety and depression (5). The study tested thirty menopausal women and fed them cookies on a daily basis infused with two grams of powdered lion’s mane fruiting bodies. Meanwhile, the control group was fed regular cookies. After four weeks, the group that was fed the cookies containing lion’s mane had a decreased depression scale and indefinite complaints score that was significantly lower than the placebo group. Those who took lions mane also reported better concentration and less irritability and anxiety than those in the control. The study concluded that daily consumption of lion’s mane has the potential to reduce depression and anxiety levels.

Past animal studies

Many more studies that have been done on mice have also concluded positive findings of lion’s mane and its impact on the brain. In one study, originally posed in the International Journal of Molecular Science, a group of mice received an injection of a peptide called D-galactose and AlCl3 for the span of ten weeks. The injections induced symptoms of Alzheimer’s Disorder (AD) in the mice to compare their brains to human Alzheimer cases.

After developing AD, the mice were tested with a timed maze to establish a baseline score. Researchers tracked their movement and how long it took for the mice to complete the maze. Then, the mice were given daily dosages of lion’s mane extract for four weeks. Afterward, the mice completed the same maze test with significantly faster times compared to their baseline testing and control group. The test results found that daily use of lion’s mane could notably improve memory abilities and learning performance in mice (6).

Another study found that mice with learning and memory deficits could benefit from lion’s mane supplementation. In the study, mice were given amyloid peptide, which induces mental deficits. These mice were given lion’s mane for 23 days. Then they were tested with mazes and object recognition tests, which found that the treated mice had higher cognition and test scores than the baseline testing and the controlled group (7).

Currently, there is more testing on mice than there is on humans for the studies of many compounds, including those found in lion’s mane. This is because mice are mammals and genetically similar to humans, so they have similar anatomical and physiological processes. While testing to see the efficiency of substances, mice are more accessible and cost-effective than human studies, as it is difficult for researchers to get a substantial amount of human participants for their trials. Though these tests are not done on humans, their promising results are likely applicable to the human brain. These studies will serve as essential background knowledge in the future when more human clinical studies are conducted.

What the new study has concluded

The new study, published in the Journal of Neurochemistry, has found further evidence of exactly how and why lion’s mane works as such a potent brain supplement. Scientists from the University of Queensland worked in collaboration with researchers from Gachon University and Chunbuk  National University in Korea, using their prior knowledge of hericenones and erinacines to isolate and test new compounds found in the mushroom. Through super-resolution structured illumination microscopy, researchers discovered that the active compounds enhanced the size of growth cones, therefore facilitating the production of axons, which promote neuron connectivity (8). The new compound N-de phenylethyl isohericerin (NDPIH) works in combination with hericenone A, which is a derivative of NDPIH. In the study, mice were given the combination of the two compounds and tested to see how their brains were altered. Researchers conducted maze and behavioral tests, along with in vitro experiments on the cultured brain cells of mice. They found that the combination of the new compound and hericenone A amplified neurotrophin production, which is important for healthy brain function. The laboratory tests concluded that the compounds had neurotrophic effects and promoted neuron connections which can, in turn, improve memory and cognitive performance.

This study is just one of the many more to come as scientists grow to understand just exactly why lion’s mane mushrooms have shown promising results in improving the brain’s abilities and functions. Before, scientists were only aware of hericenones and erinacines as the bioactive compounds that caused the effects of lion’s mane. However, this recent study proves that there are still more molecular mechanisms that make up the mushroom. By recognizing the compounds that make lion’s mane such a potent brain medicine, researchers can fully isolate them and determine the science behind the mushroom as a neurological medicine. While the testing of this compound has not yet been done on humans, these findings are essential to our understanding of lion’s mane and its potential to alter the brain and improve memory formation.

References

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2. “Nerve Growth Factor - an Overview | ScienceDirect Topics.” n.d. Science Direct. https://www.sciencedirect.com/topics/neuroscience/nerve-growth-factor.
3. Phan, Chia-Wei, Guan-Serm Lee, Sok-Lai Hong, Yuin-Teng Wong, Robert Brkljača, Sylvia Urban, Sri Nurestri Abd Malek, and Vikineswary Sabaratnam. 2014. “Hericium Erinaceus (Bull.: Fr) Pers. Cultivated under Tropical Conditions: Isolation of Hericenones and Demonstration of NGF-Mediated Neurite Outgrowth in PC12 Cells via MEK/ERK and PI3K-Akt Signaling Pathways.” Food Funct. 5 (12): 3160–69. https://doi.org/10.1039/c4fo00452c.
4. Mori, Koichiro, Satoshi Inatomi, Kenzi Ouchi, Yoshihito Azumi, and Takashi Tuchida. 2009. “Improving Effects of the Mushroom Yamabushitake (Hericium Erinaceus) on Mild Cognitive Impairment: A Double-Blind Placebo-Controlled Clinical Trial.” Phytotherapy Research 23 (3): 367–72. https://doi.org/10.1002/ptr.2634.
5. Nagano, Mayumi, Kuniyoshi Shimizu, Ryuichiro Kondo, Chickako Hayashi, Daigo Sato, Katsuyuki Kitagawa, and Koichiro Ohnuki. 2010. “Reduction of Depression and Anxiety by 4 Weeks Hericium Erinaceus Intake.” Biomedical Research (Tokyo, Japan) 31 (4): 231–37. https://doi.org/10.2220/biomedres.31.231.
6. Zhang, Junrong, Shengshu An, Wenji Hu, Meiyu Teng, Xue Wang, Yidi Qu, Yang Liu, Ye Yuan, and Di Wang. 2016. “The Neuroprotective Properties of Hericium Erinaceus in Glutamate-Damaged Differentiated PC12 Cells and an Alzheimer’s Disease Mouse Model.” International Journal of Molecular Sciences 17 (11): 1810. https://doi.org/10.3390/ijms17111810.
7. Mori, Koichiro, Yutaro Obara, Takahiro Moriya, Satoshi Inatomi, and Norimichi Nakahata. 2011. “Effects of Hericium Erinaceus on Amyloid β(25-35) Peptide-Induced Learning and Memory Deficits in Mice.” Biomedical Research 32 (1): 67–72. https://doi.org/10.2220/biomedres.32.67.
8. Martínez‐Mármol, Ramón, YeJin Chai, Jacinta N. Conroy, Zahra Khan, Seong‐Min Hong, Seon Beom Kim, Rachel S. Gormal, 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, January. https://doi.org/10.1111/jnc.15767.