Tuesday, March 12, 2024

MYCOPHILIA

Exploring the therapeutic potential of natural mushroom compounds to address psychiatric disorders

Peer-Reviewed Publication

THE HEBREW UNIVERSITY OF JERUSALEM





New study indicates that mushroom extract might demonstrate superior efficacy compared to chemically synthesized psilocybin, especially in stimulating neuroplasticity and promoting the development of new connections between nerve cells—an essential attribute. This discovery unveils potential applications for addressing conditions such as depression, PTSD, and schizophrenia.

A new study led by Orr Shahar, a PhD student, and Dr. Alexander Botvinnik, under the guidance of researchers Dr. Tzuri Lifschytz and psychiatrist Prof. Bernard Lerer from the Hebrew University-Hadassah Medical Center, suggests that mushroom extract containing psilocybin may exhibit superior efficacy when compared to chemically synthesized psilocybin.

The research, focusing on synaptic plasticity in mice, unveils promising insights into the potential therapeutic benefits of natural psychedelic compounds in addressing psychiatric disorders. The study indicates that psilocybin-containing mushroom extract could have a more potent and prolonged impact on synaptic plasticity in comparison to chemically synthesized psilocybin.

Millions of individuals globally, constituting a significant portion of the population, grapple with psychiatric conditions that remain unresponsive to existing pharmaceutical interventions. Alarming statistics reveal that 40% of individuals experiencing depression find no relief from currently available drugs, a trend similarly observed among those with OCD. Moreover, with approximately 0.5% of the population contending with schizophrenia at any given time, there exists a pressing demand for innovative solutions tailored to those who derive no benefit from current medications. In response to this urgent need, psychedelic drugs are emerging as promising candidates capable of offering transformative solutions.

The study's preliminary findings shed light on the potential divergence in effects between psilocybin-containing mushroom extract and chemically synthesized psilocybin. Specifically, the research focused on the head twitch response, synaptic proteins related to neuroplasticity, and metabolomic profiles in the frontal cortex of mice.

The results indicate that psilocybin-containing mushroom extract may exert a more potent and prolonged effect on synaptic plasticity when compared to chemically synthesized psilocybin. Significantly, the extract increased the levels of synaptic proteins associated with neuroplasticity in key brain regions, including the frontal cortex, hippocampus, amygdala, and striatum. This suggests that psilocybin-containing mushroom extract may offer unique therapeutic effects not achievable with psilocybin alone.

 

Metabolomic analyses also revealed noteworthy differences between psilocybin-containing mushroom extract and chemically synthesized psilocybin. The extract exhibited a distinct metabolic profile associated with oxidative stress and energy production pathways.

These findings open up new possibilities for the therapeutic use of natural psychedelic compounds, providing hope for those who have found little relief in conventional psychiatric treatments. As the demand for innovative solutions continues to grow, the exploration of psychedelic drugs represents a crucial avenue for the development of transformative and personalized medicines.

Additionally - in Western medicine, there has historically been a preference for isolating active compounds rather than utilizing extracts, primarily for the sake of gaining better control over dosages and anticipating known effects during treatment. The challenge with working with extracts lay in the inability, in the past, to consistently produce the exact product with a consistent compound profile. Contrastingly, ancient medicinal practices, particularly those attributing therapeutic benefits to psychedelic medicine, embraced the use of extracts or entire products, such as consuming the entire mushroom. Although Western medicine has long recognized the "entourage" effect associated with whole extracts, the significance of this approach gained recent prominence.

A major challenge with natural extracts lies in achieving a consistently stable compound profile, especially with plants; however, mushrooms present a unique case. Mushroom compounds are highly influenced by their growing environment, encompassing factors such as substrate composition, CO2/O2 ratio, light exposure, temperature, and microbial surroundings. Despite these influences, controlled cultivation allows for the taming of mushrooms, enabling the production of a replicable extract.

This research not only underscores the superiority of extracts with diverse compounds but also highlights the feasibility of incorporating them into Western medicine due to the controlled nature of mushroom cultivation.

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Unveiling Inaoside A: An antioxidant derived from mushrooms


Researchers in Japan discover a new antioxidant compound Inaoside A in the edible mushroom, Laetiporus cremeiporus


SHINSHU UNIVERSITY

Discovering a new antioxidant compound, Inaoside A from Laetiporus cremeiporus 

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RESEARCHERS FROM JAPAN DISCOVERED A NEW ANTIOXIDANT, INAOSIDE A, ALONG WITH THREE OTHER KNOWN BIOACTIVE COMPOUNDS, FROM LAETIPORUS CREMEIPORUS, AN EDIBLE MUSHROOM VARIETY.

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CREDIT: ATSUSHI KAWAMURA FROM SHINSHU UNIVERSITY, JAPAN




Natural products have unique chemical structures and biological activities and can play a pivotal role in advancing pharmaceutical science. In a pioneering study, researchers from Shinshu University discovered Inaoside A, an antioxidant derived from Laetiporus cremeiporus mushrooms. This breakthrough sheds light on the potential of mushrooms as a source of therapeutic bioactive compounds.

The search for novel bioactive compounds from natural sources has gained considerable momentum in recent years due to the need for new therapeutic agents to combat various health challenges. Among a diverse array of natural products, mushrooms have emerged as a rich reservoir of bioactive molecules with potential pharmaceutical and nutraceutical applications. The genus Laetiporus has attracted attention for its extracts exhibiting antimicrobial, antioxidant, and antithrombin bioactivities. The species Laetiporus cremeiporus, spread across East Asia, has also been reported to show antioxidant properties. However, the identification and characterization of specific antioxidant compounds from this species have not been conducted.

In a groundbreakng study, researchers led by Assistant Professor Atsushi Kawamura from the Department of Biomolecular Innovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, along with Hidefumi Makabe from the Department of Agriculture, Graduate School of Science and Technology, Shinshu University, and Akiyoshi Yamada from the Department of Mountain Ecosystem, Institute for Mountain Science, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, recently discovered the antioxidant compound derived from L. cremeiporus.

The researchers collected fresh fruiting bodies of L. cremeiporus from the Ina campus of Shinshu University. The obtained extracts were concentrated and partitioned between water and ethyl acetate. After this, the extracts were subjected to advanced chromatographic techniques, which led to the successful isolation of Inaoside A, a new antioxidant phenolic compound, along with three other well-characterized bioactive compounds, i.e., 5'-S-methyl-5'-thioadenosine (MTA), nicotinamide, and adenosine. They reported their findings in an article that was made available online on 20 January 2024 and subsequently published in the journal Heliyon.

Our study marks the pioneering discovery of Inaoside A from an extract of the edible mushroom Laetiporus cremeiporus. To date, there has been only one prior report on the biological function of an extract of L. cremeiporus. We are the first to uncover the isolation of an antioxidant compound from L. cremeiporus,” states Professor Kawamura, highlighting the breakthrough research.

Next, the researchers wanted to determine the structure of the newly found antioxidant compound. For this, they utilized one and two- dimensional NMR and other spectroscopic analyses. The structure of Inaoside A revealed a planar configuration. With a molecular formula of C17H24O7, the compound was found to feature a distinctive ribose moiety, identified as α-ribofuranoside through stereochemical analysis. Subsequent investigation into the absolute stereochemistry confirmed the D-ribose configuration, thereby reinforcing the planar structure of this compound.

The mushroom extracts were then isolated into fractions to determine the antioxidant activities of the four isolated bioactive compounds. These fractions were then examined by DPPH radical scavenging and superoxide dismutase assays. The findings were noteworthy as the DPPH radical scavenging activity exhibited by Inaoside A was significant, showing 80% inhibition at 100 μg/mL, indicative of its significant antioxidant properties. The IC50 value of Inaoside A was determined to be 79.9 μM, further highlighting its efficacy as an antioxidant agent.

What are the objectives of the researchers following the discovery of Inaoside? Professor Kawamura reveals, “We are now focusing on investigating the chemical compositions and biological properties of natural compounds obtained from mushrooms. Our goal is to uncover the potential of edible mushrooms as functional foods through this discovery.”

The identification of Inaoside A as an antioxidant from Laetiporus cremeiporus marks a significant breakthrough in natural product research, highlighting the potential of mushrooms as a source of therapeutic bioactive compounds. These findings may lead to the development of novel antioxidant-based therapies for various health conditions. Further studies should focus on synthetic research and detailed investigations into the biological activity of Inaoside A, aiming to harness its potential as a pharmaceutical lead compound.

 

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About Shinshu University

Shinshu University is a national university founded in 1949 and located nestling under the Japanese Alps in Nagano known for its stunning natural landscapes. Our motto, "Powered by Nature - strengthening our network with society and applying nature to create innovative solutions for a better tomorrow" reflects the mission of fostering promising creative professionals and deepening the collaborative relationship with local communities, which leads to our contribution to regional development by innovation in various fields. We’re working on providing solutions for building a sustainable society through interdisciplinary research fields: material science (carbon, fiber, and composites), biomedical science (for intractable diseases and preventive medicine) and mountain science and aiming to boost research and innovation capability through collaborative projects with distinguished researchers from the world. For more information visit https://www.shinshu-u.ac.jp/english/ or follow us on X (Twitter) @ShinshuUni for our latest news.

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