Pharmaceutical Fungi: A Journey From Statins To Future Medical Breakthroughs
By Josh Shearer on 06/23/2023
In the dynamic world of medical science, fungi have emerged as the underappreciated heroes of significant breakthroughs. The diverse kingdom of fungi... To edit this post, navigate to the admin dashboard.
Statins: Fungi's Flagship Contribution to Pharmaceuticals
Statins, a class of drugs used to lower cholesterol levels, exemplify the groundbreaking impact of fungi on pharmaceuticals. They trace their origins to a humble fungus, Penicillium citrinum, from which the first statin, mevastatin, was extracted. In the late 1970s, Akira Endo's breakthrough discovery of statins revolutionized the management of cardiovascular diseases and highlighted the medicinal potential hidden within fungi. Statins operate by inhibiting an enzyme known as HMG-CoA reductase, thereby controlling the body's cholesterol production. This attribute has had enormous implications in combating cardiovascular diseases, one of the leading causes of death worldwide. With millions of prescriptions written annually, statins are a testament to how fungi-derived compounds can achieve mainstream acceptance and utilization in healthcare.Medicinal Mushrooms in Modern Medicine
But statins are just the tip of the iceberg. Beyond these lipid-lowering marvels, the kingdom of fungi has much more to offer. The use of medicinal mushrooms, for instance, dates back centuries, with early civilizations recognizing their potential in healing and cauterizing wounds. Today, we are rediscovering and validating these ancient wisdoms through modern scientific methods. Ganoderma lucidum (Reishi), known as the lingzhi mushroom, has more than 16,000 genes that code for over 200,000 compounds. Within this wealth of bioactive substances, 400 have been identified as "active constituents." This makes mushrooms potent miniature pharmaceutical factories, rich in novel constituents ready for medical investigation.With advancements in mycelium tissue culture and novel testing methods, it's possible to harness these active constituents and their synergies. However, the real potential lies not only in isolated compounds but also in their interplay. The combined effect of multiple compounds working in tandem could present a new frontier in medicine, enabling us to treat complex health conditions more effectively.Peering into the Future: Mushroom Medical Breakthroughs
As we delve deeper into the mushroom kingdom, we unveil an array of potential future medical breakthroughs. Fungi are, in essence, nature's miniature pharmaceutical factories, synthesizing a plethora of unique, biologically active compounds.Fungi and Antibiotic Resistance
Fungi and Antibiotic Resistance: With the looming threat of antibiotic resistance, fungi could hold the keys to new antibiotics. Already, we owe the discovery of the first antibiotic, Penicillin, to a fungus. New fungal species, with their untapped genomic potential, could usher in the next generation of antibiotics.Neurodegenerative Diseases and Fungi
Alzheimer's and Parkinson's diseases remain elusive in terms of their cure. However, certain fungi, like Lion's Mane (Hericium erinaceus), have shown promise in stimulating nerve growth factor synthesis, suggesting potential roles in managing neurodegenerative conditions. Erinacines and hericenones are two groups of bioactive compounds found in the Lion's Mane mushroom, scientifically known as Hericium erinaceus. Both these compounds have garnered significant interest due to their potential neuroprotective and neuroregenerative properties.Erinacines
Erinacines, specifically found in the mycelium of the Lion's Mane mushroom, are diterpenoid compounds. They have attracted considerable attention because of their ability to stimulate the production of nerve growth factor (NGF). NGF is a protein that plays a crucial role in the growth, maintenance, and survival of nerve cells, particularly neurons. It's essential for the proper functioning of the central and peripheral nervous system.Research has shown that erinacines can pass through the blood-brain barrier, a membrane that prevents potentially harmful substances in the blood from entering the brain. This ability is particularly important, as many drugs cannot cross this barrier, limiting their potential for treating brain-related conditions. Once in the brain, erinacines can stimulate the synthesis of NGF, which in turn may aid in the protection and repair of nerve cells, offering potential therapeutic benefits for neurodegenerative diseases like Alzheimer's and Parkinson's.Hericenones
Hericenones are aromatic compounds found in the fruiting body of the Lion's Mane mushroom. Similar to erinacines, hericenones can also stimulate the synthesis of NGF. However, they are believed to be less potent than erinacines in stimulating NGF.The potential ability of hericenones to induce NGF synthesis means they may also help protect and regenerate nerve cells. Thus, they may offer potential therapeutic benefits in managing neurodegenerative diseases and possibly improving cognitive function.It's important to note that while the initial research on erinacines and hericenones is promising, more comprehensive studies, particularly in humans, are needed to fully understand their potential therapeutic effects and safety profiles.Fungal Immunotherapy
The immune-modulating properties of various mushrooms point towards the possibility of fungal-based immunotherapy. Compounds like β-glucans, derived from fungal cell walls, have demonstrated potential in enhancing immune response, potentially assisting in combating a variety of diseases, from infections to cancer. Several mushroom species, such as lentinan, schizophyllan, and krestin, have shown potential as anticancer agents due to their immune-modulating effects. The high molecular weight of these compounds makes them effective at triggering necessary immune responses in the body, and ongoing research is investigating their effect on cell processes like apoptosis, angiogenesis, and metastasis. Mushroom Metabolites and Mental Health Psilocybin, a compound found in certain species of mushrooms, has sparked interest due to its potential role in treating various mental health disorders, including depression and post-traumatic stress disorder (PTSD). Some studies suggest that psilocybin-assisted therapy can catalyze profound experiences that lead to lasting improvements in mental health. By understanding and harnessing the therapeutic potential of fungi, we could trigger a paradigm shift in psychiatry and mental health treatment. However, while the early research is promising, much remains to be understood about how these compounds can be safely and effectively integrated into mental health care.The Collaborative Fungal Future
As we journey through the world of pharmaceutical fungi, it is essential to remember that true progress lies in the synergy between traditional knowledge and modern scientific methods. The union of ancient wisdom with contemporary science can fast-track our understanding of fungal metabolites and their medicinal worth.There is no doubt that fungi represent a frontier of untapped potential in pharmaceuticals, teeming with opportunities. From statins to potential cures for neurodegenerative diseases and mental health disorders, fungi have much to offer. As we continue to unlock the mysteries within this kingdom, we can look forward to a new era of pharmaceutical innovation, profoundly impacting global health.References
Medicinal Mushrooms as Multicomponent Mixtures—Demonstrated with the Example of Lentinula edodes
Effect of erinacine A-enriched Hericium erinaceus supplementation on cognition: A randomized, double-blind, placebo-controlled pilot study
Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins
Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory
Erinacine S from Hericium erinaceus mycelium promotes neuronal regeneration by inducing neurosteroids accumulation
The protective effects of a novel polysaccharide from Lentinus edodes mycelia on islet beta (INS-1) cells damaged by glucose and its transportation mechanism with human serum albumin
Neuroprotective effects of cordycepin inhibit Abeta-induced apoptosis in hippocampal neurons
Investigation of Lovastatin, the Anti-hypercholesterolemia Drug Molecule from Three Oyster Mushroom Species
Inonotus obliquus polysaccharide regulates gut microbiota of chronic pancreatitis in mice
Erinacine A-enriched Hericium erinaceus mycelium ameliorates Alzheimer’s disease-related pathologies in APPswe/PS1dE9 transgenic mice
Medicinal mushrooms are multicomponent mixtures (MOCSs). They consist of a large number of individual compounds, each with different chemical structures, functions, and possible pharmacological activities. In contrast to the activity of an isolated pure substance, the effects of the individual substances in a mushroom or its extracts can influence each other; they can strengthen, weaken, or complement each other. This results in both advantages and disadvantages for the use of either a pure substance or a multicomponent mixture.
2024
Population aging has led to an increased interest in various dietary supplements in order to preserve cognitive function. The aim of our study was to examine the effects of Hericium erinaceus supplementation (HE) on cognitive function and serum levels of Brain-Derived Neurotrophic Factor (BDNF) and Neuropeptide Y (NPY). An 8-week double-blind comparative study involved 33 subjects, randomly assigned to a HE group and a placebo (P) group.
2024
Though microdosing psychedelics has become increasingly popular, its long-term effects on cardiac health remain unknown. Microdosing most commonly involves ingesting sub-threshold doses of lysergic acid diethylamide (LSD), psilocybin, or other psychedelic drugs 2–4 times a week for at least several weeks, but potentially months or years.
2024
The traditional medicinal mushroom Hericium erinaceus is known for enhancing peripheral nerve regeneration through targeting nerve growth factor (NGF) neurotrophic activity. Here, we purified and identified biologically new active compounds from H. erinaceus, based on their ability to promote neurite outgrowth in hippocampal neurons. N-de phenylethyl isohericerin (NDPIH), an isoindoline compound from this mushroom, together with its hydrophobic derivative hericene A, were highly potent in promoting extensive axon outgrowth and neurite branching in cultured hippocampal neurons even in the absence of serum, demonstrating potent neurotrophic activity.
2023
Erinacines derived from Hericium erinaceus have been shown to possess various health benefits including neuroprotective effect against neurodegenerative diseases, yet the underlying mechanism remains unknown. Here we found that erinacine S enhances neurite outgrowth in a cell autonomous fashion. It promotes post-injury axon regeneration of PNS neurons and enhances regeneration on inhibitory substrates of CNS neurons.
2023
High glucose can lead to toxicity on islet beta cells. The protective effects of a novel Lentinus edodes mycelia polysaccharide (LMP) on INS-1 cells damaged by glucose were investigated. Cell viability, lactate dehydrogenase (LDH) release, cell apoptosis, intracellular reactive oxygen species (ROS), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content were detected. P38 MAPK, JNKand NF-kappaB pathways were analyzed to reveal the inhibitory mechanism of LMP on glucose-induced INS-1 cells toxicity. The results showed that LMP could decrease cellular oxidative stress, reduce intracellular ROS levels, decrease MDA content and increase SOD activity. Furthermore, the glucose-induced cell apoptosis in cells were inhibited by regulating the expression of Bax, Bcl-2, cleaved caspase3 and cleaved caspase1.
2019
In Alzheimer’s disease (AD), beta-amyloid (Abeta) protein toxicity increases the formation of reactive oxygen species (ROS) and intracellular calcium levels, resulting in neuronal dysfunction, neurodegenerative disorders, and cell death. Cordycepin is a derivative of the nucleoside adenosine; also, it is speculated to exert neuroprotective effects against Abeta-induced oxidative toxicity in hippocampal neurons. In the present study, the fluorescence detection method and whole-cell patch-clamp recordings were used to study the neuroprotective effects against Abeta-induced toxicity in the primary hippocampal cultured neurons. The results revealed that Abeta25-35 toxicity causes increased cellular ROS production and abnormal calcium homeostasis in hippocampal neurons. Moreover, Abeta25-35-induced cytotoxicity led to a series of downstream events, including the activation of acetylcholinesterase, increased p-Tau expression, and increased apoptosis.
2018
Research on the availability of lovastatin in different mushroom species, mechanism of control of diseases like hypercholesterolemia and their drug efficacy are limited. Therefore, the present investigation is focused on quantitative and qualitative analysis of lovastatin from different highly preferred edible oyster mushrooms species by the consumers. The study was carried out for the determination of lovastatin content from different species of mushroom like, Pleurotus ostreatus (grey), Hypsizygus ulmarius (white) and Agaricus djamor (pink) under different culture conditions like Solid State Fermentation (SSF), Submerged Fermentation (SMF) and in the powder of dried mushroom of P. ostreatus as well.
2017
Polysaccharide is efficient in attenuation of metabolic ailments and modulation of gut microbiota as prebiotics. The therapeutic effect of Inonotus obliquus polysaccharide (IOP) on chronic pancreatitis (CP) in mice has been validated in our previous study. However, it is not clear whether IOP is conducive to maintaining the homeostasis between gut microbiota and host. The aim of this study is to testify the potential effects of IOP on gut microbiota composition and diversity in mice with CP. The changes in glutathione peroxidase (GSH-PX), total antioxidant capacity (TAOC), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), lipase and trypsin levels were measured by commercial assay kits, meanwhile the gut microbiota composition and diversity were analyzed by high throughput sequencing.
2017
The fruiting body of Hericium erinaceus has been demonstrated to possess anti-dementia activity in mouse model of Alzheimer’s disease and people with mild cognitive impairment. However, the therapeutic potential of Hericium erinaceus mycelia on Alzheimer’s disease remains unclear. In this study, the effects of erinacine A-enriched Hericium erinaceus mycelia (HE-My) on the pathological changes in APPswe/PS1dE9 transgenic mouse model of Alzheimer’s disease are studied. RESULTS: After a 30 day oral administration to 5 month-old female APPswe/PS1dE9 transgenic mice, we found that HE-My and its ethanol extracts (HE-Et) attenuated cerebral Abeta plaque burden. It’s worth noting that the attenuated portion of a plaque is the non-compact structure.
2016
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"This post literally changed my life. Wow."
Josh Shearer on 01/30/2024
"Testing comments. This is an interesting piece. I would like to collaborate on a further posts."
Josh Shearer on 01/10/2024