Search Results (43)

This narrative review proposes the ‘Brain Health Triad’ as a novel integrative framework for neurorehabilitation and cognitive enhancement, built upon three interdependent biological pillars: neurostimulation, neurotrophy, and neuroprotection. We illustrate how the synergistic interplay between a ‘core triad’ composed of Hericium erinaceus, Bacopa monnieri, and L-Theanine targets these pillars with high specificity. Hericium erinaceus fosters neurotrophy by inducing Nerve Growth Factor (NGF) and Brain-derived neurotrophic factor (BDNF) synthesis through erinacines and hericenones; Bacopa monnieri complements this by enhancing neurostimulation and synaptic plasticity via bacosides; and L-Theanine regulates neurotransmitter balance and alpha-wave activity to stabilize the neural signaling environment. This core architecture is further reinforced by adjunctive nootropic clusters—including withanolides, ginkgolides, citicoline, cordycepin, macamides, and fulvic acid—which provide essential support for mitochondrial resilience and the mitigation of amyloid-β and tau toxicities. By synthesizing molecular evidence from the BDNF/TrkB/CREB signaling axis and the Nrf2/NF-κB homeostatic switch, we demonstrate that this multi-target strategy offers a more robust path to neuronal resilience than traditional single-target approaches. We conclude that this integrated model provides a solid framework for future clinical applications in the management of age-related cognitive decline and neurodegenerative diseases. Full article

Chronic neuroinflammation driven by microglial activation is a pathological hallmark of neurodegenerative diseases, and the NF-$\kappa$B/iNOS signaling axis plays a central role in propagating this damage. NF-$\kappa$B-mediated iNOS transcription generates excessive nitric oxide, causing oxidative neuronal injury. The medicinal mushroom Hericium erinaceus produces cyathane diterpenoid erinacines and isoindolinone erinacerins, both reported to attenuate neuroinflammation; however, the molecular basis of their interactions with iNOS and NF-$\kappa$B remains poorly characterized. We screened 21 erinacerins and 18 erinacines against both targets using validated molecular docking, then subjected top-ranked candidates and negative controls to 100 ns molecular dynamics simulations, MM-PBSA binding free energy calculations (±SEM), per-residue energy decomposition, backbone RMSD, and ligand–protein minimum distance analyses, with quercetin as reference. The analysis revealed scaffold-dependent target selectivity: erinacerins exhibited preferential stability with iNOS (erinacerin L: RMSD 0.185 nm), whereas erinacines formed more stable complexes with NF-$\kappa$B (erinacines G and J: RMSD < 0.36 nm). Minimum-distance monitoring confirmed that the elevated ligand RMSD in iNOS predominantly reflected surface relocation rather than dissociation. Erinacine S emerged as the most promising dual-target candidate ($\Delta G_{bind}$: −24.31 ± 0.16 and −14.24 ± 0.11 kcal/mol for iNOS and NF-$\kappa$B, respectively), over twofold stronger than quercetin for iNOS. Negative controls revealed that docking-based ranking was target-dependent in its discriminative capacity, underscoring the need for MD-based refinement. These results identify erinacine S as a priority candidate for experimental validation. Full article

This study describes a single-laboratory validation of an ultra-high-performance liquid chromatographic (UHPLC) method for the determination of key compounds like hericenones, hericenes, erinacines, and ergosterol in Hericium erinaceus (H. erinaceus, Lion’s Mane) raw materials and finished products. The expanding market for Hericium erinaceus (Lion’s Mane) has increased the need for practical, routine-ready analytical methods that can quantify characteristic marker compounds and strengthen quality control across both raw materials and finished products. In this study, an ultra-high-performance liquid chromatographic (UHPLC) separation method was developed for the determination of hericenones, hericenes, erinacines, and ergosterol in Hericium erinaceus raw materials and finished products. Under the optimized conditions, the major target analytes—hericenones, hericenes, erinacine A, and ergosterol—were fully resolved (R_s > 1.5) within 38 min using an HSS T3 column at 30 °C. All the peaks in the LC chromatogram of Hericium erinaceus samples and standard solutions were structurally confirmed by LC–UV-MS/MS based on the possible mass spectra. The quantitative calibration curves were linear, covering a range of 10–300 μg/mL for hericenone C, D and E, and hericene A, D and C; 3–100 μg/mL for deacylhericenone and deacylhericene; 1–50 μg/mL for erinacine A, and 5–200 μg/mL for ergosterol. Limits of quantification (LOQs) for hericenone C, D, and E and for hericene A, D, and C were approximately 9.263, 4.545, 4.650, 1.854, 10.72, and 11.18 µg/mL, respectively, while LOQs for deacylhericenone and deacylhericene were 1.083 and 2.109 µg/mL. Erinacine A and ergosterol showed LOQs of 0.642 and 8.352 µg/mL, respectively. The recovery of ergosterol was evaluated for the method at two different levels: 91.6~93.9% for 0.2% spiking and 93.0~102.6% for 0.08% spiking. The method was successfully validated, demonstrating inter-day Relative Standard Deviation (RSD) values between 1.1% and 5.7% for detected analytes across diverse matrices. This validated method provides a consistent quantification of hericenones, hericenes, erinacine A, and ergosterol across a range of commercial products and raw Hericium erinaceus materials, providing a sensitive and reliable tool for product characterization and quality control. This method provides QC laboratories with a robust, UV-based tool for standardized product characterization without requiring mass spectrometry. Full article

Hericium erinaceus (H. erinaceus), a medicinal mushroom, is a source of bioactive compounds with demonstrated neuroprotective potential. This activity is primarily attributed to two distinct classes of compounds: erinacines from the mycelium, which potently induce the synthesis of neurotrophins, protein growth factors essential for neuronal survival and health, and hericenones from the fruiting body, which subsequently appear to enhance or potentiate neurotrophin-activated signaling pathways. Preclinical evidence substantiates their ability to enhance neurotrophin levels, particularly Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), and activate their cognate Trk receptors. Activation of these pathways, including PI3K/AKT/mTOR and MAPK/ERK, converges on transcription factors such as CREB, promoting neuronal survival, neurite outgrowth, and synaptic plasticity. However, the precise molecular mechanisms linking these small molecules to the complex orchestration of neurotrophic gene expression remain incompletely defined. This review synthesizes current knowledge of the neurotrophic pharmacology of H. erinaceus bioactives and proposes a novel framework suggesting that non-coding RNAs (ncRNAs) play a key regulatory role. We hypothesize that hericenones and erinacines modulate key transcriptional hubs, such as CREB, Nrf2, and NF-κB, which in turn regulate the expression of specific ncRNAs (e.g., miR-132, miR-146a) known to control neurogenesis, synaptogenesis, oxidative stress, and neuroinflammation. This ncRNA-mediated mechanism may represent an un-explored axis that explains the pleiotropic neuroprotective effects of these compounds. We critically appraise the existing preclinical evidence, identify significant methodological limitations and translational gaps, and propose a structured research roadmap to test these ncRNA-centric hypotheses, aiming to accelerate the rational development of H. erinaceus-derived compounds for neurodegenerative diseases. Full article

Background/Objective: Current treatments for peripheral nerve injury (PNI) lack robust evidence to suggest complete recovery; hence, alternative therapeutics offer new opportunities to develop more effective protocols. Mushroom species and their related components are considered potential candidates for peripheral nerve repair, but their specific effects and underlying mechanisms are not fully understood. This systematic review presents the available evidence on the use of mushroom species for PNI therapy, including the bioactive components and mechanisms of action. Methodology: A comprehensive literature search in three databases (PubMed, Scopus, and Google Scholar) led to the synthesis of 11 records published between 2010 and 2024. Qualitative analysis revealed the neuroregenerative potential of four mushrooms: Amanita muscaria (n = 2), Hericium erinaceus (n = 5), Lignosus rhinocerotis (n = 3), and Flammulina velutipes (n = 1), with aqueous extracts as the most common type of ingredients used (n = 4) relative to specific components such as muscimol, polysaccharide, Erinacine S, and nerve-guided conduits (NGCs). Results: These mushroom-derived treatments enhanced the migration of Schwann cells mainly via the FGF-2 signalling and MAPK pathway. In vivo studies also revealed the ability of H. erinaceus, A. muscaria, and L. rhinocerotis to promote peripheral nerve repair and functional recovery, with evidence suggesting the role of neurotrophic factors, anti-apoptotic signalling, and pro-inflammatory substances. H. erinaceus was identified as the most promising for potential clinical applications, given the stronger evidence-based data and its relatively safer components compared to A. muscuria and other mushroom species. Conclusions: Despite presenting the potential use of mushrooms in managing PNIs, the existing approaches need to be subjected to clinical research to accelerate the development of future therapeutics and preventive measures for PNIs. Full article

Erinacine A, a cyathane diterpenoid derived from the medicinal and edible fungus Hericium erinaceus, is increasingly recognized for its potent neurotrophic and neuroprotective properties. It demonstrates significant therapeutic promise for neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease, primarily by stimulating the synthesis of nerve growth factor (NGF). However, the clinical applicability of erinacine A is currently restricted by its low yield from natural sources and high production costs. This challenge has spurred significant research focused on optimizing its production. This review provides a comprehensive overview of the current advancements in the fermentation-based preparation of erinacine A, including both liquid and solid-state cultivation techniques. Furthermore, we summarize its diverse biological activities, spanning neuroprotection, anticancer, and anti-inflammatory effects, and detail the recent discoveries elucidating its complex biosynthetic pathway. This consolidated overview offers insights into strategies for enhancing its production and supports its ongoing development as a therapeutic agent. Full article

Over the years, macromycete fungi have been used as a source of food, part of religious rites and rituals, and as a medicinal remedy. Species with strong health-promoting potential include Hericium erinaceus, Cordyceps militaris, Ganoderma lucidum, Pleurotus ostreatus, Flammulina velutipes, and Inonotus obliquus. These species contain many bioactive compounds, including β-glucans, endo- and exogenous amino acids, polyphenols, terpenoids, sterols, B vitamins, minerals, and lovastatin. The level of some biologically active substances is species-specific, e.g., hericenones and erinacines, which have neuroprotective properties, and supporting the production of nerve growth factor in the brain for Hericium erinaceus. Due to their high health-promoting potential, mushrooms and substances isolated from them have found applications in livestock nutrition, improving their welfare and productivity. This phenomenon may be of particular importance in the nutrition of laying hens and broiler chickens, where an increase in pathogen resistance to antibiotics has been observed in recent years. Gallus gallus domesticus is a key farm animal for meat and egg production, so the search for new compounds to support bird health is important for food safety. Studies conducted to date indicate that feed supplementation with mushrooms has a beneficial effect on, among other things, bird weight gain; bone mineralisation; and meat and egg quality, including the lipid profile and protein content and shell thickness, and promotes the development of beneficial microbiota, thereby increasing immunity. Full article

The mycelia of Hericium erinaceus contain neuroprotective cyathane diterpenoids (e.g., erinacine A). There is evidence that cultivation of submerged mycelia with surfactants increases glucose uptake and biomass, but the impact on erinacine production is unknown. Here, we tested the impact of glucose and polysorbate 80 on the mycelial erinacine profiles of five Hericium strains cultivated under submergence, including those of Hericium erinaceus, Hericium americanum, and Hericium coralloides. Metabolite profiling confirmed that mycelial extracts contained 13% to 91% of the erinacines A, C and P in additive-free cultures of all strains, with the remainder secreted to the culture medium. Overall, erinacine P production was several orders of magnitude greater than that of the other erinacines, except for H. erinaceus (DAOMC 251029), where erinacine C was most evident. H. coralloides (DAOMC 251017) produced the greatest concentrations of erinacines A and P. For the most part mycelial erinacine concentrations were reduced in cultures co-supplemented with glucose and polysorbate 80. This treatment caused an 83–100% reduction in the concentrations of erinacines A, C, and P in the mycelial extracts of most strains. By contrast, there was evidence that glucose and polysorbate 80 had no effect on erinacine A production within mycelia of H. americanum, and erinacine P concentrations in H. erinaceus (DAOMC 251029) and H. americanum (DAOMC 251011). In most strains, the secretion of erinacines to the culture medium declined with glucose and polysorbate 80. Conversely, these additives increased the concentrations of erinacines C and P in the culture medium filtrate of H. americanum (DAOMC 21467) and yielded more secreted erinacine P in H. erinaceus (DAOMC 251029). The information provides feasible strategies to produce mycelia with unique erinacine profiles including those rich in erinacine P. Full article

The use of plastic products has increased, leading to higher levels of plastic pollution, and it is becoming a major public health concern. Health risks—especially those related to reproductive system dysfunction caused by polystyrene microplastics (PS-MPs)—are emerging issues that require urgent attention. This study aimed to investigate the effects of erinacine A-enriched Hericium erinaceus mycelium (HE) on high-fat-diet- and PS-MP-induced reproductive system dysfunction in male rats. Reproductive dysfunction was induced by administering a high-fat diet followed by exposure to PS-MPs for six weeks. The results showed that HE treatment significantly reduced nitric oxide levels and enhanced glutathione peroxidase activity. Furthermore, HE supplementation significantly downregulated pro-inflammatory cytokines such as interleukin (IL)-6 and IL-1β. Additionally, HE treatment significantly increased Kiss1 concentration, upregulated follicle-stimulating hormone and testosterone levels, reduced the area of the seminiferous tubule lumen, and prevented a reduction in epithelial thickness. HE treatment also significantly increased sperm count and reduced sperm abnormalities. Based on these findings, HE supplementation helps prevent reproductive system dysfunction by reducing oxidative stress and pro-inflammatory cytokines. Therefore, erinacine A-enriched H. erinaceus mycelium could be considered a potential food supplement or functional food ingredient for the treatment of reproductive or testicular dysfunction. Full article

Hongqujiu, one of the three principal varieties of yellow wine, is a traditional fermented beverage originating from China that employs Hongqu as the fermentation agent. In this study, an untargeted metabolomics approach based on gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS) was applied to systematically analyze the volatile compounds (VOCs) and non-volatile compounds (NVCs) in Hongqujiu across different aging years for the first time. The analysis identified a total of 262 VOCs and 2564 NVCs in samples of Hongqujiu aged for six distinct years. Based on metabolic differences, the samples were categorized into two groups: the low-year group (5-year, 6-year) and the high-year group (8-year, 10-year, 15-year, 20-year). Nineteen VOCs (e.g., 4-amino-butyric acid and diethanolamine) and thirty NVCs (e.g., palmitoylethanolamide and erinacine D) were identified as key differential metabolites distinguishing the low-year group from the high-year group. The higher-year group is enriched with a variety of substances with different flavors or biological activities, such as sugar derivatives, amino acids and their complexes, organic acids and their intermediate metabolites, steroids and terpenoid compounds, lipids and their derivatives, nitrogen-containing heterocycles, and aromatic compounds. The accumulation of these substances not only shapes the unique and rich flavor characteristics of aged red rice wine (such as the caramel aroma and umami peptide flavor), but also endows red rice wine with potential health benefits due to the physiological regulatory functions of some active ingredients. This study contributes to a deeper understanding of the composition and dynamic variations in metabolites in Hongqujiu, offering a scientific foundation for identifying aged Hongqujiu and conducting further research to enhance its quality. Full article

Hericium erinaceus, commonly known as lion’s mane mushroom, has gained increasing scientific interest due to its rich composition of bioactive compounds and diverse health-promoting properties. This narrative review provides a comprehensive overview of the nutritional and therapeutic potential of H. erinaceus, with a particular focus on its anti-inflammatory, antioxidant, and antimicrobial activities. A structured literature search was performed using databases such as PubMed, Scopus, Science Direct, Web of Science, Science Direct, and Google Scholar. Studies published in the last two decades focusing on H. erinaceus’ bioactive compounds were included. The chemical composition of H. erinaceus includes polysaccharides, terpenoids (hericenones and erinacines), and phenolic compounds, which exhibit potent antioxidant effects by scavenging reactive oxygen species (ROS) and inducing endogenous antioxidant enzymes. Additionally, H. erinaceus shows promising antimicrobial activity against bacterial and fungal pathogens, with potential applications in combating antibiotic-resistant infections. The mushroom’s capacity to stimulate nerve growth factor (NGF) synthesis has highlighted its potential in preventing and managing neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. Advances in biotechnological methods, including optimized cultivation techniques and novel extraction methods, may further enhance the bioavailability and pharmacological effects of H. erinaceus. Despite promising findings, clinical validation remains limited. Future research should prioritize large-scale clinical trials, the standardization of extraction methods, and the elucidation of pharmacokinetics to facilitate its integration into evidence-based medicine. The potential of H. erinaceus as a functional food, nutraceutical, and adjunct therapeutic agent highlights the need for interdisciplinary collaboration between researchers, clinicians, and regulatory bodies. Full article

A simple and robust two-dimensional chromatographic fractionation protocol for the isolation of the neuroprotective compound erinacine A from Hericium erinaceus is proposed. This production platform yielded 19.4 mg of erinacine A from approximately 130 g of mushroom material, with a chromatographic purity of 97.4%. The procedure includes extraction, concentration, fractionation, purification, and characterisation of the bioactive compound. The crude H. erinaceus extract was fractionated in the first dimension by normal-phase flash chromatography, and the fraction containing erinacine A was further purified in the second dimension by semi-preparative reversed-phase chromatography. This strategy utilises the orthogonality of the two chromatographic modes to effectively eliminate difficult impurities, including structural isomers and analogues of erinacine A. Complementary analytical approaches such as high-performance thin-layer chromatography (HPTLC) and high-performance liquid chromatography with ultraviolet and tandem mass spectrometric detection (HPLC–UV–MS/MS) were employed to unambiguously confirm erinacine A in the isolated fractions, while HPLC with a charged aerosol detector (CAD) was used to determine its purity. Given the limited commercial availability and the high price of erinacine A, the described method offers a straightforward and cost-effective alternative to obtain this valuable compound for further research and applications. Full article

Spinocerebellar ataxia type 3 (SCA3), caused by the abnormal expansion of polyglutamine (polyQ) in the ataxin-3 protein, is one of the inherited polyQ neurodegenerative diseases that share similar genetic and molecular features. Mutant polyQ-expanded ataxin-3 protein is prone to aggregation in affected neurons and is predominantly degraded by autophagy, which is beneficial for neurodegenerative disease treatment. Not only does mutant polyQ-expanded ataxin-3 increase susceptibility to oxidative cytotoxicity, but it also hampers antioxidant potency in neuronal cells. Nuclear factor erythroid-derived 2-like 2 (Nrf2), a master transcription factor that controls antioxidant and detoxification gene expression, plays a crucial role in neuroprotection in SCA3 and other neurodegenerative diseases. The present data showed that treatment with erinacine A-enriched Hericium erinaceus mycelium ethanol extract (HEME) extended longevity and improved locomotor activity in ELAV-SCA3tr-Q78 transgenic Drosophila. Moreover, HEME treatment enhanced antioxidant potency and autophagy, which, in turn, corrected levels of mutant polyQ-expanded ataxin-3 and restrained protein aggregation in both cell and Drosophila models of SCA3. Markedly, HEME increased the activation of Nrf2. Silencing Nrf2 protein expression negated most of the promising effects of HEME on SK-N-SH-MJD78 cells, highlighting the critical role of increased Nrf2 activation in the efficacy of HEME treatment. These findings suggest that HEME has therapeutic potential in SCA3 by enhancing autophagic and Nrf2-mediated antioxidant pathways, which may also influence neurodegenerative progression in other polyQ diseases. Full article

In recent years, research on mushrooms belonging to the Hericium genus has attracted considerable attention due to their unique appearance and well-known medicinal properties. These mushrooms are abundant in bioactive chemicals like polysaccharides, hericenones, erinacines, hericerins, resorcinols, steroids, mono- and diterpenes, and corallocins, alongside essential nutrients. These compounds demonstrate beneficial bioactivities which are related to various physiological systems of the body, including the digestive, immune, and nervous systems. Extensive research has been conducted on the isolation and identification of numerous bioactive chemicals, and both in vitro and in vivo studies have confirmed their antimicrobial, antioxidant, immunomodulatory, antidiabetic, anticholesterolemic, anticancer, and neuroprotective properties. Therefore, this review aims to provide a comprehensive summary of the latest scientific literature on the chemical composition and secondary metabolites profile of Hericium spp. through an introduction to their chemical characteristics, speculated biosynthesis pathways for key chemical families, potential toxicological aspects, and a detailed description of the recent updates regarding the bioactivity of these metabolites. Full article

Hericium erinaceus has long been favored for its remarkable nutritional and health-promoting benefits, and erinacine A is the key component responsible for the neuroprotective properties of H. erinaceus. Establishing an efficient method for separating erinacine A from H. erinaceus and screening the erinacine A-enriched strains is crucial to maximizing its benefits. Herein, we first reported that high-speed counter current chromatography (HSCCC) is an effective method for separating high-purity erinacine A. Using a two-phase solvent system composed of n-hexane/ethyl acetate/methanol/water (4.5:5:4.5:5, v/v/v/v), erinacine A with a purity of over 95% was separated. Then, we evaluated the content and yield of erinacine A in the liquid-fermented mycelia of Hericium germplasms. Both the content and yield of erinacine A varied greatly among the surveyed strains. The significant effect of the strain on the erinacine A content and yield was revealed by an analysis of variance. The highest erinacine A content and yield were observed in the mycelia of a wild strain HeG, reaching 42.16 mg/g and 358.78 mg/L, which is superior to the current highest outcomes achieved using submerged cultivation. The isolation method established and the strains screened in this study can be beneficial for the scaling up of erinacine A extraction and nutraceutical development to industrial levels. Full article