Lion's Mane Mushroom

BACKGROUND: Given the bioactive properties and limited work to date, Hericium erinaceus (Lion's mane) shows promise in improving cognitive function and mood. However, much of the human research has concentrated on chronic supplementation in cognitively compromised cohorts. OBJECTIVE: The current pilot study investigated the acute and chronic (28-day) cognitive and mood-enhancing effects of Hericium erinaceus in a healthy, young adult cohort. DESIGN: This randomized, double-blind, placebo-controlled, parallel-groups design investigated the acute (60 min post dose) and chronic (28-day intervention) effects of 1.8 g Hericium erinaceus in 41 healthy adults aged 18-45 years. RESULTS: Analysis revealed that following a single dose of Hericium erinaceus, participants performed quicker on the Stroop task (p = 0.005) at 60 min post dose. A trend towards reduced subjective stress was observed following 28-day supplementation (p = 0.051). CONCLUSIONS: The findings tentatively suggest that Hericium erinaceus may improve speed of performance and reduce subjective stress in healthy, young adults. However, null and limited negative findings were also observed. Given the small sample size, these findings should be interpreted with caution. Further investigation in larger sample sizes is crucial, however the findings of this trial offer a promising avenue of interest.

This article reviews mushrooms with anti-breast cancer activity. The mushrooms covered which are better known include the following: button mushroom Agaricus bisporus, Brazilian mushroom Agaricus blazei, Amauroderma rugosum, stout camphor fungus Antrodia camphorata, Jew's ear (black) fungus or black wood ear fungus Auricularia auricula-judae, reishi mushroom or Lingzhi Ganoderma lucidum, Ganoderma sinense, maitake mushroom or sheep's head mushroom Grifola frondosa, lion's mane mushroom or monkey head mushroom Hericium erinaceum, brown beech mushroom Hypsizigus marmoreus, sulfur polypore mushroom Laetiporus sulphureus, Lentinula edodes (shiitake mushroom), Phellinus linteus (Japanese "meshimakobu," Chinese "song gen," Korean "sanghwang," American "black hoof mushroom"), abalone mushroom Pleurotus abalonus, king oyster mushroom Pleurotus eryngii, oyster mushroom Pleurotus ostreatus, tuckahoe or Fu Ling Poria cocos, and split gill mushroom Schizophyllum commune. Antineoplastic effectiveness in human clinical trials and mechanism of anticancer action have been reported for Antrodia camphorata, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa, and Lentinula edodes.

Low mental energy can contribute to decreased productivity, altered life balance, decreased physical performance, and ultimately affect quality of life. As such, there is a great demand for food and beverage products that positively impact mental energy. Numerous products claim to alter mental energy making continued review of the scientific evidence critical. The objective of this study was to conduct a scoping review of randomized controlled trials to evaluate the effect of 18 dietary ingredients on mental energy outcomes in adults without severe disease. Methods: A literature search, completed using PubMed, resulted in the identification of 2261 articles, 190 of which met eligibility from initial abstract review. Full-text review was completed on the 190 studies which resulted in 101 articles that fully met eligibility for inclusion in this study. The search strategy for two ingredients did not yield any eligible studies, leaving studies for 16 ingredients that were extracted and summarized by reported significantly improved outcomes for cognition, mood and perceived feelings, and sleep assessments. The preliminary results for several dietary ingredients directionally suggested a mental energy benefit (≥20% of outcomes), including ashwagandha, chamomile, dark chocolate, ginseng, green tea, lavender, lion's mane mushroom, maca, tart cherries, turmeric, and valerian root. The results of this scoping review suggest that of the 16 dietary ingredients reviewed, 11 may be promising for further exploration on their potential benefits in supporting mental energy. Given consumer demand and market growth for food and beverage products that positively impact mental energy; continued efforts in assessment method alignment and additional evaluation in well-designed trials is warranted.KEY TEACHING POINTSOf the 16 dietary ingredients reviewed, 11 (ashwagandha, chamomile, dark chocolate, ginseng, green tea, lavender, lion's mane mushroom, maca, melatonin foods, turmeric, and valerian root) may be promising for further exploration on their potential mental energy benefits.Dark chocolate, ginseng, ashwagandha, and lion's mane mushroom were the most promising ingredients for f

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.

Fungal polysaccharides have attracted considerable scholarly interest due to their potential as prebiotics, with the ability to modulate gut microbiota and enhance host health. Despite increasing recognition, the precise effects of composite polysaccharides from various fungal species on gut microbial composition and metabolic activity remain inadequately understood. This study sought to investigate the digestibility and fermentation characteristics of composite polysaccharides derived from Lyophyllum decastes (LDUP) and Hericium erinaceus (HEUP), combined at ratios of 1:1, 1:2, and 2:1 (LDHE1_1, LDHE1_2, and LDHE2_1). In vitro simulated gastrointestinal digestion and fermentation assays were conducted to assess pH variations, short-chain fatty acid (SCFA) production, and shifts in microbial communities. The findings revealed that the LDHE1_1 formulation exhibited the most significant capacity to reduce pH and produce SCFAs, particularly propionic and butyric acids. Furthermore, the LDUP and LDHE2_1 groups favored increased acetic acid production. Importantly, these composite polysaccharides substantially enhanced gut microbial diversity, with distinct formulations promoting specific bacterial taxa. The LDUP and LDHE1_1 groups increased Firmicutes and decreased Bacteroidota, while HEUP, LDHE1_2, and LDHE2_1 groups exhibited the reverse. At the genus level, the LDHE1_1 boosted Parabacteroides, and LDHE2_1 increased Phascolarctobacterium, Akkermansia, and Oscillibacter. Both the LDUP and HEUP notably raised Alistipes levels, and all polysaccharide groups suppressed potential pathogens such as Klebsiella and Escherichia-Shigella. This study provides new insights into how specific fungal polysaccharide combinations can modulate gut microbiota composition and metabolism, contributing to the design of targeted prebiotic formulations and functional foods. © 2026 Institute of Food Technologists.

The cultivation of Hericium erinaceus in China accounts for about 85% of the global supply. Its decentralized production systems have developed across diverse climate zones, leading to distinct, location-specific practices recorded in local technical standards. This scoping review synthesizes these empirical protocols from five agro-climatic regions. It illustrates how adaptive strategies such as cold-tolerant strains in the northeast and market-driven precision in the subtropics are associated with yield stability. These practices reflect two interconnected forms of diversity. One is the diversity of cultivation systems themselves, from forest-based methods to industrial-scale production systems. The other is the diversity of locally adapted strains developed for specific environments. We use the Intelligent Germplasm-Cultivation-Processing-Market (GCPM) Integration framework to connect local practices with broader questions of systemic resilience. The evidence draws on field-validated standards, not controlled experiments, reflecting the current state of research. This work presents China's practical knowledge as a reference for designing context-sensitive, climate-resilient cultivation systems elsewhere, suggesting that resilience may depend more on intelligent adaptation to local conditions than on one-size-fits-all solutions.

BACKGROUND: Hericium erinaceus polysaccharides (HEPs) exhibit remarkable immunomodulatory properties but are hampered by poor oral bioavailability. To overcome these limitations, this study developed and optimized HEP-loaded polyethyleneimine (PEI)-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (HEP-PPNPs) as a novel drug delivery system. RESULTS: Following formulation optimization, HEP-PPNPs were successfully prepared using a modified double-emulsion solvent evaporation method, achieving a high encapsulation efficiency of 71.78%. The prepared nanoparticles exhibited a spherical morphology with a mean particle size of 176.4 ± 3.6 nm, a narrow polydispersity index of 0.131 ± 0.005 and a positive zeta potential of +32.8 ± 0.3 mV. Biological assessments on RAW264.7 macrophages showed that HEP-PPNPs significantly enhanced phagocytic activity and promoted the secretion of key immunomodulatory cytokines (TNF-α, IL-6 and IL-4) without cytotoxicity at effective concentrations. Furthermore, HEP-PPNPs markedly upregulated the expression of co-stimulatory molecules CD80 and CD86. The immunoenhancement effect of HEP-PPNPs was significantly superior to that of both free HEPs and unmodified HEP-PLGA nanoparticles. CONCLUSION: The developed HEP-PPNPs system effectively mitigates the pharmacokinetic limitations of native HEPs. The formulation demonstrates favorable physicochemical properties and elicits a stronger immunostimulatory response compared to the non-encapsulated drug and its non-cationic nanoparticle counterpart. This PEI-modified nanoparticle platform represents a promising strategy for enhancing the oral therapeutic efficacy of HEPs. © 2026 Society of Chemical Industry. © 2026 Society of Chemical Industry.

A novel heteropolysaccharide named HEP-S was separated from the mycelium of Hericium erinaceus using hot water extraction. The structure of HEP-S (2.45 × 106 Da) is mainly composed of →4,6)-α-D-Glcp(1→, →2)-α-D-Manp(1→, →4)-α-D-Glcp(1→, →3,6)-β-D-Glcp(1→, T-β-D-Galp(1→, and →4)-β-D-Galp(1→. In addition, we investigated the anti-inflammatory activity and mechanism of HEP-S in lipopolysaccharide-stimulated RAW264.7 cells. HEP-S (20, 40, and 80 µg/mL) could suppress the production of inflammatory cytokines by reducing vital transcription factors in the nuclear factor-κB signaling (NF-κB) pathway. The results showed that HEP-S exhibited notable anti-inflammatory activity on RAW 264.7, demonstrating its potential therapeutic effect on relieving gastritis. © 2026 International Union of Biochemistry and Molecular Biology, Inc.

Erratum in Food Funct. 2026 Oct 19;17(20):9373. doi: 10.1039/d6fo90080a. Bioactive galactans are widely distributed in nature, with some extensively reported for their potential in modulating the gut microbiota and intestinal inflammation. However, the efficacy of different galactans in ameliorating colitis remains unclear. Our study systematically compared the effects of three nonlinear galactans (Hericium erinaceus polysaccharides, HEP; Lycium barbarum polysaccharides, LBP; larch arabinogalactan, LAG) and two linear galactans (agarose, AGR; carrageenan, CGN) on colitis in mice. The results indicated that HEP, LBP and LAG treatments significantly alleviated colitis symptoms, regulated the inflammatory cytokines and improved intestinal barrier function. Notably, they could modulate the gut microbiota by promoting the relative abundance of probiotics such as S24-7, Lactobacillus and Bacteroides, while suppressing the proliferation of pathogenic bacteria like Enterobacteriaceae. In contrast, AGR and CGN showed no significant alleviative effects on most indicators. This study highlights the efficacy of different types of galactans in treating colitis and modulating the gut microbiota, providing a theoretical basis for the development of dietary polysaccharide-based intervention strategies for IBD.

Erinacerins are a group of bioactive heterocyclic organic compounds known as Isoindolin-1-one metabolites with the molecular formula C8H9N, derived from the mycelia or fruiting bodies of the mushroom Hericium erinaceus. They are known for their neuroprotective, anti-inflammatory, and anticancer properties. Erinacerins inhibit the growth of breast, colon, and lung cancer cells; induce apoptosis, prevent angiogenesis, and overcome cancer therapy. Some Erinacerins lack a documented therapeutic target or a mechanism of action. This study aimed to identify therapeutic protein targets for Erinacerins that have been verified to exhibit cytotoxic effects in cancer cell lines. A virtual metabolite screening of Hericium erinaceus was conducted using the MeFSAT database. Following a systematic two-step filtering process, erinacerins meeting an established criterion were selected. A target search was performed based on Erinacerin's structure, leading to the identification of the receptor Multidrug Resistance Protein (MDR)1 or P-glycoprotein (P-gp, ABCB1) as a potential target for Erinacerin S. Results showed a strong binding affinity to the ABCB1 canonical drug-binding pocket, consistently interacting with transmembrane domains (TMs) 7, 9, and 12. Van der Waals forces dominated binding energetics, with PHE343, MET986, and LEU225 as key stabilizing residues. TM9 emerged as a critical pharmacophore region. Structural analyses revealed conformational plasticity in the TM4 and TM6 helices, suggesting an allosteric mechanism. RMSD and Rgyr variations across replicas indicated dynamic ligand-receptor interactions, supporting the potential for bidirectional modulation. This study provides the first evidence supporting Erinacerin S as a potential ABCB1 inhibitor, suggesting its role in overcoming multidrug resistance in cancer therapy.

Chronic neuroinflammation driven by microglial activation is a pathological hallmark of neurodegenerative diseases, and the NF-κB/iNOS signaling axis plays a central role in propagating this damage. NF-κB-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-κB 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-κB (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 (ΔGbind: -24.31 ± 0.16 and -14.24 ± 0.11 kcal/mol for iNOS and NF-κB, 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.

In this study, the Box-Behnken Design (BBD) was adopted to optimize the ultrasound-assisted extraction (UAE) conditions of polyphenols from Hericium erinaceus (H. erinaceus) on the basis of single-factor experiments, with extraction time, solid-liquid ratio and ethanol concentration as the key investigation factors. The optimal extraction parameters were determined as follows: extraction time of 56.85 min, solid-liquid ratio of 1:56.71 g/mL and ethanol concentration of 44.64%, under which the actual yield of the total polyphenol crude extract (TPCE) reached 0.9985 ± 0.03%, which was highly consistent with the theoretical predicted value of 0.9960%, verifying the good fitting degree of the established model. Taking L-ascorbic acid as the positive control, the antioxidant activity of TPCE was evaluated by determining its scavenging capacity against ABTS·+, ·OH and DPPH· free radicals, and the half-maximal effective concentration (EC50) values were measured to be 0.8850, 0.9490 and 4.198 mg/mL, respectively. With acarbose as the reference drug, the inhibitory effects of TPCE on α-amylase and α-glucosidase related to carbohydrate metabolism were assayed, and the corresponding half-maximal inhibitory concentration (IC50) values were 0.0135 and 130.3 mg/mL, respectively. Furthermore, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was employed for the tentative identification of bioactive components in TPCE, and a total of 48 and 64 chemical constituents were characterized in negative and positive ion modes, respectively, providing a chemical basis for the biological activities of TPCE. This study confirmed that UAE is an efficient and feasible technology for extracting polyphenols from H. erinaceus, which lays a theoretical foundation for the development and utilization of its polyphenols, and also provides novel insights into the development of natural functional ingredients and potential therapeutic agents for the intervention of type 2 diabetes. Additionally, the findings further validate edible fungi as a valuable reservoir of natural bioactive substances, with promising application prospects in the researc

Hericium erinaceus is a widely consumed edible mushroom with significant ethnopharmacological value. Nevertheless, the pharmacological understanding of H. erinaceus presenting crucial bioactive compounds, their therapeutic targets, and its benefits across diseases in the form of bioactive-target-disease connectivity is yet to be explored. This study evaluates the antioxidant activity and cytoprotective effects of H. erinaceus extract on V79 fibroblast cells in vitro, to profile its bioactive compounds, and to conduct a network pharmacological analysis to identify key bioactives linked to therapeutic target proteins and diseases. A qualitative analysis identified the existence of tannins, alkaloids, steroids, terpenoids, polysaccharides, and phytosterols. Vibrational infrared spectroscopy confirmed the existence of alkanes, alkenes, alkynes, aromatics, aldehydes, esters, alcohols, aliphatics, and primary amines. Cytoprotective investigation demonstrated that the concentrations (10-25 μg/mL) of the extract preserve 95% cell viability and significant antioxidant properties. Gas chromatography-mass spectrometry analysis of the H. erinaceus extract yielded 49 components. The absorption, distribution, metabolism, excretion, and toxicity (ADMET)-filtered compounds were subjected to target prediction and pathway analysis, which revealed PPARG protein and its signaling pathways were the most significant targets. Further, disease association analysis identified PPARG's links to various diseases, which could benefit from using H. erinaceus. Molecular docking (-6.804 kcal/mol), binding free energy (-42.05 kcal/mol), and dynamic simulations confirmed a strong interaction between PPARG and 2-methyl hexadecanoic acid. These findings underscore the antioxidant and cytoprotective capabilities of H. erinaceus phytochemicals, as well as their potential therapeutic safety and efficacy for further investigation.

Hericium erinaceus is widely recognized for its culinary and medicinal properties. This study evaluates various extraction techniques to optimize total phenolic and polysaccharide fractions in H. erinaceus. The objective was to determine the most suitable method for maximizing both yield and bioactivity of the extracts. We assessed the effectiveness of traditional soaking and ultrasonication for phenolic extraction, alongside hot water extraction, enzyme-assisted extraction, and cold and hot alkaline extraction methods for polysaccharide extraction. GC-MS metabolite profiling indicated that ultrasonic phenolic extraction combined with NaOH-based alkaline extraction was the most effective, yielding the highest polysaccharide content and demonstrating superior antioxidant activity. These findings highlight the efficacy of the extraction technique in isolating bioactive compounds rich in metabolites by reducing the extraction timeline, demonstrating its potential for diverse applications in the nutraceutical industry.

BACKGROUND: Current treatment strategies for symptomatic uncomplicated diverticular disease (SUDD) remain controversial. Nutraceuticals could be potential adjuvant treatments to reduce symptoms and improve Quality of Life (QoL). METHODS: A retrospective analysis of data collected in a real-world clinical setting was performed on SUDD patients with persistent diarrheal symptoms following rifaximin therapy. A synbiotic anti-inflammatory dietary supplement (SADS), containing Lactobacillus rhamnosus GG, Hericium erinaceus, berberine, quercetin, palmitoylethanolamide, and Undaria, was administered daily for one month to evaluate its effectiveness in reducing these symptoms. Outcome measures included daily bowel movement frequency, Abdominal Pain Score, treatment satisfaction, and fecal calprotectin levels, and were evaluated at baseline (T0) and after one month (T1). RESULTS: Data from 54 SUDD patients (mean age: 53.2±11.3 years) were collected. Daily bowel movements significantly decreased after SADS treatment (T1) compared to T0 (2.18±0.8 vs. 3.8±0.7; P<0.001). Abdominal Pain Score also improved significantly (2.59±1.2 vs. 5.81±1.0; P<0.001), with 88.9% of patients reporting moderate-to-high treatment satisfaction. Calprotectin levels decreased significantly following SADS treatment (P<0.001), with positive test results reducing from 100% at T0 to 65% at T1, while negative results increased from 0% to 35%. Significant negative correlations were observed between treatment satisfaction and both abdominal pain scores (r=-0.742; P<0.001) and daily bowel movement frequency (r=-0.516; P<0.001). CONCLUSIONS: This SADS could be considered as a supportive treatment for SUDD patients, potentially alleviating symptoms and improving QoL. Further prospective clinical trials are required to confirm these observations.

This study investigates how Hericium erinaceus powder (HE powder) modulates the gluten network and influences steamed bread quality. HE powder altered water distribution and mobility, consistent with changes in dough thermo-mechanical behavior, pasting properties, and crumb microstructure. Protein analyses indicated enhanced disulfide bonding and hydrophobic interactions. UV-Vis, intrinsic fluorescence, and FT-IR further suggested a hydrophobic microenvironment around aromatic residues, accompanied by an increased β-sheet proportion and a reduced random coil fraction. At higher substitution levels, product performance deteriorated, with hardness increasing from 696.67 to 2116.33 g and specific volume decreasing from 2.54 to 1.77 mL/g. Starch digestibility was modulated at lower substitution levels, reflected by reduced rapidly digestible starch (RDS), while antioxidant activity increased, with DPPH radical scavenging reaching approximately 45%. © 2026 The Authors.

Lion's Mane mushroom (Hericium erinaceus) holds a significant place in traditional Chinese medicine (TCM), valued for centuries for benefiting various internal organs and overall well-being. It is also celebrated as a culinary delicacy in East Asia, prized for its fleshy, meat-like texture and mild, seafood-like flavor. High concentrations of glutamic and aspartic acids generate a pronounced umami taste, enhancing its culinary appeal and supporting its use as a natural flavor enhancer. Nutritionally, it provides dietary fiber, essential minerals, and high protein content, notably in the mycelial biomass (up to 42.5% dry weight), making it especially suitable as a protein source in meat alternative applications. The mushroom's therapeutic potential is rooted in its novel bioactive constituents. Hericenones (in fruiting bodies) and erinacines (in mycelia) are diterpenoids that stimulate nerve growth factor (NGF) synthesis, supporting neuronal function. Furthermore, immunomodulatory β-glucans, antioxidant phenolic compounds, and ergothioneine contribute to its overall health benefits. However, these functional properties are predominantly supported by in vitro and animal studies. Despite growing interest in its medicinal properties, integrated evaluations of the nutritional composition, bioactive profile, and technological potential of H. erinaceus for modern food applications remain limited. By leveraging both its sensory attributes and scientifically validated functional value, H. erinaceus can be incorporated into beverages, staple foods, and meat substitutes. This comprehensive review examines its dual role as a medicinal and culinary mushroom, to hopefully enhance understanding of the mushroom and inspire its future applications in food technology. © 2026 Institute of Food Technologists.

This study aimed to increase the product's soluble dietary fiber (SDF) yield through static magnetic field (SSF)-assisted Hericium erinaceus solid-state fermentation (MSSF) of corn husks. The optimal extraction conditions were met using a response surface methodology, resulting in an increase from 0.33 g/100 g to 15.34 g/100 g in SDF yield. The study also analyzed the kinetic changes induced by SMF during fermentation and the effects of MSSF on the structure and physicochemical properties of SDF. Results demonstrated that SMF treatment enhanced the activity of carboxymethylcellulase and hemicellulase secreted by mycelial growth, accelerating the degradation of insoluble dietary fiber and SDF formation. The MSSF treatment resulted in a looser SDF network structure, reduced molecular weight and particle size, improved crystallinity, thermal stability, and absolute zeta potential. Additionally, the water holding capacity, oil holding capacity, and water swelling capacity of SDF increased by up to 122.18%, 156.70%, and 193.42%, respectively.

BACKGROUND: Peripheral nerve injuries (PNI) frequently result in incomplete functional recovery, creating a significant translational gap despite advances in surgical techniques. While Hericium erinaceus (H. erinaceus), lithium, and vitamin B12 have individually demonstrated promising neuromodulatory and neurotrophic properties -targeting axonal growth, myelination, and neuroprotection - no existing experimental model has investigated their combined synergistic potential. This lack of integrated approach represents a major barrier to developing effective multimodal therapies. HYPOTHESIS: We propose a "triple neuromodulatory axis" hypothesis: that the combined administration of H. erinaceus, lithium, and vitamin B12 will exert a synergistic effect on peripheral nerve regeneration. This synergy is mechanistically driven by the agents' convergence on three vital pathways: neurotrophic signaling (TrkA/ERK), glial modulation (GSK-3β/β-catenin), and metabolic/methylation support. The coordinated action of this axis is hypothesized to ensure simultaneous initiation of axonal growth, rapid Schwann cell proliferation, and sustained myelination. Translational rationale: The convergence of these mechanisms suggests that the triple axis, when tested in appropriate in vivo models of nerve injury, will yield superior functional outcomes (e.g., Sciatic Functional Index) and histological repair (e.g., myelin density and axon count) compared to standard treatments or mono-treatments. CONCLUSION: The triple neuromodulatory axis provides a testable translational framework for designing future multi-arm studies aimed at validating a novel, synergistic pharmacological strategy for enhancing neurorepair in diabetic and post-traumatic neuropathies.

INTRODUCTION: Light represents a major environmental factor influencing the growth, developmental programming, and metabolic regulation of Hericium erinaceus. Different wavelengths differentially affect mycelial development, stress responses, and protein expression, highlighting the complexity of fungal photoregulation. However, the molecular mechanisms and light-responsive regulatory networks in H. erinaceus remain largely unclear, limiting our understanding of how specific light cues shape its proteomic profiles. METHODS: A label-free LC-MS/MS quantitative proteomics approach was employed to investigate the global protein expression profiles of H. erinaceus mycelia growing under different light treatments, including blue, green, red, and RGB qualities, compared to control (darkness). The differentially expressed proteins (DEPs) were subsequently annotated and analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. RESULTS: In this study, a total of 4,618 proteins were identified in H. erinaceus, of which 560 were expressed across all experimental conditions. Comparative proteomic analysis under different light treatments revealed 550-677 DEPs per condition, with the blue-light treatment exhibiting the greatest number of uniquely expressed proteins. Light exposure modulated GO-enriched metabolic, biosynthetic, and enzymatic functions in H. erinaceus. RGB induced the broadest responses, while blue, green, and red produced distinct wavelength-specific regulatory patterns. KEGG pathway analysis showed wavelength-dependent proteomic shifts in H. erinaceus, with RGB inducing the strongest metabolic and signaling responses, while blue, green, and red differentially activated energy, biosynthesis, and regulatory pathways. These results support the molecular-mechanistic approach employed and offer valuable insights into protein expression dynamics and regulatory pathways, while also clarifying how different light qualities influence the developmental processes of H. erinaceus.

Against the backdrop of China's booming edible fungi industry, shortages and price hikes of traditional cultivation substrates have emerged as critical bottlenecks. Meanwhile, the disposal of a large amount of ginger straw produced during the ginger cultivation process is also a major challenge. To address these issues, this study explored ginger straw as an alternative substrate for Pleurotus geesteranus and Hericium erinaceus, focusing on the optimization of substrate formulas and their effects on the nutritional quality of the fungi. Superior strains were first screened, after which the addition ratios of ginger straw (10-40%) were optimized. Commercial characteristics, nutritional components, and safety indicators of the fruiting bodies were determined, and a comprehensive quality evaluation was conducted using the membership function method. Results indicated that excellent strains of both fungi were selected: the optimal ginger straw addition ratio was 15-30% for P. geesteranus and 15% for H. erinaceus. Compared with the conventional cottonseed hull substrate, the optimized formulas significantly increased the biological efficiency (BE) by 9.08-27.1% for P. geesteranus and 9.16% for H. erinaceus. They also improved the contents of key nutrients (e.g., proteins and amino acids), enhanced total antioxidant capacity, and optimized the composition of flavor-contributing amino acids. This study offers a novel approach for the efficient utilization of ginger straw, provides technical and theoretical support for the low-cost and high-quality cultivation of edible fungi, and contributes positively to the development of ecological circular agriculture.

Inflammatory bowel disease (IBD) is a chronic disorder marked by mucosal barrier disruption, immune imbalance, and gut dysbiosis. Polysaccharide-enriched extracts of Hericium erinaceus (HE) have shown anti-colitic effects, but the role of its β-glucan-rich water extract (HE-HW) remains unclear. By investigating a commercially relevant β-glucan-rich extract rather than isolated polysaccharides, this work addresses a key translational gap in HE research. HE-HW, rich in 1,3:1,6-β-glucan (286.4 mg/g), was evaluated using cells and mouse colitis models. In RAW 264.7 macrophages, HE-HW (1-10 μg/mL) suppressed lipopolysaccharide-induced nitric oxide and pro-inflammatory cytokines (IL-6, MCP-1) without cytotoxicity. In DSS-stimulated Caco-2 cells, HE-HW downregulated inflammatory mediators and restored tight junction genes (occludin, ZO-1, MUC2). In DSS-induced colitis mice, oral HE-HW (1 or 5 mg/kg/day) improved disease activity and colon length while normalizing serum and tissue cytokines and immunoglobulins. Histology confirmed reduced mucosal damage, muscle thickening, and collagen accumulation. Microbiome profiling showed HE-HW attenuated DSS-associated enrichment of Erysipelatoclostridium, Faecalibaculum, and Olsenella, suggesting selective remodeling of inflammation-related microbial populations. These findings demonstrate that β-glucan-rich HE-HW protects against colitis by modulating inflammation, reinforcing epithelial integrity, and rebalancing gut microbiota.

Erinacines are a class of cyathane diterpenoids predominantly biosynthesized in the mycelia of the medicinal mushroom Hericium erinaceus, commonly known as Lion’s Mane or Yamabushitake. Recognized as the main constituents responsible for the neurological effects of Hericium species, erinacines exhibit a range of biological properties, including anti-inflammatory, neurotrophic, neurogenic, antidepressant, and anticancer activities, as well as κ-opioid receptor agonist activity. This review provides a detailed analysis of the pharmacological potential of the twenty-three erinacines reported to date, along with their comprehensive nuclear magnetic resonance (NMR) characterization. This work underscores the promise of erinacines as valuable lead compounds for the development of therapeutic agents.

BACKGROUND: The human gut microbiota plays a crucial role in various aspects of health, extending beyond digestion and nutrient absorption. Ganoderma lucidum (Reishi) and Hericium erinaceus (Lion's Mane), traditional medicinal mushrooms, have garnered interest due to their potential to exert positive health effects. The aim of our study was to investigate the molecular impact of Reishi and Lion's Mane on mood regulation through the gut-brain axis. METHODS: We utilized a dynamic simulator of the human intestinal microbial ecosystem (SHIME), followed by HPLC-ESI-QTOF-MS/MS and a series of biochemical and molecular assays, including MTT for cell viability, fluorogenic probes for redox balance (ROS and GSH), and Western blot for protein analysis. RESULTS: Chromatographic analysis confirmed the presence of bioactive compounds in both mushrooms, including triterpenoids (ganoderic acids) and polysaccharides in G. lucidum, as well as hericenones and erinacines in H. erinaceus. We observed concentration-dependent changes in metabolic activity and redox balance due to microbiome cell-free supernatant treatment (M-CFSs). M-CFSs also influenced the Nrf2 pathway and activated heat shock proteins, which may confer neuroprotective effects. Notably, M-CFSs upregulated neurotrophic factors such as BDNF, CDNF, and MANF, crucial for neuronal function. Our study revealed alterations in intracellular signaling cascades, most notably the CREB/BDNF pathway. Moreover, the Akt/mTOR and ERK1/2 showed no significant changes, while Akt/GSK3α/β displayed only partial modifications. The overlapping effects of synaptic activity and activation of the gut-brain axis appear to contribute to mood enhancement. CONCLUSIONS: These pilot findings suggest a potential role for G. lucidum and H. erinaceus in mood disorder regulation through multifaceted mechanisms involving the gut microbiota. The study underscores the importance of understanding the synergistic interactions between medicinal fungi, gut microbiota, and neural processes to develop novel or preventive strategies for mental health disorders.

Hericium erinaceus is a valuable mushroom known for its strong bioactive properties. It shows promising potential as an excellent neuroprotective agent, capable of stimulating nerve growth factor release, regulating inflammatory processes, reducing oxidative stress, and safeguarding nerve cells from apoptosis. The active compounds in the mushroom, such as erinacines and hericenones, have been the subject of research, providing evidence of their neuroprotective effects. Further research and standardization processes for dietary supplements focused on H. erinaceus are essential to ensuring effectiveness and safety in protecting the nervous system. Advancements in isolation and characterization techniques, along with improved access to pure analytical standards, will play a critical role in achieving standardized, high-quality dietary supplements based on H. erinaceus. The aim of this study is to analyze the protective and nourishing effects of H. erinaceus on the nervous system and present the most up-to-date research findings related to this topic.

Four compounds, hericerin (1), isohericerinol A (2), N-de-phenylethyl isohericerin (3) and corallocin A (4) were isolated from the fruiting bodies of Hericium erinaceus, a lion's mane mushroom (Hericiaceae). Among them, isohericerinol A (2) was newly reported in nature. Further investigation of the neurotrophic effect of isolated compounds demonstrated that isohericerinol A (2) strongly increased the nerve growth factor (NGF) production in C6 glioma cells followed by corallocin A (4) and hericerin (1). Increased NGF production by these compounds promoted the neurite outgrowth in N2a neuronal cells. Western blot analysis also showed the increased protein expression of NGF, brain-derived neurotrophic factor (BDNF) and synaptophysin (SYP) in C6-N2a cells. Taken together, our present study characterized the neurotrophic constituents of H. erinaceus, which may support the potential use of memory improvement.

Depression is a common and severe neuropsychiatric disorder that is one of the leading causes of global disease burden. Although various anti-depressants are currently available, their efficacies are barely adequate and many have side effects. Hericium erinaceus, also known as Lion's mane mushroom, has been shown to have various health benefits, including antioxidative, antidiabetic, anticancer, anti-inflammatory, antimicrobial, antihyperglycemic, and hypolipidemic effects. It has been used to treat cognitive impairment, Parkinson's disease, and Alzheimer's disease. Bioactive compounds extracted from the mycelia and fruiting bodies of H. erinaceus have been found to promote the expression of neurotrophic factors that are associated with cell proliferation such as nerve growth factors. Although antidepressant effects of H. erinaceus have not been validated and compared to the conventional antidepressants, based on the neurotrophic and neurogenic pathophysiology of depression, H. erinaceus may be a potential alternative medicine for the treatment of depression. This article critically reviews the current literature on the potential benefits of H. erinaceus as a treatment for depressive disorder as well as its mechanisms underlying the antidepressant-like activities.

Basidiomycetes of the genus Hericium are among the most praised medicinal and edible mushrooms, which are known to produce secondary metabolites with the potential to treat neurodegenerative diseases. This activity has been attributed to the discovery of various terpenoids that can stimulate the production of nerve growth factor (NGF) or (as established more recently) brain-derived neurotrophic factor (BDNF) in cell-based bioassays. The present study reports on the metabolite profiles of a Lion's Mane mushroom (Hericium erinaceus) strain and a strain of the rare species, Hericium flagellum (synonym H. alpestre). While we observed highly similar metabolite profiles between the two strains that were examined, we isolated two previously undescribed metabolites, given the trivial names erinacines Z1 and Z2. Their chemical structures were elucidated by means of nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry. Along with six further, previously identified cyathane diterpenes, the novel erinacines were tested for neurotrophin inducing effects. We found that erinacines act on BDNF, which is a neurotrophic factor that has been reported recently by us to be induced by the corallocins, but as well on NGF expression, which is consistent with the literature.

Hericium erinaceus is well known for the neurotrophic effect it confers by promoting nerve growth factor biosynthesis. We discovered a novel bioactivity of H. erinaceus in its ability to suppress adenosine triphosphate (ATP)-induced calcium signaling in neuronal PC12 cells. ATP, known primarily as a neurotransmitter, also acts on purinoceptors (P2 purinergic receptor [P2R]) to generate the cellular calcium signaling and secretion that mediate P2R physiological manifestations, including pain. Chronic pain reduces quality of life. However, constant analgesic administration can cause liver and kidney injury, as well as loss of the analgesic effect because of desensitization. In this study we investigated the analgesic potential of H. erinaceus through measurements of ATP-induced Ca2+ signaling in cell lines and observation of pain behaviors in mice. In P2R-coupled Ca2+ signaling measurements, extracts of H. erinaceus mycelia (HEEs) blocked ATP-induced Ca2+ signaling in both rat PC12 cells and human HOS cells. HEEs completely blocked ATP-induced Ca2+ signaling in human HOS cells, suggesting that this effect of HEEs is exerted through the P2R subtypes present in HOS cells, which include the P2X4, P2X7, P2Y2, and P2Y4 subtypes. In observations of animal behavior during pain, HEEs significantly reduced heat-induced pain, including postponing both the tail-flick response to heat stimulation and the paw-lifting response to a hot plate. This study demonstrates novel characteristics of H. erinaceus in reducing nociceptive behavior and blocking the functional activity of P2R. Further studies are required to verify this linkage and its molecular mechanisms.

Neurotrophic factors are important in promoting the growth and differentiation of neurons. Nerve growth factor (NGF) is essential for the maintenance of the basal forebrain cholinergic system. Hericenones and erinacines isolated from the medicinal mushroom Hericium erinaceus can induce NGF synthesis in nerve cells. In this study, we evaluated the synergistic interaction between H. erinaceus aqueous extract and exogenous NGF on the neurite outgrowth stimulation of neuroblastoma-glioma cell NG108-15. The neuroprotective effect of the mushroom extract toward oxidative stress was also studied. Aqueous extract of H. erinaceus was shown to be non-cytotoxic to human lung fibroblast MRC-5 and NG108-15 cells. The combination of 10 ng/mL NGF with 1 μg/mL mushroom extract yielded the highest percentage increase of 60.6% neurite outgrowth. The extract contained neuroactive compounds that induced the secretion of extracellular NGF in NG108-15 cells, thereby promoting neurite outgrowth activity. However, the H. erinaceus extract failed to protect NG108-15 cells subjected to oxidative stress when applied in pre-treatment and co-treatment modes. In conclusion, the aqueous extract of H. erinaceus contained neuroactive compounds which induced NGF-synthesis and promoted neurite outgrowth in NG108-15 cells. The extract also enhanced the neurite outgrowth stimulation activity of NGF when applied in combination. The aqueous preparation of H. erinaceus had neurotrophic but not neuroprotective activities.

We present a model case study of the activity of aqueous extract of Hericium erinaceus fresh fruit bodies in promoting functional recovery following crush injury to the peroneal nerve in adult female Sprague-Dawley rats. The aim was to explore the possible use of this mushroom in nerve repair. The activities of aqueous extract were compared to activities exhibited by mecobalamin (vitamin B12), which has been widely used in the treatment of peripheral nerve disorders. Analysis of walking track indicated that return of hind limb function and normal toe spreading occurred earlier in treated groups than in the negative control (non-treated) group. Regeneration of axons and reinnervation of motor endplates/neuromuscular junction in extensor digitorum longus muscle of rats in treated groups developed better than in the negative control group. Further, immunofluorescence studies also showed that dorsal root ganglia neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt and MAPK signaling pathways as well as c-Jun and c-Fos genes compared to the negative control group. Akt cascade plays a major role in mediating neurotrophin-promoted cell survival, while MAPK cascade is involved in mediating neurite outgrowth. Immediate early gene expression was also involved in the cascade of events leading to regeneration. Local axonal protein synthetic machinery was also enhanced in the distal segments of crushed nerves in treated groups. Therefore, daily oral administration of H. erinaceus could promote the regeneration of injured rat peroneal nerve in the early stage of recovery.