Erinaceus Mycelium Research Articles

The Cerebral Protective Effect of Novel Erinacines from Hericium erinaceus Mycelium on In Vivo Mild Traumatic Brain Injury Animal Model and Primary Mixed Glial Cells via Nrf2-Dependent Pathways.

Hericium erinaceus, a consumable mushroom, has shown a potential to enhance the production of neuroprotective bioactive metabolites. Traumatic brain injury (TBI) often leads to cognitive, physical, and psychosocial impairments, resulting in neuroinflammation and the loss of cortical neurons. In this research, the effects of H. erinaceus mycelium, its derivative erinacine C, along with the underlying mechanisms, were examined in terms of oxidative stress modulation and neurological improvement in a rat model of mild traumatic brain injury (mTBI). Male Sprague-Dawley rats were administered diets containing H. erinaceus mycelium and erinacine C following experimental brain injury; these supplements were continued throughout the recovery phase. The binding activity of NF-E2-related factor 2 (Nrf2) near antioxidant genes in mixed glial cells was measured by chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). The motor beam walking test revealed that dietary supplementation of H. erinaceus mycelium resulted in modest improvements in spatial memory while inhibiting neuron cell death and microglial activation according to brain histological examination. These findings were further corroborated by the upregulation of several antioxidant enzymes (catalase, glutathione reductase, thioredoxin reductase, and superoxide dismutase) and phospho-CAMP-response element-binding (p-CREB) levels in the mTBI model treated with H. erinaceus mycelium. Erinacine C treatment led to significantly reduced brain inflammation and normalization of mTBI-induced deficits through the modulation of the Nrf2 activation pathway and upregulated expression of numerous Nrf2-binding antioxidant genes such as catalase, thioredoxin reductase, superoxide dismutase, and brain-derived neurotrophic factor. This study demonstrates the potential of H. erinaceus mycelium and erinacine C in facilitating recovery following mTBI, including the prevention of neuronal injury and inactivation of microglia through the Nrf2-mediated antioxidant pathway in vivo.

Erinacine S, a small active component derived from Hericium erinaceus, protects oligodendrocytes and alleviates mood abnormalities in cuprizone-exposed rodents

Hericium erinaceus mycelium extract (HEM), containing erinacine A (HeA) and erinacine S (HeS), has shown promise in promoting the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs), crucial for myelin production in the central nervous system (CNS). The main aim of this study was to characterize the protective effects of HEM and its components on OLs and myelin in demyelinating rodents by exposure to cuprizone (CPZ), a copper chelating agent commonly used to induce demyelination in the corpus callosum of the brain. Rats were fed by CPZ-containing diet and simultaneously orally administered HEM, HeA, or HeS on a daily basis for three weeks. We found that HEM and HeS preserved myelin and OLs in the corpus callosum of CPZ-fed rats, along with reduced microglia and astrocyte activation, and downregulated IL-1β expression. Furthermore, post-treatment with HeS, in mouse models with acute (6 weeks) or chronic (12 weeks) CPZ-induced demyelination demonstrated oral administration during the final 4 weeks (HeS4/6 or HeS4/12) effectively preserved myelin in the corpus callosum. Additionally, HeS4/6 and HeS4/12 inhibited anxious and depressive-like behaviors in CPZ-fed mice. In summary, simultaneous administration of HEM and HeS in rats during short-term CPZ intoxication preserved OLs and myelin. Furthermore, post-administration of HeS not only inhibited demyelination and gliosis but also alleviated anxiety and depression in both acute and chronic CPZ-fed mice. This study presents compelling evidence supporting the potential of HeS as a promising small active compound for protecting OLs and preserving myelin in demyelinating diseases associated with emotional disorders.

Benefits of Erinacines from Different Cultivate Formulas on Cognitive Deficits and Anxiety-Like Behaviour in Mice with Trimethyltin-Induced Toxicity.

We investigated the neurological effects of the varied erinacine composition of different mycelia cultures in mice with trimethyltin (TMT)-induced neurodegeneration. Forty male ICR mice were randomly divided into five groups of Sham-veh, TMT-veh, TMT-EME, TMT-EMR and TMT-EME/R. The TMT groups received 2.6 mg/kg one-time intraperitoneal injections of TMT. Oral dosages of 200 mg/kg erinacine combination from each Hericium erinaceus mycelia (EM) cultivated formula (100% eucalyptus wood [E], 100% rubber wood [R], or 40% eucalyptus wood/60% rubber wood [E/R]) were given for two weeks. Spatial learning, memory, flexibility, and anxious behaviour were evaluated alongside brain tissues' oxidative status and histological analyses. Erinacine composition from EME/R exhibited significant positive effects on spatial learning, memory, flexibility, and anxiety (p < 0.05). These findings emerged concurrently with the significant mitigation of hippocampal lipid peroxidation, CA1 hippocampal, cortical neuron, and corpus callosum white matter degeneration (p < 0.05). These neurological benefits were associated with the EME/R composition of erinacine A, C, D, G, H, I, K and R. The best neuroprotective effect against TMT-induced neurodegeneration in mice is offered by the EME/R erinacine composition according to its anti-lipid peroxidation, its nurturing effect on neuronal and white matter, and mitigation of behavioural deficits.

Erinacine S from Hericium erinaceus mycelium promotes neuronal regeneration by inducing neurosteroids accumulation.

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. Using RNA-seq and bioinformatic analyses, erinacine S was found to cause the accumulation of neurosteroids in neurons. ELISA and neurosteroidogenesis inhibitor assays were performed to validate this effect. This research uncovers a previously unknown effect of erinacine S on raising the level of neurosteroids.

The protective effect of erinacine A–enriched Hericium erinaceus mycelium ethanol extract on oxidative Stress–Induced neurotoxicity in cell and Drosophila models of spinocerebellar ataxia type 3

The protective effect of erinacine A–enriched Hericium erinaceus mycelium ethanol extract on oxidative Stress–Induced neurotoxicity in cell and Drosophila models of spinocerebellar ataxia type 3

Hericium erinaceus Mycelium Ameliorates In Vivo Progression of Osteoarthritis.

Osteoarthritis (OA) is an age-related disorder that affects the joints and causes functional disability. Hericium erinaceus is a large edible mushroom with several known medicinal functions. However, the therapeutic effects of H. erinaceus in OA are unknown. In this study, data from Sprague-Dawley rats with knee OA induced by anterior cruciate ligament transection (ACLT) indicated that H. erinaceus mycelium improves ACLT-induced weight-bearing asymmetry and minimizes pain. ACLT-induced increases in articular cartilage degradation and bone erosion were significantly reduced by treatment with H. erinaceus mycelium. In addition, H. erinaceus mycelium reduced the synthesis of proinflammatory cytokines interleukin-1β and tumor necrosis factor-α in OA cartilage and synovium. H. erinaceus mycelium shows promise as a functional food in the treatment of OA.

Natural Compound 2-Chloro-1,3-dimethoxy-5-methylbenzene, Isolated from Hericium Erinaceus, Inhibits Fungal Growth by Disrupting Membranes and Triggering Apoptosis.

In this study, 2-chloro-1,3-dimethoxy-5-methylbenzene (CDM), a natural product with anti-Candida albicans activity, was discovered from the Hericium erinaceus mycelium. The minimum inhibitory concentration of CDM was 62.5 μg/mL. Moreover, structural analogues of CDM obtained from chemical synthesis were applied to explore the structure-activity relationship (SAR) of CDM against C. albicans. It was found that methoxy groups, halogen atoms (except fluorine atoms), and methoxy-meta-position methyl groups in the structure of CDM were the key active groups. Furthermore, we investigated the anti-C. albicans mechanism of CDM. Experiments suggested that CDM destroyed the cell membrane of C. albicans, including the cytoplasmic membrane and mitochondrial membrane, and caused the accumulation of reactive oxygen species and mitochondrial dysfunction, which ultimately led to apoptosis of C. albicans. In addition, CDM had no toxicity on human normal gastric mucosal epithelial cells exposed to a concentration of 125 μg/mL. Experiments showed that CDM reduced the damage of C. albicans to the visceral tissue of infected mice and improved the survival rate of mice. Our research provides a scientific basis for the discovery of effective and safe anti-C. albicans drugs from H. erinaceus.

Identification of Common Liver Metabolites of the Natural Bioactive Compound Erinacine A, Purified from Hericium erinaceus Mycelium

Metabolite identification, in the early stage, for compound discovery is necessary to assess the knowledge for the pharmaceutical improvement of drug safety and efficacy. Even if the drug has been released into the market, identification and continuous evaluation of the metabolites are required to avoid the risk of post-marketing withdrawal. Hericium erinaceus (HE), a medicinal mushroom, has broadly documented nutraceutical benefits, including anti-oxidant, anti-tumor, anti-aging, hypolipidemic, and gastric mucosal protection effects. Recently, erinacine A has been reported as the main natural bioactive compound in the mycelium of HE for functional food development. In neurological studies, the consumption of enrinacine A enriched HE mycelium demonstrates its significant nutraceutical effects in Alzheimer’s disease, Parkinson’s disease, and ischemic stroke. For the first time, we explored the metabolic process of erinacine A molecule and identified its metabolites from the rat and human liver S9 fraction. Using a liquid chromatography/triple quadrupole mass spectrometer for quantitative analysis, we observed that 75.44% of erinacine A was metabolized within 60 min in rat, and 32.34% of erinacine A was metabolized within 120 min in human S9. Using an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) to identify the metabolites of erinacine A, five common metabolites were identified, and their possible structures were evaluated. Understanding the metabolic process of erinacine A and establishing its metabolite profile database will help promote the nutraceutical application and discovery of related biomarkers in the future.

Comparison of Protective Effects of Hericium erinaceus Extracts Prepared by Different Methods on Acute Gastric Mucosal Injury in Rats

Using absolute ethanol as an inducer, a rat model of acute gastric mucosal injury was constructed, and the protective effects of Hericium erinaceus crude extract prepared in several different ways on the model of acute gastric mucosal injury induced by absolute ethanol were studied. Female SD rats were randomly divided into 7 groups (n=12): Normal control group (NC), model control group (ETH), Hericium erinaceus fruit body polysaccharide intervention group(WEH1), Hericium erinaceus mycelium polysaccharide intervention group (WEH2), Hericium erinaceus water extract intervention group (WEH3), liquid fermentation water extract intervention group (WEH4) and bismuth potassium citrate granule drug group (YWZ). In each sample groups, the gavage dose (10 mL/kg) of the sample was adjusted according to the weight change, and the sample was given 167 mg/kg, bismuth potassium citrate granules (0.24 g/kg, containing 24.1 mg of bismuth) for continuous intragastric administration for 30 days. Then the normal control group and the model group were directly given distilled water, and 5 mL/kg of absolute ethanol was used to make the model. By comparing the degree of injury of gastric mucosal tissue slices, the level of inflammatory factors and the antioxidant capacity. Finally the results showed that comparing with the model group, the experimental group had significantly reduced gastric mucosal bleeding, congestion, necrosis, and pathology, and the total pathological scores were significantly different (P<0.05), the activities of superoxide dismutase (SOD) and glutathione (GSH) were significantly increased (P<0.05), the content of malondialdehyde (MDA), tumor necrosis factor-α in serum and gastric tissue (TNF-α), interleukin-6(IL-6), interleukin-1β (IL-1β) inflammatory factors levels were significantly reduced (P<0.05). So the tests have shown that several Hericium erinaceus extracts have varying degrees of protection against gastric mucosal damage in rats induced by absolute ethanol, among of them, the Hericium erinaceus mycelium polysaccharide has the best protective effect, while its mechanism of action may be similar to that of anti- oxidation is related to anti-inflammatory effects. The research results could provide a research foundation for the development and promotion of functional products of different Hericium erinaceus extracts.

Erinacine A Prevents Lipopolysaccharide-Mediated Glial Cell Activation to Protect Dopaminergic Neurons against Inflammatory Factor-Induced Cell Death In Vitro and In Vivo.

Hericium erinaceus (HE) is a common edible mushroom consumed in several Asian countries and considered to be a medicinal mushroom with neuroprotective effects. Erinacine A (EA) is a bioactive compound in Hericium erinaceus mycelium (HEM) that has been shown to have a neuroprotective effect against neurodegenerative diseases, e.g., Parkinson’s disease (PD). Although the etiology of PD is still unclear, neuroinflammation may play an important role in causing dopaminergic neuron loss, which is a pathological hallmark of PD. However, glial cell activation has a close relationship with neuroinflammation. Thus, this study aimed to investigate the anti-neuroinflammatory and neuroprotective effects of EA on lipopolysaccharide (LPS)-induced glial cell activation and neural damage in vitro and in vivo. For the in vitro experiments, glial cells, BV-2 microglial cells and CTX TNA2 astrocytes were pretreated with EA and then stimulated with LPS and/or IFN-γ. The expression of proinflammatory factors in the cells and culture medium was analyzed. In addition, differentiated neuro-2a (N2a) cells were pretreated with EA or HEM and then stimulated with LPS-treated BV-2 conditioned medium (CM). The cell viability and the amount of tyrosine hydroxylase (TH) and mitogen-activated protein kinases (MAPKs) were analyzed. In vivo, rats were given EA or HEM by oral gavage prior to injection of LPS into the substantia nigra (SN). Motor coordination of the rats and the expression of proinflammatory mediators in the midbrain were analyzed. EA pretreatment prevented LPS-induced iNOS expression and NO production in BV-2 cells and TNF-α expression in CTX TNA2 cells. In addition, both EA and HEM pretreatment significantly increased cell viability and TH expression and suppressed the phosphorylation of JNK and NF- κB in differentiated N2a cells treated with CM. In vivo, both EA and HEM significantly improved motor dysfunction in the rotarod test and the amphetamine-induced rotation test and reduced the expression of TNF-α, IL-1β and iNOS in the midbrain of rats intranigrally injected with LPS. The results demonstrate that EA ameliorates LPS-induced neuroinflammation and has neuroprotective properties.

Biological activities and chemical profile of Hericium erinaceus mycelium cultivated on mixed red and white jasmine rice

Functional foods have received considerable attention due to their numerous health benefits. Lion's mane mushroom (Hericium erinaceus) is a functional food source that contains bioactive compounds of medicinal importance. The main aim of this study was to explore antimicrobial and anticancer activities and identify bioactive compounds of H. erinaceus mycelia cultivated on mixed red and white jasmine rice (HMR) with the aid of solid-state fermentation (SSF). The HMR extract and its fractions were analyzed for antibacterial activity via disc diffusion and minimum inhibitory concentration (MIC) assays and anticancer activity against cervical cancer (HeLa) examined with the [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] (MTS) assay. Chemical profiles were analyzed using gas chromatography-mass spectrometry (GC-MS). Our results showed that the lipophilic fraction (LF2) had antibacterial activity against P. mirabilis (MIC = 250 µg/mL). LF2 is primarily composed of fatty acid derivatives with antibacterial components, including nonanoic acid, 2-dodecen-1-yl(-) succinic anhydride, linoleic acid ethyl ester, 3,4-dimethylbenzoic acid, and lauryl acetate. However, all HMR fractions displayed relatively weak anticancer activity (IC50 > 100 µg/mL). Our collective findings support the potential utility of H. erinaceus mycelium cultivated on mixed red and white jasmine rice as an antibacterial agent.

Hericium erinaceus mycelium ameliorate anxiety induced by continuous sleep disturbance in vivo

BackgroundSleep disruption is a major public health issue and may increase the risk of mortality by ten-folds if an individual is sleeping less than 6 h per night. Sleep has changed dramatically during to the COVID-19 pandemic because COVID symptoms can lead to psychological distress including anxiety. Hericium erinaceus mycelium has been widely investigated in both the in vivo studies and clinical trials for its neuroprotective functions because the mycelium contains hericenones and erinacines, which synthesize the nerve growth factor and brain-derived neurotrophic factor (BDNF). Recent in vivo reports have shown showed that erinacine A-enriched Hericium erinaceus mycelium can modulate BDNF/TrkB/PI3K/Akt/GSK-3β pathways to induce an antidepressant-like effect. A large body of evidence indicates that erinacine can pass the blood-brain barrier and suggests its neuroprotective function in both peripheral and central nervous systems. Thus, Hericium erinaceus mycelium may be a dual-function supplement for sleep disruption improvement while sustaining anxiolytic effects.MethodTo simulate the condition of sleep disruption, the mice were subjected to the tail suspension test (TST) for 15 min every day during the same period for nine consecutive days. Two different doses (75 and 150 mg/kg) of Hericium erinaceus mycelium were administered orally 20 min prior to the TSTs before entering the light period of 12:12 h L:D cycle. All sleep-wake recording was recorded for 24 h using electroencephalogram and electromyogram. The elevated-plus-maze and open-field tests were conducted to record the behavior activities.ResultsConsecutive TSTs prior to the light period could cause significant sleep disturbance and anxiety behavior in the elevated-plus-maze experiments. Results showed that administration with Hericium erinaceus mycelium at 150 mg/kg ameliorated the rodent anxiety (p < 0.05) and reversed the TST-induced NREM sleep disturbance in the dark period.ConclusionThis is the first in vivo study suggesting that Hericium erinaceus mycelium has a dual potential role for anxiety relief through improving sleep disruptions.

Study on the interaction of Hericium erinaceus mycelium polysaccharides and its degradation products with food additive silica nanoparticles

Gastric mucosal injury is a common gastrointestinal disorder. Hericium erinaceus polysaccharide, the major active ingredient in Hericium erinaceus, can reduce gastric mucosal damage to some extent. In this study, two different products HMP-Vc and HMP-Ce were obtained by Vitamin C and cellulase degradation of Hericium erinaceus mycelium polysaccharide (HMP). The gastroprotective activity of polysaccharides and its interaction products with food additives silica nanoparticles (nSiO2) were studied in GES-1 cells. It was found that gastroprotective activity of HMP was significantly higher than that of degradation products, and the addition of nSiO2 could enhance this activity of HMP. The greatest difference between the degradation products and HMP was the reduction of the triple helix structure, which might be the reason of the gastroprotective activity was less than that of HMP. Moreover, nSiO2 might interact with HMP through hydrogen bonding to enhance its activity.

Erinacine A-Enriched Hericium erinaceus Mycelium Delays Progression of Age-Related Cognitive Decline in Senescence Accelerated Mouse Prone 8 (SAMP8) Mice.

There have been many reports on the neuroprotective effects of Hericium erinaceus mycelium, in which the most well-known active compounds found are diterpenoids, such as erinacine A. Previously, erinacine A-enriched Hericeum erinaceus mycelium (EAHEM) was shown to decrease amyloid plaque aggregation and improve cognitive disability in Alzheimer’s disease model APP/PS1 mice. However, its effects on brain aging have not yet been touched upon. Here, we used senescence accelerated mouse prone 8 (SAMP8) mice as a model to elucidate the mechanism by which EAHEM delays the aging of the brain. Three-month-old SAMP8 mice were divided into three EAHEM dosage groups, administered at 108, 215 and 431 mg/kg/BW/day, respectively. During the 12th week of EAHEM feeding, learning and memory of the mice were evaluated by single-trial passive avoidance and active avoidance test. After sacrifice, the amyloid plaques, induced nitric oxidase synthase (iNOS) activity, thiobarbituric acid-reactive substances (TBARS) and 8-OHdG levels were analyzed. We found that the lowest dose of 108 mg/kg/BW EAHEM was sufficient to significantly improve learning and memory in the passive and active avoidance tests. In all three EAHEM dose groups, iNOS, TBARS and 8-OHdG levels all decreased significantly and showed a dose-dependent response. The results indicate that EAHEM improved learning and memory and delayed degenerative aging in mice brains.

Antioxidant and anti-Helicobacter pylori activities of Hericium erinaceus mycelium and culture filtrate

Introduction: Hericium erinaceus is known as a medicinal edible mushroom owing to its antimicrobial, antioxidant, anti-tumor and immunomodulatory effects. Helicobacter pylori infection is one of the major health concerns worldwide due to its high rate in global populations, frequent recurrence, and rapid emergence of drug-resistant strains. The present study aims to investigate antioxidant anti-H. pylori and urease inhibitory activities of solvent fractions from H. erinaceus mycelium and culture filtrate.&#x0D; Methods: H. erinaceus mycelium was purely cultured in a liquid medium. A polysaccharide fraction was obtained from the culture filtrate by precipitation with ethanol. The mycelium and culture filtrate were extracted by liquid extraction to obtain solvent-soluble fractions. The antibacterial effects of these fractions were determined using paper disc diffusion and broth microdilution assays. Urease inhibition was determined using the salicylate-hypochlorite method. The antioxidant activity of H. erinaceus was evaluated via 2,2,1-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity.&#x0D; Results: The ethyl-acetate (EtOAc) fractions derived from H. erinaceus culture filtrate (fEtOAc Fr.) and mycelium (mEtOAc Fr.) showed the strongest anti-H. pylori activity with MIC (MBC) of 1.25 – 1.5 (5.0 – 7.5) mg/mL and potential urease inhibitory activity with IC50 of 0.34 – 0.35 mg/mL. In addition, fEtOAc Fr. exhibited the greatest antioxidant activity (IC50, 11.83 mg/mL), which was slightly stronger than that of mEtOAc Fr. (IC50, 14.75 mg/mL). Moreover, our study also found that the water fractions from the culture filtrate (fWater Fr.) and the mycelium (mWater Fr.) displayed considerable inhibitory activities against bacterial urease (IC50, 1.26 – 1.40 mg/mL), although they had low or no anti-H. pylori activities and low antioxidant properties.&#x0D; Conclusion: The present study revealed that the EtOAC fractions derived from the H. erinaceus mycelium and culture filtrate potentially have anti-H. pylori, anti-urease and antioxidant activities. These results suggest that H. erinaceus mycelium and culture filtrate could be utilized to develop functional foods and nutraceuticals to prevent H. pylori infection. More research is needed to prove the safety of the H. erinaceus mycelium and culture filtrate fractions and their in vivo efficacy in the treatment of H. pylori infection.

Hericium erinaceus mycelium and its small bioactive compounds promote oligodendrocyte maturation with an increase in myelin basic protein

Oligodendrocytes (OLs), myelin-producing glia in the central nervous system (CNS), produce a myelin extension that enwraps axons to facilitate action potential propagation. An effective approach to induce oligodendrogenesis and myelination is important to foster CNS development and promote myelin repair in neurological diseases. Hericium (H.) erinaceus, an edible and culinary-medicinal mushroom, has been characterized as having neuroprotective activities. However, its effect on OL differentiation has not yet been uncovered. In this study using oligodendrocyte precursor cell (OPC) cultures and an ex vivo cerebellar slice system, we found that the extract from H. erinaceus mycelium (HEM) not only promoted the differentiation of OPCs to OLs in the differentiation medium, but also increased the level of myelin basic protein (MBP) on neuronal fibers. Moreover, daily oral administration of HEM into neonatal rat pups for 7 days enhanced MBP expression and OLs in the corpus callosum of the postnatal rat brain. The effect of HEM-derived bioactive compounds, the diterpenoid xylosides erinacine A (HeA) and HeC and a sesterterpene with 5 isoprene units called HeS, were further evaluated. The results showed that HeA and HeS more potently stimulated MBP expression in OLs and increased the number of OLs. Moreover, overlap between MBP immunoreactivity and neuronal fibers in cultured cerebellar tissue slices was significantly increased in the presence of HeA and HeS. In summary, our findings indicate that HEM extract and its ingredients HeA and HeS display promising functional effects and promote OL maturation, providing insights into their potential for myelination in neurodevelopmental disorders.

Retraction Note to: Hericium erinaceus mycelium and its isolated erinacine A protection from MPTP-induced neurotoxicity through the ER stress, triggering an apoptosis cascade

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12967-016-0831-y.

Prevention of Early Alzheimer's Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study.

ObjectiveTo investigate the efficacy and safety of three H. erinaceus mycelia (EAHE) capsules (350 mg/capsule; containing 5 mg/g erinacine A active ingredient) per day for the treatment of patients with mild Alzheimer’s Disease (AD).MethodsThis study comprised a 3-week no-drug screening period, followed by a 49-week double-blind treatment period with 2-parallel groups in which eligible patients were randomized to either three 5 mg/g EAHE mycelia capsules per day or identical appearing placebo capsules. Cognitive assessments, ophthalmic examinations, biomarker collection, and neuroimaging were followed throughout the study period.ResultsAfter 49 weeks of EAHE intervention, a significant decrease in Cognitive Abilities Screening Instrument score was noted in the placebo group, a significant improvement in Mini-Mental State Examination score was observed in the EAHE group and a significant Instrumental Activities of Daily Living score difference were found between the two groups. In addition, EAHE group achieved a significantly better contrast sensitivity when compared to the placebo group. Moreover, only the placebo group observed significantly lowered biomarkers such as calcium, albumin, apolipoprotein E4, hemoglobin, and brain-derived neurotrophic factor and significantly elevated alpha1-antichymotrypsin and amyloid-beta peptide 1–40 over the study period. Using diffusion tensor imaging, the mean apparent diffusion coefficient (ADC) values from the arcuate fasciculus region in the dominant hemisphere significantly increased in the placebo group while no significant difference was found in the EAHE group in comparison to their baselines. Moreover, ADC values from the parahippocampal cingulum region in the dominant hemisphere significantly decreased in the EAHE group whereas no significant difference was found in the placebo group when compared to their baselines. Lastly, except for four subjects who dropped out of the study due to abdominal discomfort, nausea, and skin rash, no other adverse events were reported.ConclusionThree 350 mg/g EAHE capsules intervention for 49 weeks demonstrated higher CASI, MMSE, and IADL scores and achieved a better contrast sensitivity in patients with mild AD when compared to the placebo group, suggesting that EAHE is safe, well-tolerated, and may be important in achieving neurocognitive benefits.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT04065061.

Post-Treatment with Erinacine A, a Derived Diterpenoid of H. erinaceus, Attenuates Neurotoxicity in MPTP Model of Parkinson's Disease.

Hericium erinaceus, a valuable pharmaceutical and edible mushroom, contains potent bioactive compounds such as H. erinaceus mycelium (HEM) and its derived ethanol extraction of erinacine A, which have been found to regulate physiological functions in our previous study. However, HEM or erinacine A with post-treatment regimens also shows effects on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity, but its mechanisms remain unknown. By using annexin-V–fluorescein-isothiocyanate (FITC)/propidium iodide staining and a 2’,7’ –dichlorofluorescin diacetate (DCFDA) staining assay, the cell death, cell viability, and reactive oxygen species (ROS) of 1-methyl-4-phenylpyridinium (MMP+)-treated Neuro-2a (N2a) cells with or without erinacine A addition were measured, respectively. Furthermore, signaling molecules for regulating the p21/GADD45 cell death pathways and PAKalpha, p21 (RAC1) activated kinase 1 (PAK1) survival pathways were also detected in the cells treated with MPP+ and erinacine A by Western blots. In neurotoxic animal models of MPTP induction, the effects of HEM or erinacine A and its mechanism in vivo were determined by measuring the TH-positive cell numbers and the protein level of the substantia nigra through a brain histological examination. Our results demonstrated that post-treatment with erinacine A was capable of preventing the cytotoxicity of neuronal cells and the production of ROS in vitro and in vivo through the neuroprotective mechanism for erinacine A to rescue the neurotoxicity through the disruption of the IRE1α/TRAF2 interaction and the reduction of p21 and GADD45 expression. In addition, erinacine A treatment activated the conserved signaling pathways for neuronal survival via the phosphorylation of PAK1, AKT, LIM domain kinase 2 (LIMK2), extracellular signal-regulated kinases (ERK), and Cofilin. Similar changes in the signal molecules also were found in the substantia nigra of the MPTP, which caused TH+ neuron damage after being treated with erinacine A in the post-treatment regimens in a dose-dependent manner. Taken together, our data indicated a novel mechanism for post-treatment with erinacine A to protect from neurotoxicity through regulating neuronal survival and cell death pathways.

Effects of Hericium erinaceus Mycelium Extracts on the Functional Activity of Purinoceptors and Neuropathic Pain in Mice with L5 Spinal Nerve Ligation.

Neuropathic pain is a serious clinical problem that is difficult to treat. Purinoceptors (P2Rs) transduce pain perception from the peripheral to the central nervous system and play an important role in the transmission of neuropathic pain signals. We previously found that the crude extracts of Hericium erinaceus mycelium (HE-CE) inhibited P2R-mediated signaling in cells and reduced heat-induced pain in mice. The present study explored the effects of HE-CE on neuropathic pain. We used adenosine triphosphate (ATP) as a P2R agonist to generate Ca2+ signaling and neuronal damage in a cell line. We also established a neuropathic mouse model of L5 spinal nerve ligation (L5-SNL) to examine neuropathic pain and neuroinflammation. Neuropathic pain was recorded using the von Frey test. Neuroinflammation was evaluated based on immunohistofluorescence observation of glial fibrillary acidic protein (GFAP) levels in astrocytes, ionized calcium-binding adaptor molecule1 (iba1) levels in microglia, and IL-6 levels in plasma. The results show that HE-CE and erinacine-S, but not erinacine-A, totally counteracted Ca2+ signaling and cytotoxic effects upon P2R stimulation by ATP in human osteosarcoma HOS cells and human neuroblastoma SH-SY5Y cells, respectively. SNL induced a decrease in the withdrawal pressure of the ipsilateral hind paw, indicating neuropathic pain. It also raised the GFAP level in astrocytes, the iba1 level in microglia, and the IL-6 level in plasma, indicating neuroinflammation. HE-CE significantly counteracted the SNL-induced decrease in withdrawal pressure, illustrating that it could relieve neuropathic pain. It also reduced SNL-induced increases in astrocyte GFAP levels, microglial iba1 levels, and plasma IL-6 levels, suggesting that HE-CE reduces neuroinflammation. Erinacine-S relieved neuropathic pain better than HE-CE. The present study demonstrated that HE inhibits P2R and, thus, that it can relieve neuropathic pain and neuroinflammation.