Hericium Erinaceus Research Articles

Isolation and Purification of Fungal β-Glucan as an Immunotherapy Strategy for Glioblastoma.

One of the biggest challenges in developing effective therapies against glioblastoma is overcoming the strong immune suppression within the tumor microenvironment. Immunotherapy has emerged as an effective strategy to turn the immune system response against tumor cells. Glioma-associated macrophages and microglia (GAMs) are major drivers of such anti-inflammatory scenarios. Therefore, enhancing the anti-cancerous response in GAMs may represent a potential co-adjuvant therapy to treat glioblastoma patients. In that vein, fungal β-glucan molecules have long been known as potent immune modulators. Their ability to stimulate the innate immune activity and improve treatment response has been described. Those modulating features are partly attributed to their ability to bind to pattern recognition receptors, which, interestingly, are greatly expressed in GAMs. Thus, this work is focused on the isolation, purification, and subsequent use of fungal β-glucans to enhance the tumoricidal response of microglia against glioblastoma cells. The mouse glioblastoma (GL261) and microglia (BV-2) cell lines are used to test the immunomodulatory properties of four different fungal β-glucans extracted from mushrooms heavily used in the current biopharmaceutical industry: Pleurotus ostreatus, Pleurotus djamor, Hericium erinaceus,and Ganoderma lucidum. To test these compounds, co-stimulation assays were performed to measure the effect of a pre-activated microglia-conditioned medium on the proliferation and apoptosis activation in glioblastoma cells.

Structural characterization of Hericium erinaceus polysaccharides and the mechanism of anti-T2DM by modulating the gut microbiota and metabolites

A low molecular weight polysaccharides of HEP-1, with molecular weights of 1.67 × 104 Da and composition of →6)-β-D-Glcp-(1→, →3)-β-D-Glcp-(1→, β-D-Glcp-(1→ and →3,6)-β-D-Glcp-(1→, was isolated and characterized from the fruiting body of Hericium erinaceus. The results indicated that HEP-1 showed potential effects against T2DM-induced imbalance of glucose and lipid metabolism by promoting the serum glucose uptake by hepatic glycogen synthesis via activating the IRS/PI3K/AKT signaling pathway, and inhibiting fatty acid synthesis and reducing hepatic lipid accumulation via activating the AMPK/SREBP-1c signaling pathways. Besides, HEP-1 promoted the production of beneficial bacteria in the gut, and increased the beneficial metabolites in liver through the gut-liver axis, consequently, resisting the occurrence of T2DM.

Issue Information

Journal of NeurochemistryVolume 165, Issue 6 p. 757-758 ISSUE INFORMATIONFree Access Issue Information First published: 22 June 2023 https://doi.org/10.1111/jnc.15634 Read the full article: ‘Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory’ by R. Martínez-Mármol, Y. Chai, J. N. Conroy, Z. Khan, S.-M. Hong, S. B. Kim, R. S. Gormal, D. H. Lee, J. K. Lee, E. J. Coulson, M. K. Lee, S. Y. Kim, and F. A. Meunier (J. Neurochem. vol. 165 (6), pp. 791–808) on doi:10.1111/jnc.15767 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Graphical Abstract Front cover The traditional medicinal mushroom Hericium erinaceus, also known as lion’s mane mushroom has bioactive compounds with neurotrophic activity. Here, we purified and identified biologically active molecules isolated from H. erinaceus, based on their ability to promote neurite extensive outgrowth in hippocampal neurons. We found that N-de phenylethyl isohericerin (NDPIH) and its hydrophobic derivative hericene A, were highly potent in inducing neurite outgrowth and branching in cultured hippocampal neurons. In addition, mice feed with hericene A showed both increased BDNF signaling and enhanced hippocampal memory performance. Biochemical analysis revealed that the aforementioned neurotrophic effects are independent but convergent to BDNF/TrkB pathway. Our results reveal potent bioactive compounds derived from H. erinaceus. These molecules are very attractive compounds for their neurotrophic properties. Our findings open the door to identifying novel mushroom-derived compounds as an strategy for the development of sustainable therapeutical interventions to revert the cognitive decline associated with ageing and neurodegenerative diseases. Image content Confocal image of a giant growth cone from an hippocampal neuron elicited by NDPIH. Immunocytochemistry against tubulin (mouse anti-βIII tubulin primary antibody, and Alexa FluorTM 488-goat-anti-mouse secondary antibody, green) and actin (Alexa-FluorTM 647-phalloidin, magenta). Read the full article ‘Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory’ by R. Martínez-Mármol, Y. Chai, J. N. Conroy, Z. Khan, S.-M. Hong, S. B. Kim, R. S. Gormal, D. H. Lee, J. K. Lee, E. J. Coulson, M. K. Lee, S. Y. Kim, and F. A. Meunier (J. Neurochem. vol. 165 (6), pp. 791–808) on doi:10.1111/jnc.15767 Volume165, Issue6June 2023Pages 757-758 RelatedInformation

Hericium erinaceus, a medicinal fungus with a centuries-old history: Evidence in gastrointestinal diseases.

Hericium erinaceus is an edible and medicinal mushroom commonly used in traditional Chinese medicine for centuries. Several studies have highlighted its therapeutic potential for gastrointestinal disorders such as gastritis and inflammatory bowel diseases. In addition, some components of this mushroom appear to possess strong antineoplastic capabilities against gastric and colorectal cancer. This review aims to analyse all available evidence on the digestive therapeutic potential of this fungus as well as the possible underlying molecular mechanisms.

Physicochemical Characterization and Antimicrobial Analysis of Vegetal Chitosan Extracted from Distinct Forest Fungi Species.

The main goal of this investigation is to conduct a thorough analysis of the physical, chemical, and morphological characteristics of chitosan derived from various forest fungi. Additionally, the study aims to determine the effectiveness of this vegetal chitosan as an antimicrobial agent. In this study, Auricularia auricula-judae, Hericium erinaceus, Pleurotus ostreatus, Tremella fuciformis, and Lentinula edodes were examined. The fungi samples were subjected to a series of rigorous chemical extraction procedures, including demineralization, deproteinization, discoloration, and deacetylation. Subsequently, the chitosan samples were subjected to a comprehensive physicochemical characterization analysis, encompassing Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), degree of deacetylation determination, ash content determination, moisture content determination, and solubility determination. To evaluate the antimicrobial efficacy of the vegetal chitosan samples, two different sampling parameters were employed, namely human hand and banana, to assess their effectiveness in inhibiting microbial growth. Notably, the percentage of chitin and chitosan varied significantly among the distinct fungal species examined. Moreover, EDX spectroscopy confirmed the extraction of chitosan from H. erinaceus, L. edodes, P. ostreatus, and T. fuciformis. The FTIR spectra of all samples revealed a similar absorbance pattern, albeit with varying peak intensities. Furthermore, the XRD patterns for each sample were nearly identical, with the exception of the A. auricula-judae sample, which exhibited sharp peaks at ~37° and ~51°, while the crystallinity index of this same sample was approximately 17% lower than the others. The moisture content results indicated that the L. edodes sample was the least stable, while the P. ostreatus sample was the most stable, in terms of degradation rate. Similarly, the solubility of the samples showed substantial variation among each species, with the H. erinaceus sample displaying the highest solubility among the rest. Lastly, the antimicrobial activity of the chitosan solutions exhibited different efficacies in inhibiting microbial growth of skin microflora and microbes found on the peel of Musa acuminata × balbisiana.

Hericium erinaceus in Neurodegenerative Diseases: From Bench to Bedside and Beyond, How Far from the Shoreline?

A growing number of studies is focusing on the pharmacology and feasibility of bioactive compounds as a novel valuable approach to target a variety of human diseases related to neurological degeneration. Among the group of the so-called medicinal mushrooms (MMs), Hericium erinaceus has become one of the most promising candidates. In fact, some of the bioactive compounds extracted from H. erinaceus have been shown to recover, or at least ameliorate, a wide range of pathological brain conditions such as Alzheimer's disease, depression, Parkinson's disease, and spinal cord injury. In a large body of in vitro and in vivo preclinical studies on the central nervous system (CNS), the effects of erinacines have been correlated with a significant increase in the production of neurotrophic factors. Despite the promising outcome of preclinical investigations, only a limited number of clinical trials have been carried out so far in different neurological conditions. In this survey, we summarized the current state of knowledge on H. erinaceus dietary supplementation and its therapeutic potential in clinical settings. The bulk collected evidence underlies the urgent need to carry out further/wider clinical trials to prove the safety and efficacy of H. erinaceus supplementation, offering significant neuroprotective applications in brain pathologies.

Biocatalytic characterization of Hericium erinaceus laccase isoenzymes for the oxidation of lignin derivative substrates

Mushroom laccases are biocatalysts that oxidize various substrates. To identify a novel enzyme involved in lignin valorization, we isolated and characterized laccase isoenzymes from the mushroom Hericium erinaceus. The laccase cDNAs (Lac1a and Lac1b) cloned from the mushroom mycelia consisted of 1536 bp and each encoded a protein with 511 amino acids, containing a 21-amino-acid signal peptide. Comparative phylogenetic analysis revealed high homology between the deduced amino acid sequences of Lac1a and Lac1b and those from basidiomycetous fungi. In the Pichia pastoris expression system, high extracellular production of Lac1a, a glycoprotein, was achieved, whereas Lac1b was not expressed as a secreted protein because of hyper-glycosylation. Biochemical characterization of the purified recombinant Lac1a (rLac1a) protein revealed its oxidizing efficacy toward 14 aromatic substrates. The highly substrate-specific rLac1a showed catalytic efficiencies of 877 s−1 mM−1, 829 s−1 mM−1, 520 s−1 mM−1, and 467 s−1 mM−1 toward 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), hydroquinone, guaiacol, and 2,6-dimethylphenol, respectively. Moreover, rLac1a showed approximately 10 % higher activity in non-ionic detergents and >50 % higher residual activity in various organic solvents. These results indicate that rLac1a is a novel oxidase biocatalyst for the bioconversion of lignin into value-added products.

Screening of medicinal mushroom strains with antimicrobial activity and polysaccharides production

AbstractObjectivesThis study aimed to determine the antimicrobial activity of culture fluid and mycelial mass of selectedHericiumstrains from the IBK Mushroom Culture Collection (Kyiv, Ukraine) against bacteria and fungi, as well as to evaluate the potential of these mushrooms for biomass and extracellular polysaccharides production.MethodsThe antimicrobial activity of ethyl acetate extracts of culture fluid and aqueous-ethyl extracts of mycelial mass for threeHericiumspecies:Hericium cirrhatumIBK 2393,Hericium coralloidesIBK 2332, andHericium erinaceusIBK 2530 against Gram-positiveBacillus subtilis,Staphylococcus aureus, and Gram-negativeEscherichia coli,Klebsiella pneumoniae,Pseudomonas aureginosabacteria as well asAspergillus niger,Penicillium polonicum, andMucor globosusfungi by the disk diffusion method was conducted. Analysis of the minimum inhibitory concentration was carried out according to the broth dilution method.ResultsHigh antimicrobial activity of culture fluid extracts ofHericiummushroom species againstS. aureuswas established after 14–21 days of cultivation. No effects ofHericiumextracts againstA. niger,P. polonicum, andM. globosuswere observed. On the 7th day of submerged cultivation, the studied strains produced the maximum yield of extracellular polysaccharides. The most promising extracellular polysaccharide (EPS) producers were strains ofH. coralloidesIBK 2332 (1.89 g/L) andH. erinaceusIBK 2530 (1.90 g/L). The maximal value of biomass was produced byH. cirrhatumIBK 2393 on the 21st day of submerged cultivation (17.45 g/L).ConclusionsHericiummushrooms have significant potential for the development of new drugs with health benefits properties.

The effects of Hericium erinaceus extracts on cell viability and telomerase activity in MCF-7 cells

Abstract Objectives This study aims to determine the effects of Hericium erinaceus extracts on cell viability and the effects of H. erinaceus water extract on the telomerase activity of MCF-7 cells. H. erinaceus is an edible mushroom widely used in traditional Chinese medicine. Although its various therapeutic properties, the literature has not yet submitted evidence about H. erinaceus for its effects on the telomerase activity of MCF-7 cells. Methods MCF-7 cells were treated with ethanol, ethanol-water, ether, ethyl acetate, methanol-water, and water extracts to determine the effects on cell viability using the WST8 method. The TeloTAGGG Telomerase PCR ELISA kit was used to assess telomerase activity. Results The water extract was determined to be the most efficient extract to decrease cell viability. The water extract’s half-maximal inhibitory concentration was 250 μg/mL at 72 h. It is found that H. erinaceus has no statistically significant effect compared to positive control on reducing telomerase activity. We found a statistically significant difference in telomerase activity % between H. erinaceus water extracts and negative control (p<0.05). Conclusions Consequently, these differences in telomerase activity are a significant association rather than inferring action. It is considered that water extract shows its cell viability inhibition effects through different mechanisms.

Antioxidative Activities of Micronized Solid-State Cultivated Hericium erinaceus Rich in Erinacine A against MPTP-Induced Damages.

The Lion's mane mushroom (Hericium erinaceus, HE) is a traditional medical mushroom with high nutritional and economic value. HE possesses anticancer, antimicrobial, antioxidant, immunomodulating, neurotrophic, and neuroprotective activities. The present study evaluated the protection and antioxidative activities of micronized mycelium of HE (HEM) in mice treated with 1-methyl-4-phenylpyridinium (MPTP). HEM was cultivated via solid-state fermentation and micronized using cell wall-breaking technology to increase its bioavailability when ingested. Erinacine A, the bioactive compound in the HEM, played a pivotal role in antioxidant defense. We found that micronized HEM could recover the dopamine level in the mice striatum in a dose-dependent manner that had been greatly reduced during MPTP treatment. Moreover, the malondialdehyde (MDA) and carbonyl levels were reduced in the livers and brains of the MPTP + HEM-treated groups compared with the MPTP group. Additionally, antioxidant enzyme activities, including catalase, superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G6PDH), and glutathione reductase (GRd), were elevated after the administration of HEM in MPTP-treated mice in a dose-dependent manner. Taken together, our data indicate that HEM cultivated via solid-state fermentation and processed with cell wall-breaking technology showed an excellent antioxidant efficacy.

High-efficient production of mushroom polyketide compounds in a platform host Aspergillus oryzae

BackgroundOrsellinic acid (2,4-dihydroxy-6-methylbenzoic acid, OA) and its structural analog o-Orsellinaldehyde, have become widely used intermediates in clinical drugs synthesis. Although the research on the biosynthesis of such compounds has made significant progress, due to the lack of suitable hosts, there is still far from the industrial production of such compounds based on synthetic biology.ResultsWith the help of genome mining, we found a polyketide synthase (PKS, HerA) in the genome of the Hericium erinaceus, which shares 60% amino acid sequence homology with ArmB from Armillaria mellea, an identified PKS capable of synthesizing OA. To characterize the function of HerA, we cloned herA and heterologously expressed it in Aspergillus oryzae, and successfully detected the production of OA. Subsequently, the introduction of an incomplete PKS (Pks5) from Ustilago maydis containing only three domains (AMP-ACP-R), which was into herA-containing A. oryzae, the resulted in the production of o-Orsellinaldehyde. Considering the economic value of OA and o-Orsellinaldehyde, we then optimized the yield of these compounds in A. oryzae. The screening showed that when maltose was used as carbon source, the yields of OA and o-Orsellinaldehyde were 57.68 mg/L and 15.71 mg/L respectively, while the yields were 340.41 mg/Kg and 84.79 mg/Kg respectively in rice medium for 10 days.ConclusionsHerein, we successfully expressed the genes of basidiomycetes using A. oryzae heterologous host. As a fungus of ascomycetes, which not only correctly splices genes of basidiomycetes containing multiple introns, but also efficiently produces their metabolites. This study highlights that A. oryzae is an excellent host for the heterologous production of fungal natural products, and has the potential to become an efficient chassis for the production of basidiomycete secondary metabolites in synthetic biology.Graphical

Changes in the structure of polysaccharides under different extraction methods

Changes in the structure of polysaccharides under different extraction methods

Hericium erinaceus Promotes Anti-Inflammatory Effects and Regulation of Metabolites in an Animal Model of Cerebellar Ataxia.

Cerebellar ataxia is a neurodegenerative disorder with no definitive treatment. Although previous study demonstrated the neuroprotective effects of Hericium erinaceus (H.E.), the mechanisms of H.E. treatment on the neuroinflammatory response, neurotransmission, and related metabolites remain largely unknown. We demonstrated that 3-AP rats treated with 25 mg/kg H.E. extracts had improved motor coordination and balance in the accelerated rotarod and rod tests. We showed that the H.E. treatment upregulated the expression of Tgfb1, Tgfb2, and Smad3 genes to levels comparable to those in the non-3-AP control group. Interestingly, we also observed a significant correlation between Tgfb2 gene expression and rod test performance in the 3-AP saline group, but not in the non-3-AP control or H.E.+3-AP groups, indicating a relationship between Tgfb2 gene expression and motor balance in the 3-AP rat model. Additionally, we also found that the H.E. treatment increased mitochondrial COX-IV protein expression and normalized dopamine-serotonin neurotransmission and metabolite levels in the cerebellum of the H.E.+3-AP group compared to the 3-AP saline group. In conclusion, our findings suggest that the H.E. treatment improved motor function in the 3-AP rat model, which was potentially mediated through neuroprotective mechanisms involving TGFB2-Smad3 signaling via normalization of neurotransmission and metabolic pathways.

Solid-State Fermentation of Soybean Meal with Edible Mushroom Mycelium to Improve Its Nutritional, Antioxidant Capacities and Physicochemical Properties

Soybean meal is a class of by-products obtained from the processing of soybean products. Despite its high nutritional value, the presence of glycoside isoflavones limits human use of soybean meal. This study evaluated the effect of solid-state fermentation (SSF) with different edible mushroom mycelia (Pleurotus ostreatus, Hericium erinaceus, and Flammulina velutipes) on the proximate composition, antioxidant properties, and physicochemical properties of fermented soybean meal powder (SP). The results revealed that fermented SP had a higher nutritional value when compared to SP. P. ostreatus was the most pronounced among the three species. Crude protein content was found to have increased by 9.49%, while the concentration of glutamate and aspartic acid increased by 23.39% and 23.16%, respectively. SSF process significantly increased the total polyphenol content (TPC) and aglycone isoflavone content by 235.9% and 324.12%, respectively, resulting in increased antioxidant activity (evaluated by the DPPH, •OH, ABTS+ assays). Microstructural changes in fermented SP and nutrient degradation and utilization were observed. Thus, fermented SP can be used as a raw material with enhanced nutritional properties to develop new functional foods, such as plant-based foods represented by plant meat. It provides a promising approach for increasing the added value of soybean meal.

Protective effects of peptide KSPLY derived from Hericium erinaceus on H2O2-induced oxidative damage in HepG2 cells

Reactive oxygen species (ROS)-induced oxidative damage is strongly associated with the pathogenesis of chronic diseases, and natural antioxidant peptides have good abilities of scavenging ROS. The antioxidant activity of peptide Lys-Ser-Pro-Leu-Tyr (KSPLY) derived from Hericium erinaceus remains unclear. In the present study, the antioxidant effect and mechanism of KSPLY on H2O2-induced oxidative damage in HepG2 cells were investigated. The results indicated that KSPLY exhibited the antioxidant capacity in H2O2-induced HepG2 cells by enhancing superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities. In comparison with the H2O2-treated damage group, the apoptosis rate, ROS level, and malondialdehyde (MDA) content of HepG2 cells treated with KSPLY were significantly decreased. The H. Erinaceus-derived peptide KSPLY pretreatment promoted the expression of detoxification and antioxidant enzymes via the Keap1/Nrf2 signal pathway, thereby inhibiting the generation of ROS and MDA. In conclusion, the H. erinaceus-derived peptide KSPLY effectively protected HepG2 cells against H2O2-induced oxidative damage, and it provided a theoretical basis for the further development of new natural antioxidants.

Lion’s Mane (Hericium erinaceus): A Potential Treatment for Neurologic Disorders in Veterinary Medicine

The use of the culinary and medicinal mushroom Lion’s Mane (LM) (Hericium erinaceus) has been extensively researched. Much of the recent research has been fueled by interest in using LM to prevent and treat neurological diseases such as cognitive decline, dementia, Parkinson’s disease, and Alzheimer’s disease and to stimulate peripheral nerve regeneration. This mushroom is rich in physiologically important components. The main bioactive phytochemicals extracted from LM’s fruiting body and mycelia are hericenones, erinacines, polysaccharides, and dilinoleoyl-phosphatidylethanolamine (DLPE). β-glucan polysaccharides are immuno-active and responsible for LM’s anti-cancer, immunomodulating, hypo-lipidemic, antioxidant, and neuroprotective actions. The hericenones and erinacines can cross the blood-brain barrier and stimulate nerve growth factor (NGF). Since NGF keeps the brain and nervous system regenerating and repairing itself, research has been focused on the effect of these compounds on brain and nervous system conditions. In veterinary medicine, supplementation of LM has potential in the treatment of many conditions, including peripheral nerve damage, dementia, cognitive decline, anxiety, and spinal cord trauma and degeneration.

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.

Use of Hericium erinaceus as a potential therapeutic of mental disorders: a systematic review

Introduction: Hericium erinaceus (HE), often known as Lion's Mane, is an edible fungus that has been extensively explored for its many functions. The use of this mushroom in traditional Chinese medicine dates back many years, and it is now being tested in the treatment of cognitive decline and Alzheimer's disease, and mental diseases like depression, anxiety, schizophrenia. Methods: We followed 2020 PRISMA statement for systematic reviews. The three selected databases were Worldcat®, Cochrane Library®, and PubMed®. On March 7, 2022, a search for articles was conducted. The search sources' descriptions were Hericium erinaceus AND (mental disorders OR cognitive impairment OR depression OR anxiety). "English" was the sole filter applied to the data sources. Results: Three Japanese randomized double-blind controlled trials were included in the review. Although the data demonstrated that HE can be useful in treating symptoms of cognitive impairment and moderate cognitive impairment, it was not effective in treating depression/anxiety symptoms. Conclusions: More studies are needed in countries besides Japan, lasting at least 12 weeks, since shorter periods do not demonstrate significant improvement of symptoms. Incorporating HE into a patient's daily diet may produce favorable benefits by alleviating cognitive decline.

A comparison of study on intestinal barrier protection of polysaccharides from Hericium erinaceus before and after fermentation

The intestinal barrier protects the host from harmful substances. This paper investigated two polysaccharides extracted from the Hericium erinaceus before and after fermentation (HEP and FHEP). The effects of two polysaccharides on the intestinal barrier were investigated in cell and mice models. The results showed that polysaccharides had a protective effect against acrylamide-induced injury in IEC-6 cell. Compared with HEP, FHEP significantly increased TEER and paracellular permeability (P < 0.05). Both polysaccharides the expression of alter tight junction (TJ) and mucin (MUC) as observed in cell Western Bolt (WB). Polysaccharides also enhance the intestinal barrier function in mice by improving cyclophosphamide induced cytokines level, TJ and MUC expression, and gut microbiota. The results showed that FHEP significantly increased IgA, IgG, and IgM levels while decreasing TNF-, IL-1, and IL-6 levels (P < 0.05). The immunohistochemical results showed that both polysaccharides significantly increased the expression of occludin, ZO-1, ZO-2, claudin-3, claudin-4, MUC2 and decreased claudin-2. In parallel, polysaccharides could alter the composition of the gut microbiota, indicating that increased in Bacteriodetes, Firmicutes and decreased in Klebsiella and Shigella. This work provides important views on the protective effect of fermented polysaccharides on the intestinal barrier, and provides a potential mechanism for the beneficial health properties of these biomacromolecules.

Low Weight Polysaccharide of Hericium erinaceus Ameliorates Colitis via Inhibiting the NLRP3 Inflammasome Activation in Association with Gut Microbiota Modulation.

Ulcerative colitis (UC), one of the typical inflammatory bowel diseases caused by dysregulated immunity, still requires novel therapeutic medicine with high efficacy and low toxicity. Hericium erinaceus has been widely used to treat different health problems especially gastrointestinal sickness in China for thousands of years. Here, we isolated, purified, and characterized a novel low weight polysaccharide (HEP10, Mw: 9.9 kDa) from the mycelia of H. erinaceus in submerged culture. We explored the therapeutic effect of HEP10 on UC and explored its underlying mechanisms. On one hand, HEP10 suppressed the production of TNF-α, IL-1β, IL-6, inducible iNOS, and COX-2 in LPS challenged murine macrophage RAW264.7 cells, as well as in colons from DSS-induced colitis mice. On the other hand, HEP10 treatment markedly suppressed the activation of NLRP3 inflammasome, NF-κB, AKT, and MAPK pathways. Moreover, HEP10 reversed DSS-induced alternation of the gut community composition and structure by significantly increasing Akkermansia muciniphila and also promoting functional shifts in gut microbiota. Structural equation modeling also highlighted that HEP10 can change widely through gut microbiota. In conclusion, HEP10 has a better prebiotic effect than the crude polysaccharides of H. erinaceus, which can be used as a novel dietary supplement and prebiotic to ameliorate colitis.