Unveiling the Chemical Composition and Biofunctionality of Hericium spp. Fungi: A Comprehensive Overview.

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

Hericium VN, an undescribed compound isolated from Hericium erinaceus and its cytotoxic activity on human brain astrocytoma.

Hericium erinaceus is a species of mushroom with high nutritional value that is used mainly as food in tropical countries. Phytochemical study of H. erinaceus led to the isolation of an undescribed compound, named as hericium VN (1), together with nine known compounds, 1-(2-formyl-1-pyrrolyl)butanoic acid (2), herierin III (3), 5'-(methylthio)adenosine (4), adenosine (5), nicotinic acid (6), (22E,24R)-5α,8α-epidioxyergosta-6,9(11),22-trien-3ß-ol (7), 5α,8α-peroxycerevisterol (8), (22E,24R)-5α,8α-epidioxy-egosta-6,22-diene 3-O-ß-D-glucopyranoside (9), and cerevisterol (10) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configuration of compound 1 was determined by experimental combined with calculated electronic circular dichroism spectra. Compound 7 exhibited cytotoxic effects against brain tumor cell line CCF-STTG1 with the IC50 value of 15.50 µM, compared to that of the positive control compound, doxorubicin, which showed IC50 value of 15.84 µM.

The potential therapeutic role of Hericium erinaceus extract in pathologic conditions involving the urogenital-gut axis: insights into the involved mechanisms and mediators.

In this review we focused on the putative therapeutic effect of Hericium erinaceus extract in the treatment of pathologic conditions of the lower urinary tract in which intestinal inflammation may play a role. To this aim we reviewed the available evidence on pelvic cross-organ sensitization as a possible mechanism through which intestinal inflammation and dysbiosis may affect the lower urinary tract. Also, we reviewed the clinical and experimental evidence supporting the role of Hericium erinaceus extract as an anti-inflammatory agent highlighting the role of a number of putative mediators and mechanisms which might make this nutraceutical suitable for the management of 'difficult to treat' lower urinary tract disorders.

Polysaccharides from an edible mushroom, Hericium erinaceus, alleviate ulcerative colitis in mice by inhibiting the NLRP3 inflammasomes and reestablish intestinal homeostasis.

This study aimed to assess the effects of polysaccharides extracted from Hericium erinaceus fruiting bodies (HEFPs) on the inflammatory response to oxidative stress in a mouse model of ulcerative colitis (UC) induced by ingestion of dextran sodium sulfate. The results indicated reduced oxidative damage in the HEFPs groups, as evidenced by significantly decreased malondialdehyde levels and significantly increased levels of the antioxidant enzymes superoxide dismutase and catalase in colon homogenates, compared with those in the Model Control (MC) group. Additionally, compared with the levels in the MC group, the levels of the pro-inflammatory factors IL-6, IL-1ß, and TNF-α in the positive-control (PC) and HEFPs groups were significantly lower, and that of the anti-inflammatory factor IL-10 was significantly higher. qRT-PCR analyses revealed that the colon expression patterns of IL-6, IL-1ß, TNF-α, and IL-18 were consistent with the serum levels. Western-blotting results indicated significantly lower levels of NLRP3, ASC, and caspase 1 P20 in the HEFPs and PC groups than in the MC group. These findings suggest that HEFPs alleviate UC by suppressing the NLRP3 inflammasome/Caspase-1 pathway. Lachnospiraceae, Clostridiales, Parabacteroides, Oscillibacter, and Clostridium XlVa genera were more abundant in the gut microbiota of the HEFPs group than that of the MC group.

Effects of Hericium erinaceus polysaccharide in porcine IPEC-J2 intestinal epithelial cells against apoptosis induced by oxidative stress.

This study was intended to investigate whether Hericium erinaceus polysaccharides (HEP) prevent oxidative stress and apoptosis of intestinal porcine epithelial cells from jejunum (IPEC-J2 cells) induced by hydrogen peroxide (H2O2). Crude HEP were extracted and purified by chromatography. The ultraviolet and infrared spectra and monosaccharide composition of HEP were analyzed. Reactive oxygen species (ROS) generation was quantified by flow cytometry method, and lactate dehydrogenase (LDH) and malondialdehyde (MDA) production were determined by TBARS. Also, apoptosis was analyzed by flow cytometry method and the apoptosis-related regulatory molecules were determined by microplate or western blotting method. Our results showed that pretreatment of IPEC-J2 cells with HEP significantly scavenged ROS and reduced LDH and MDA production. HEP also reduced apoptosis and kept polarity of the mitochondrial membrane potential. Moreover, HEP increased the content of caspase-3 and PARP, and protein expression of Bcl-2, while inhibited Bax and Bad and reduced the content of caspase-9 and release of CytC. Meanwhile, HEP inhibited the protein expression of TNFR1, FAS, and FASL, and decreased the content of caspase-8. The results indicated that HEP had a protective effect against oxidative stress in IPEC-J2 cells and the underlying mechanism was reducing apoptosis via mitochondrial and death receptor pathways.

Resveratrol-loaded sulfated Hericium erinaceus ß-glucan-chitosan nanoparticles: Preparation, characterization and synergistic anti-inflammatory effects.

Resveratrol (RES) is a natural polyphenol with excellent biological activity. But the poor stability and bioavailability of RES severely limit its application. Thus, the resveratrol-loaded sulfated Hericium erinaceus ß-glucan-chitosan nanoparticles (DS-CS-RES NPs) were prepared using electrostatic self-assembly to solve these problems in this study. The structure of DS-CS-RES NPs was spherical or sub spherical shape with small average particle size (191.07 nm), which was characterized by FT-IR, FS, XRD and TEM. DS-CS-RES NPs exhibited good stability and RES had a sustainable release from the nanoparticles in gastrointestinal digestion. Meanwhile, DS-CS-RES NPs could improve the inflammatory injury of LPS stimulated RAW264.7 macrophages by inhibiting the production of NO, IL-1ß, IL-6 and TNF-α. Furthermore, DS-CS-RES NPs had strong anti-inflammatory activity by regulating protein levels of NF-κB p65, STAT1 and TLR4 through NF-κB and JAK-STAT1 signaling pathway in vitro, and sulfated H. erinaceus ß-glucan-chitosan nanoparticle (DS-CS NPs) and RES had synergistic anti-inflammatory effect. Overall, DS-CS NPs can serve as a potential green and safe functional carrier for encapsulating resveratrol, which can improve its anti-inflammatory activity. This work may be conducive to the development of functional carrier for encapsulating RES and applications of hydrophobic active molecules in functional foods or medicines.

Discovery of a New Compound, Erinacerin W, from the Mycelia of Hericium erinaceus, with Immunomodulatory and Neuroprotective Effects.

One new compound with an isoindolinone skeleton, along with erinacines A, C, and S, was isolated from the mycelia of Hericium erinaceus, an edible fungus with a long history of use in traditional Chinese medicine. Based on analysis of MS and NMR spectral data, the structure of the compound was identified as (2E,6E)-8-(2-(1-carboxy-3-methylbutyl)-4,6-dihydroxy-1-oxoisoindolin-5-yl)-2,6-dimethylocta-2,6-dienoic acid. In light of this discovery, we have given this compound the name erinacerin W. Using a co-culture in vitro LPS-activated BV2 microglia-induced SH-SY5Y neuroinflammation model, the results showed that erinacerin W demonstrated protection against the LPS-activated BV-2 cell-induced overexpression of IL-6, IL-1ß, and TNF-α on SH-SY5Y cells. This finding may provide potential therapeutic approaches for central nervous disorders.

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-1ß 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.

Effects of different extraction methods on the structural and biological properties of Hericium coralloides polysaccharides.

In current study, polysaccharides from Hericium coralloides were extracted by heat reflux, acid-assisted, alkali-assisted, enzyme-assisted, ultrasonic-assisted, cold water, pressurized hot water, hydrogen peroxide/ascorbic acid system and acid-chlorite delignification methods, which were named as HRE-P, ACE-P, AAE-P, EAE-P, UAE-P, CWE-P, PHE-P, HAE-P, and ACD-P, respectively. Their physicochemical properties, structural characteristics, and antioxidant activities were investigated and compared. Experimental outcomes indicated notable variations in the extraction yields, chemical compositions, monosaccharide constituents and molecular weights of the obtained nine polysaccharides. HRE-P demonstrated the highest activity against ABTS and OH radicals, CWE-P against ABTS, DPPH, and superoxide radicals, and UAE-P against DPPH radicals. In addition, UAE-P, CWE-P, and HAE-P exhibited better protective effects on L929 cells, when compared to the other obtained polysaccharides. Additionally, correlation analysis indicated that monosaccharide composition and total polyphenol content were two prominent variables influencing the bioactivity of H. coralloides polysaccharides.

Secretory Production of the Hericium erinaceus Laccase from Saccharomyces cerevisiae.

Mushroom laccases play a crucial role in lignin depolymerization, one of the most critical challenges in lignin utilization. Importantly, laccases can utilize a wide range of substrates, such as toxicants and antibiotics. This study isolated a novel laccase, named HeLac4c, from endophytic white-rot fungi Hericium erinaceus mushrooms. The cDNAs for this enzyme were 1569 bp in length and encoded a protein of 523 amino acids, including a 20 amino-acid signal peptide. Active extracellular production of glycosylated laccases from Saccharomyces cerevisiae was successfully achieved by selecting an optimal translational fusion partner. We observed that 5 and 10 mM Ca2+, Zn2+, and K+ increased laccase activity, whereas 5 mM Fe2+ and Al3+ inhibited laccase activity. The laccase activity was inhibited by the addition of low concentrations of sodium azide and L-cysteine. The optimal pH for the 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt was 4.4. Guaiacylglycerol-ß-guaiacyl ether, a lignin model compound, was polymerized by the HeLac4c enzyme. These results indicated that HeLac4c is a novel oxidase biocatalyst for the bioconversion of lignin into value-added products for environmental biotechnological applications.

The ethnopharmacology, phytochemistry and pharmacology of the genus Hericium.

ETHNOPHARMACOLOGICAL RELEVANCE: Mushrooms in the genus Hericium are used as functional food and traditional medicines for a long history in East Asian countries such as China, India, Japan, and Korea. Some species of Hericium are called as monkey head mushroom (Houtougu) in China and Yamabushitake in Japan, which are traditionally considered as rare and precious health promoting food and medicinal materials for the treatment of dyspepsia, insomnia, chronic gastritis, and digestive tract tumors. THE AIM OF THE REVIEW: This review aims to summarize the ethnopharmacology and structural diversity of secondary metabolites from Hericium species, as well as the pharmacological activities of the crude extracts and pure compounds from Hericium species in recent years. MATERIALS AND METHODS: All the information was gathered by searching Scifinder, PubMed, Web of Science, ScienceDirect, Springer, Wiley, ACS, CNKI, Baidu Scholar, Google Scholar databases and other published materials (books and Ph.D. and M. Sc. Dissertations) using the keywords "Hericium", "Traditional uses", "Chemical composition", "Quality control" and "Pharmacological activity" (1971-May 2023). The species name was checked with https://www.mycobank.org/. RESULTS: The traditional uses of Hericium species were summarized, and 230 secondary metabolites from Hericium species were summarized and classified into six classes, mainly focusing on their chemical diversity, biosynthesis, biological activities. The modern pharmacological experiments in vivo or in vitro on their crude and fractionated extracts showed that the chemical components from Hericium species have a broad range of bioactivities, including neuroprotective, antimicrobial, anticancer, α-glucosidase inhibitory, antioxidant, and anti-inflammatory activities. CONCLUSIONS: The secondary metabolites discovered from Hericium species are highly structurally diverse, and they have the potential to be rich resources of bioactive fungal natural products. Moreover, the unveiled bioactivities of their crude extracts and pure compounds are closely related to critical human health concerns, and in-depth studies on the potential lead compounds, mechanism of pharmacological effects and pharmaceutical properties are clearly warranted.

Evaluation of the "Relative Ordered Structure of Hericium erinaceus Polysaccharide" from Different Origins: Based on Similarity and Dissimilarity.

Polysaccharides are organic compounds widely distributed in nature, but structural order and disorder remain a formidable problem. In this study, based on the theoretical framework of the "relative ordered structure of polysaccharide" proposed in our previous work, the structural order of Hericium erinaceus polysaccharides from different regions was evaluated by FT-IR, methylation analysis, and 1H NMR spectroscopy combined with chemometric methods. The results of principal component analysis and heatmap cluster analysis revealed that 18-subfractions exhibit four different structural types with representative glycoside linkage types: fucogalactoglucan, glucofucogalactan, fucoglucan, and glucan. The main chain of heteroglucans often consists of ß-(1 → 6)-Glcp, ß-(1 → 4)-Glcp, and ß-(1 → 3)-Glcp residues, which are predominantly substituted at the O-3 and O-6 positions. The main chain structure of heterogalactans is α-(1 → 6)-Galp residues, which may be replaced by Fucp and Galp residues at O-2. Overall, our findings demonstrate the validity of the "relative ordered structure of polysaccharide" in Hericium erectus polysaccharides and simplify the complexity of polysaccharide structures.

Commercial scale production of Yamabushitake mushroom (Hericium erinaceus (Bull.) Pers. 1797) using rubber and bamboo sawdust substrates in tropical regions.

Yamabushitake (Hericium erinaceus) is one of the most sought out mushrooms that is widely used for both direct consumption and medicinal purposes. While its demand increases worldwide, cultivation of the mushroom is limited to temperate areas and its production in tropical regions has never been explored. The aim of this study was to test the utilization of rubber and bamboo sawdust, alone or as a substrate mixture, for industrial scale Yamabushitake mushroom production. Five substrate treatments with various ratios of the two sawdust were compared for their physicochemical properties in relation to mushroom productivity. The highest mushroom fresh and dry (113.22 and 23.25 g, respectively), biological efficiency (42.61%), and cap size (9.53 cm) were obtained from the substrates containing 100% rubber sawdust, with the mushroom yield decreasing proportional to the ratio of bamboo sawdust. The 100% rubber sawdust substrate provided a higher initial organic matter and carbon content together with C:N ratio at 63.2%, 36.7% and 65.48, respectively, whereas the 100% bamboo sawdust provided higher nitrogen content (1.03%), which was associated with lower mushroom yield but higher number of fruiting bodies. As in the 100% rubber sawdust substrate, a comparable mushroom yield and growth attributes were also obtained in the 3:1 rubber-bamboo sawdust mixture substrate. Principle component analysis of the measured variables indicated a strong influence of substrate C:N ratio before spawning and the change in substrate electrical conductivity and N content after cultivation to the variation in mushroom productivity among the treatments. The results demonstrate the applicability of rubber sawdust and its combination with up to 25% of bamboo sawdust for Yamabushitake mushroom cultivation and provide the basis for substrate optimization in the tropical Yamabushitake mushroom industry through a circular economy framework.

Hericioic Acids A-G and Hericiofuranoic Acid; Neurotrophic Agents from Cultures of the European Mushroom Hericium flagellum.

Neurodegenerative diseases are currently posing huge social, economic, and healthcare burdens among the aged populations worldwide with few and only palliative treatment alternatives available. Natural products continue to be a source of a vast array of potent neurotrophic molecules that could be considered as drug design starting points. The present study reports eight new isoindolinone and benzofuranone derivatives, for which we propose the trivial names, hericioic acids A-G (1-7) and hericiofuranoic acid (8), which were isolated from a solid culture (using rice as substrate) of the rare European edible mushroom Hericium flagellum. The chemical structures of these compounds were determined based on extensive 1D and 2D NMR spectroscopy along with HRESIMS analyses. The isolated compounds were assessed for their neurotrophic activity in rat pheochromocytoma cells (PC-12) to promote neurite outgrowth on 5 ng NGF supplementation; all the compounds increased neurite outgrowths, with compounds 3, 4, and 8 exhibiting the strongest effects.

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.

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.

Hericium caput-medusae (Bull.:Fr.) Pers. fermentation concentrate polysaccharides improves intestinal bacteria by activating chloride channels and mucus secretion.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional edible fungus in China and many other Asian countries, Hericium caput-medusae (Bull. Fr.) Pers. is widely used to improve the health of the gastrointestinal tract. For example, the drug "Weilexin Granules" is mainly composed of H. caput-medusae (Bull. Fr.) Pers. fermentation concentrate. However, the mechanism of action remains to be elucidated. AIMS OF THE STUDY: The purpose of this study was to assess whether polysaccharides from H. caput-medusae (Bull. Fr.) Pers. fermentation concentrate (HFP) exerts a gut protective effect and a regulatory effect on the intestinal microbiota through the chloride channels and mucus secretion. MATERIALS AND METHODS: HFP was extracted, characterized and different concentrations of HFP (100, 200, 400 mg/kg) were administered to mice for 14 days. The changes in gut microbiota were observed via 16S high throughput sequencing. Short-chain fatty acids (SCFAs) was detected by GC-MS. AB-PAS staining was used to observe the secretion of mucus. The chloride channel activity and protein expression were verified by short-circuit current measurement and Western blot. RESULTS: HFP regulated the abundance of gut microbiota in mice, with increased levels of Ruminococcaceae and Lachnospiraceae and reduced proportions of Staphylococcus and Enterobacter. HFP enhanced mucus volume as well as increased intestinal fluid secretion by activating the chloride channels. In addition, short-circuit current experiments also proved that HFP activates Cl⁻ currents targeting cystic fibrosis transmembrane conductance regulator (CFTR) and Anoamin1 (ANO1). CONCLUSION: In conclusion, HFP might increase intestinal fluid secretion by promoting Cl⁻ secretion, which in turn advanced mucus hydration as well as regulated gut microbiota to improve intestinal health. Therefore, H. caput-medusae (Bull. Fr.) Pers. could be potentially used in the regulation of intestinal secretion and microbes.

Ameliorating Effect of the Edible Mushroom Hericium erinaceus on Depressive-Like Behavior in Ovariectomized Rats.

Estrogen deficiency during menopause causes a variety of neurological symptoms, including depression. The edible Lion's Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (HE), is a medicinal mushroom that has the potential for a neuroprotective effect and ameliorating neurological diseases, such as depression, anxiety, and neurodegenerative diseases. HE contains phytoestrogens, including daidzein and genistein. However, the ameliorating effect of HE on menopausal symptoms is not well understood. Here we investigated the impact of methanol extract of the HE fruiting body on depressive-like behavior in postmenopausal model rats. The activation of estrogen receptor alpha (ERα) causes body weight loss and uterine weight gain. Body weight gain and uterine weight loss by estrogen deficiency in ovariectomized (OVX) rats were reversed with 17ß-estradiol (E2) but not with HE. Thus, the phytoestrogens in HE may hardly activate ERα. Estrogen receptor beta (ERß) is expressed in the brain, and activation of ERß ameliorates menopausal depressive symptoms. Notably, depressive-like behavior in OVX rats evaluated in forced swim test was reduced by administration of not only E2 but also HE for 92 d. Long-term activation of ERα increases the risk of breast and uterine cancers. HE, therefore, may be effective in treating menopausal depression without the risk of carcinogenesis caused by ERα activation.

Polysaccharides from Hericium erinaceus Fruiting Bodies: Structural Characterization, Immunomodulatory Activity and Mechanism.

Five fractions from crude Hericium erinaceus polysaccharides (HEPs), including HEP-1, HEP-2, HEP-3, HEP-4 and HEP-5, were obtained through column chromatography with a DEAE Cellulose-52 column and Sephadex G-100 column. The contents of total carbohydrates and uronic acid in HEPs were 53.36% and 32.56%, respectively. HEPs were mainly composed of Fuc, Gal and Glu in a molar ratio of 7.9:68.4:23.7. Its chemical structure was characterized by sugar and methylation analysis, along with 1H and 13C NMR spectroscopy. HEP-1 contains the backbone composed of (1→6)-linked-galactose with branches attached to O-2 of some glucose. The immunological activity assay indicated that HEP-1 significantly promoted the production of nitric oxide, interleukin-6, interleukin-10, interferon-γ and tumor necrosis factor-α and the phosphorylation of signaling molecules. Collectively, these results suggested that HEP-1 could improve immunity via NF-κB, MAPK and PI3K/Akt pathways. Hericium erinaceus polysaccharides might be explored as an immunomodulatory agent for use in dietary supplements.

Improvement of extraction from Hericium erinaceus on the gut-brain axis in AD-like mice.

In this study, results showed the extractions of Hericium erinaceus can ameliorate the learning and memory abilities significantly, reduce the swelling of brain tissues, neuronal apoptosis, and down-regulate the expression of Alzheimer's disease intracellular markers including Tau and Aß1-42. 16S rRNA sequencing of gut microbiota indicated that the extractions maintained the diversity and stability of the microbial community, rebalanced the ratio of Firmicutes/Proteobacteria, increased the abundance of some probiotics such as Lactobacillus and Akkermansia, and reduced some pathogenic bacteria and opportunistic pathogenic bacteria such as Enterobacteriaceae. In addition, Akkermanisa, Blautia, Oscillospira, Dehalobacterium, Ackermansia, Allobaculum and Coprococcus were up-regulated, and these bacteria have the effect of anti-intestinal inflammation.Some genera with inhibitory effects on inflammation, such as Desulfovibrio, Alistipes and Rikenellaceae, were down-regulated. Deep studies showed that multi-target compounds from Hericium erinaceus could target the gut microbiota, regulate the metabolism, inflammation, immunity and insulin to slow the progression of Alzheimer's disease. The results suggested that extractions from Hericium erinaceus could be formulated as dietary supplement or/and drug treatments against Alzheimer's disease. However, these pharmacologically active ingredients and mode of action require clinical studies.