Selective impact of three homogenous polysaccharides with different structural characteristics from Grifola frondosa on human gut microbial composition and the structure-activity relationship.

Natural polysaccharides interact with gut microbes to enhance human well-being. Grifola frondosa is a polysaccharides-rich edible and medicinal mushroom. The prebiotic potential of G. frondosa polysaccharides has been explored in recent years, however, the relationship between their various structural features and prebiotic activities is poorly understood. In this study, three homogenous polysaccharides GFP10, GFP21 and GFP22 having different molecular weights (Mw), monosaccharide compositions and glycosidic linkages were purified from G. frondosa, and their effects on intestinal microbial composition were compared. GFP10 was a fucomannogalactan with an Mw of 23.0 kDa, and it selectively inhibited Enterobacter, while GFP21 was a fucomannogalactoglucan with an Mw of 18.6 kDa, and it stimulated Catenibacterium. GFP22 was a 4.9 kDa mannoglucan that selectively inhibited Klebsiella and boosted Bifidobacterium, Catenibacterium and Phascolarctobacterium, and prominently promoted the production of short-chain fatty acids (SCFAs). The selective modulation of gut microbiota by polysaccharides was structure-dependent. A relatively lower Mw and a high proportion of glycosidic linkages like T-Glcp, 1,3-Glcp, 1,3,6-Glcp and 1,4-Glcp might be more easily utilized to produce SCFAs and beneficial for the proliferation of Catenibacterium and Phascolarctobacterium. This research provided a valuable resource for further exploring the structure-activity relationship and prebiotic activity of G. frondosa polysaccharides.

Selenochemical modification of low molecular weight polysaccharides from Grifola frondosa and the mechanism of their inhibitory effects on gastric cancer cells.

An important micronutrient involved in immune response and antitumor is selenium. LMW-GFP, a polysaccharide extracted from Grifola frondosa seed bodies, has a relatively weak antitumor effect on BGC-823 and MFC cells in vitro, whereas selenium binding to LMW-GFP can significantly increase the in vitro antitumor activity of LMW-GFP. In this study, Se-LMW-GFP was prepared by the HNO3-Na2SeO3 method, and the structures of LMW-GFP and Se-LMW-GFP were characterized by UV-visible spectroscopy of absorption, FTIR spectroscopy, and electron scanning microscopy, and these structural analyses showed that selenium was successfully complexed to LMW-GFP. The selenium content of Se-LMW-GFP was measured to be 2.08 % ± 0.08 % by ICP-MS. The anti-tumor activity of LMW-GFP before and after selenium modification was compared by cellular experiments, and the findings indicated that the anti-tumor activity of Se-LMW-GFP was considerably improved over that of LMW-GFP, and inhibited the proliferation of BGC-823 cells and MFC cells through a combination of the Fas/FasL-mediated exogenous death receptor pathway as well as the endogenous mitochondrial pathway. Our results suggest that Se-LMW-GFP not only has great potential for natural health food and anti-gastric cancer drug development but is also a good selenium supplement.

Isolation and identification of active components from Grifola frondosa and its anti-EV71 virus effect.

BACKGROUND: It is reported that anti-enterovirus 71 (EV71) drugs have some side effects on human health. Notably, fungi plays a crucial role in promoting human health and anti-virus. Grifola frondosa is a type of large medicinal and edible fungi, rich in active substances. The present study aimed to investigate the anti-EV71 effect of G. frondosa and the potential active substances. RESULTS: In the present study, the water extract of G. frondosa was subjected to ethanol precipitation to obtain the water-extracted supernatant of G. frondosa (GFWS) and water-extracted precipitation of G. frondosa. Their inhibitory effects on EV71 virus were studied based on a cell model. The results showed that GFWS had stronger security and anti-EV71 effects. In addition, the chemical constituents of GFWS were identified by ultra-high performance liquid chromatography-tandem mass spectrometry, which were selected for further separation and purification. Three compounds, N-butylaniline, succinic acid and l-tryptophan, were isolated from GFWS by NMR spectroscopy. It is noteworthy that N-butylaniline and l-tryptophan were isolated and identified from the G. frondosa fruiting bodies for the first time. Our study found that l-tryptophan has anti-EV71 virus activity, which reduced EV71-induced apoptosis and significantly inhibited the replication process after virus adsorption. Furthermore, it could also bind to capsid protein VP1 to prevent the virus from attaching to the cells. CONCLUSION: l-tryptophan was an inhibitor of the EV71 virus, which could be used in infant nutrition and possibly provide a new drug to treat hand, foot and mouth disease. © 2024 Society of Chemical Industry.

Grifola frondosa polysaccharides: A review on structure/activity, biosynthesis and engineering strategies.

Polysaccharides are the main polymers in edible fungi Grifola frondosa, playing a crucial role in the physiology and representing the healthy benefits for humans. Recent efforts have well elucidated the fine structures and biological functions of G. frondosa polysaccharides. The recently-rapid developments and increasing availability in fungal genomes also accelerated the better understanding of key genes and pathways involved in biosynthesis of G. frondosa polysaccharides. Herein, we provide a brief overview of G. frondosa polysaccharides and their activities, and comprehensively outline the complex process, genes and proteins corresponding to G. frondosa polysaccharide biosynthesis. The regulation strategies including strain improvement, process optimization and genetic engineering were also summarized for maximum production of G. frondosa polysaccharides. Some remaining unanswered questions in describing the fine synthesis machinery were also pointed out to open up new avenues for answering the structure-activity relationship and improving polysaccharide biosynthesis in G. frondosa. The review hopefully presents a reasonable full picture of activities, biosynthesis, and production regulation of polysaccharide in G. frondosa.

Structural characterization and immunomodulatory effect of a starch-like Grifola frondosa polysaccharides on cyclophosphamide-induced immunosuppression in mice.

In this study, a pure Grifola frondosa polysaccharide (GFP-1) was extracted and purified from Grifola frondosa. By HPLC, GC-MS, FT-IR, and NMR analysis, GFP-1 was determined to be a starch-like polysaccharide with an average molecular weight of 3370 kDa. It included three monosaccharides, i.e., glucose, galactose, and mannose. The backbone of GFP-1 consisted of →4)-α-Glcp-(1→ and →4,6)-α-Glcp-(1 â†’ . The side branches were composed of →6)-α-Galp-(1→, α-Glcp-(1→, and a small amount of α-Manp-(1 â†’ . By using a cyclophosphamide (CTX)-induced immunosuppressed mice model, we evaluated the immunomodulatory activity of GFP-1. The results showed that GFP-1 increased the thymic and spleen indices, promoted the level of IgG and IgA in serum, and activated the mitogen-activated protein kinase (MAPK) pathway in CTX-induced mice. Also, GFP-1 significantly promoted the mRNA expression of intestinal barrier factors and protected intestinal structural integrity in immunosuppressed mice. In conclusion, the data presented here suggested that GFP-1 might be a potential immune-enhancing supplement.

Anti-α-glucosidase, Anti-proliferative and Anti-enterovirus 71 Activity of Secondary Metabolites Identified from Grifola Frondosa.

Grifola frondosa, an edible and medicinal resource, is widely used as functional foods worldwide. To explore bioactive compounds against α-glucosidase, human tumor cells and enterovirus 71 (EV71), eight compounds were isolated from G. frondosa by chromatographic column. Among the isolated compounds, heptadecanoic acid, uridine and adenosine exhibited potent inhibition activity against α-glucosidase, ergosterols and ergosterol-5,8-peroxide showed anti-proliferative activity on tumor cells, while ergosterol and methyl linoleate displayed inhibition against the replication of EV71. Also, to our knowledge, this is the first study to report that fatty acids isolated from G. frondosa show potent inhibition against α-glucosidase and EV71. Further molecular docking results revealed that the active compounds in G. frondosa form hydrogen bonding, hydrophobic interactive and π-stacking with the active sites on the surface of α-glucosidase, CASP3 and VP1 proteins, thus promoting the active compounds to combine with the target protein to form a stable complex, thus playing an antagonistic role. Our results could provide a new active compound and mode of action for G. frondosa to treat diabetes, cancer and EV71-infected patients.

Gastrointestinal metabolism characteristics and mechanism of a polysaccharide from Grifola frondosa.

Grifola frondosa polysaccharide (GFP) is mainly composed of α-1,4 glycosidic bonds and possesses multiple pharmacological activities. However, the absence of pharmacokinetic studies has limited its further development and utilization. Herein, GFP was labeled with 5-DTAF (FGFP) and cyanine 5.5 amine (GFP-Cy5.5) to investigate its gastrointestinal metabolism characteristics and mechanism. Significant distributions of the polysaccharide in the liver and kidneys were observed by near infrared imaging. To investigate the specific distribution form of the polysaccharide, in vitro digestion models were constructed and revealed that FGFP was degraded in saliva and rat small intestine extract. The metabolites were detected in the stomach and small intestine, followed by further degradation in the distal intestine in the in vivo experiment. Subsequent investigations showed that α-amylase was involved in the gastrointestinal degradation of GFP, and its metabolite finally entered the kidneys, where it was excreted directly with urine.

Research Themes and Trends of Hen of the Woods or Maitake Medicinal Mushroom Grifola frondosa (Agaricomycetes): A Bibliometric Analysis of the Knowledge Field.

This paper aims to characterize the knowledge field of Grifola frondosa and analyze its research themes and trends. CiteSpace, a powerful bibliometric analysis tool, was adopted to visualize the knowledge field of G. frondosa research for facilitating this current study. A total of 747 articles and reviews retrieved from the Web of Science Core Collection (WoSCC) database between 1998 and 2022 were analyzed by CiteSpace. It was found that China and Japan are the most influential countries in G. frondosa research. Secondly, polysaccharide, bioactivity, structural characterization, and submerged culture are the main themes of G. frondosa research, among which bioactivity and structural characterization are the current research hotspots. Finally, selenium polysaccharide and gut microbiota may be the emerging trends in G. frondosa research in the future. This study could help researchers discern the evolution and future trends of G. frondosa research and provide a reference for related research work.

A cold-water extracted polysaccharide-protein complex from Grifola frondosa exhibited anti-tumor activity via TLR4-NF-κB signaling activation and gut microbiota modification in H22 tumor-bearing mice.

Grifola frondosa polysaccharide-protein complex (G. frondosa PPC) is a polymer which consists of polysaccharides and proteins/peptides linked by covalent bonds. In our previous ex vivo research, it has been demonstrated that a cold-water extracted G. frondosa PPC has stronger antitumor activity than a G. frondosa PPC extracted from boiling water. The main purpose of the current study was to further evaluate the anti-hepatocellular carcinoma and gut microbiota regulation effects of two PPCs isolated from G. frondosa at 4 °C (GFG-4) and 100 °C (GFG-100) in vivo. The results exhibited that GFG-4 remarkably upregulated the expression of related proteins in TLR4-NF-κB and apoptosis pathway, thereby inhibiting the development of H22 tumors. Additionally, GFG-4 increased the abundance of norank_f__Muribaculaceae and Bacillus and reduced the abundance of Lactobacillus. Short chain fatty acids (SCFAs) analysis suggested that GFG-4 promoted SCFAs production, particularly butyric acid. Conclusively, the present experiments revealed GFG-4 has the potential of anti-hepatocellular carcinoma growth via activating TLR4-NF-κB pathway and regulating gut microbiota. Therefore, G. frondosa PPCs could be considered as safe and effective natural ingredient for treatment of hepatocellular carcinoma. The present study also provides a theoretical foundation for the regulation of gut microbiota by G. frondosa PPCs.

Maitake Medicinal Mushroom, Grifola frondosa (Agaricomycetes), and Its Neurotrophic Properties: A Mini-Review.

Neurodegeneration is one of the most common manifestations in an aging population. The occurrence of oxidative stress and neuroinflammation are the main contributors to the phenomenon. Neurologic conditions such as Alzheimer's disease (AD) and Parkinson's disease (PD) are challenging to treat due to their irreversible manner as well as the lack of effective treatment. Grifola frondosa (Dicks.: Fr.) S.F. Gray, or maitake mushroom, is believed to be a potential choice as a therapeutic agent for neurodegenerative diseases. G. frondosa is known to be a functional food that has a wide variety of medicinal purposes. Thus, this review emphasizes the neuroprotective effects and the chemical composition of G. frondosa. Various studies have described that G. frondosa can protect and proliferate neuronal cells through neurogenesis, antioxidative, anti-inflammatory, and anti-ß-amyloid activities. The mechanism of action behind these therapeutic findings in various in vitro and in vivo models has also been intensively studied. In this mini review, we also summarized the chemical composition of G. frondosa to provide a better understanding of the presence of nutritional compounds in G. frondosa.

Preparation and structural characterization of acid-extracted polysaccharide from Grifola frondosa and antitumor activity on S180 tumor-bearing mice.

In this study, an acid-extracted polysaccharide (GFP-A) was extracted from the fruiting bodies of G. frondosa with 1 % hydrochloric acid solution. Our study aimed to imitate the processes of digestion, absorption and antitumor activities of polysaccharides from G. frondosa under the acid environment of stomach in the body. The preliminary structural analysis resulted that GFP-A (about 1.10 × 106 Da) was a neutral polysaccharide composed of xylose, mannose, glucose (molar ratio: 0.12:1.00:6.98) with α-type glycosidic linkages. Additionally, antitumor activities on S180 tumor-bearing mice showed that GFP-A could effectively inhibit the growth of S180 tumor cells by protecting immune organs (thymus and spleen), activating immune cells (NK cells, lymphocytes and macrophages), upregulating the secretion of serum cytokines (TNF-α, IL-2 and IFN-γ) in vivo. H & E staining and cell cycle determination further demonstrated that GFP-A could induce S180 tumor cells apoptosis via arresting them in G1 phase. These results demonstrated that GFP-A could provide a theoretical basis for treatment of cancer.

Effect of Maitake D-fraction in advanced laryngeal and pharyngeal cancers during concurrent chemoradiotherapy: A randomized clinical trial.

BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is an ideal treatment for advanced head and neck squamous cell carcinoma (HNSCC). The performance of CCRT induces severe toxicities in HNSCC patients and decreases the quality of life (QOL). Maitake D-Fraction is proteoglycan which has anti-tumor function associated with its immunomodulatory capacity. The polysaccharides of Maitake also have anti-radiation effect in radiation therapy during cancer treatment. This research aimed to illustrate Maitake D-Fraction effects on CCRT-associated adverse events and QOL. METHODS: During CCRT, Maitake capsules were taken orally 3 times a day, each time 4 capsules, one hour before meals. QOL were analyzed by EORTC QLQ-C30-Chinese version and EORTC QLQ-HandN-35-Chinese version. 141 patients were recruited and divided into an intervention group and a placebo group. RESULTS: Frequencies of severe CCRT-associated adverse events in intervention group were less than in placebo group. Global QOL score in intervention group was higher than in placebo group 5 weeks post treatment. The proportion of patients returning to baseline global QOL score at 6-month was increased by Maitake D-Fraction administration. CONCLUSION: In conclusion, this randomized clinical trial demonstrated that in advanced laryngeal and pharyngeal cancer patients, the oral administration of Maitake D-Fraction alleviated CCRT-related adverse events and deterioration in QOL.

CD3Ɛ immune restorative ability induced by Maitake Pro4x in immunosupressed BALBc mice.

OBJECTIVES: The aim of this research was to determine if the rich beta glucan compound called Maitake Pro4X can recover the T cell/NK population depleted by Dexamethasone treatment in lymph nodes from cancer-free BALBc female mice. A CD3Ɛ molecular FITC labelled marker was used to measure the effect of Maitake D-Fraction Pro4X (5 mg/kg) on T cell/NK cells populations employing flow cytometry from immunosuppressed female BALBc mice in lymph nodes. There were employed other molecular markers such as CD19, CD105, Ly6G. RESULTS: Maitake Pro4X (5 mg/kg) was able to recover 42.97% of the depleted CD3Ɛ FITC cell population level in Lymph nodes from immunosuppressed female BALBc mice from 4.328 ± 6.229 to 22.646 ± 12.393 (p < 0.01) using Flow Cytometry. Maitake was also able to significantly increase the Ly6G PE cell population with p < 0.05 in lymph nodes.

Effect of low-intensity magnetic field on the growth and metabolite of Grifola frondosa in submerged fermentation and its possible mechanisms.

This study aimed to investigate the effects of low intensity alternating magnetic field on the submerged fermentation of Grifola frondosa, and its possible mechanism was also explored. Under the optimal shaking flask conditions, amino acids in mycelium with magnetic field treatment significantly increased, and the morphology of mycelium obviously changed. During the scale-up magnetic field-assisted fermentation, Mycelium biomass increased by 12%. The yield of polysaccharides and relative dissolved oxygen in the fermentation broth was higher than in the control group. Transcriptome sequencing results showed that the expression of genes related to amino acid metabolism increased significantly after magnetic treatment. In addition, magnetic field stimulation enhanced the mycelium biomass by upregulation the expression of genes related to cell repair and stress response. This study suggested that applying a magnetic field in submerged fermentation of G frondosa is an innovative approach to produce metabolites.

Structural characterization of mushroom polysaccharides by cyclic ion mobility-mass spectrometry.

Polysaccharides are biopolymers known to possess various bioactivities. Because of their molecular complexity, the structural characterization of polysaccharides remains challenging, and difficult to be completed with a single analytical method. In this study, a novel approach for the characterization of linkages and anomeric configuration of polysaccharides was proposed. Based on ion mobility-mass spectrometry (IM-MS), a database containing 5 glucotriose standards was set up. Information about the arrival time distribution and fragmentation patterns of these standards were included. The method was validated by three commercially available purified polysaccharides, namely laminarin, dextrin, and dextran, each having distinct connectivity and configuration of the glycosidic bonds. Lastly, the method was successfully applied to analyze polysaccharides prepared from three medicinal mushrooms, namely Xylaria nigripes, Grifola frondosa, and Laetiporus sulphureus. The results showed that water-soluble non-digestible polysaccharides of X. nigripes and G. frondosa were mainly composed of (1→3)-ß-glucan, while that of L. sulphureus was composed of (1→3)-ɑ-glucan. The present method has the advantages of being simple in sample preparation and short analysis time.

Purification and characterization of Se-enriched Grifola frondosa glycoprotein, and evaluating its amelioration effect on As3+ -induced immune toxicity.

BACKGROUND: Selenium (Se)-enriched glycoproteins have been a research highlight for the role of both Se and glycoproteins in immunoregulation. Arsenic (As) is a toxicant that is potentially toxic to the immune function and consequently to human health. Several reports suggested that Se could reduce the toxicity of heavy metals. Moreover, more and more nutrients in food had been applied to relieve As-induced toxicity. Hence glycoproteins were isolated and purified from Se-enriched Grifola frondosa, and their preliminary characteristics as well as amelioration effect and mechanism on As3+ -induced immune toxicity were evaluated. RESULTS: Four factions, namely Se-GPr11 (electrophoresis analysis exhibited one band: 14.32 kDa), Se-GPr22 (two bands: 20.57 and 31.12 kDa), Se-GPr33 (three bands: 15.08, 20.57 and 32.78 kDa) and Se-GPr44 (three bands: 16.73, 32.78 and 42.46 kDa), were obtained from Se-enriched G. frondosa via DEAE-52 and Sephacryl S-400 column. In addition, Se-GPr11 and Se-GPr44 are ideal proteins that contain high amounts of almost all essential amino acids. Thereafter, the RAW264.7 macrophage model was adopted to estimate the effect of Se-GPr11 and Se-GPr44 on As3+ -induced immune toxicity. The results showed that the pre-intervention method was the best consequent and the potential mechanisms were, first, by improving the oxidative stress state (enhancing the activity of superoxide dismutase and glutathione peroxidase, decreasing the levels of reactive oxygen species and malondialdehyde); secondly, through nuclear factor-κB and mitogen-activated protein kinase-mediated upregulation cytokines (interleukin-2 and interferon-γ) secretion induced by As3+ . CONCLUSION: The results suggested Se-enriched G. frondosa may be a feasible supplement to improve health level of the As3+ pollution population. © 2021 Society of Chemical Industry.

Grifola frondosa may play an anti-obesity role by affecting intestinal microbiota to increase the production of short-chain fatty acids.

Background: Grifola frondosa (G. frondosa) is a fungus with good economic exploitation prospects of food and medicine homologation. This study aims to investigate the effects of G. frondosa powder suspension (GFPS) on the intestinal contents microbiota and the indexes related to oxidative stress and energy metabolism in mice, to provide new ideas for developing G. frondosa weight loss products. Methods: Twenty Kunming mice were randomly divided into control (CC), low-dose GFPS (CL), medium-dose GFPS (CM), and high-dose GFPS (CH) groups. The mice in CL, CM, and CH groups were intragastrically administered with 1.425 g/(kg·d), 2.85 g/(kg·d), and 5.735 g/(kg·d) GFPS, respectively. The mice in CC group were given the same dose of sterile water. After 8 weeks, liver and muscle related oxidative stress and energy metabolism indicators were detected, and the intestinal content microbiota of the mice was detected by 16S rRNA high-throughput sequencing. Results: After eight weeks of GFPS intervention, all mice lost weight. Compared with the CC group, lactate dehydrogenase (LDH) and malondialdehyde (MDA) contents in CL, CM, and CH groups were increased, while Succinate dehydrogenase (SDH) and Superoxide Dismutase (SOD) contents in the liver were decreased. The change trends of LDH and SDH in muscle were consistent with those in the liver. Among the above indexes, the change in CH is the most significant. The Chao1, ACE, Shannon, and Simpson index in CL, CM, and CH groups were increased. In the taxonomic composition, after the intervention with GFPS, the short-chain fatty acid (SCFA)-producing bacteria such as unclassified Muribaculaceae, Alloprevotella, and unclassified Lachnospiraceae increased. In linear discriminant analysis effect size (LEfSe) analysis, the characteristic bacteria in CC, CL, CM, and CH groups showed significant differences. In addition, some characteristic bacteria significantly correlated with related energy metabolism indicators. Conclusion: The preventive effect of G. frondosa on obesity is related to changing the structure of intestinal content microbiota and promoting the growth of SCFAs. While excessive intake of G. frondosa may not be conducive to the antioxidant capacity and energy metabolism.

Class I hydrophobin fusion with cellulose binding domain for its soluble expression and facile purification.

Hydrophobins, highly surface-active proteins, have the ability to reverse surface hydrophobicity through self-assembly at the hydrophilic-hydrophobic interfaces. Their unique structure and interfacial activity lead hydrophobins to have potential applications on surface functional modifications. However, class I hydrophobins are prone to self-assemble into highly insoluble amyloid-like rodlets structure. Recombinant hydrophobins could be produced by Escherichia coli but generally as an insoluble inclusion body. To overcome this insoluble expression limitation, cellulose-binding domain (CBD) from Clostridium thermocellum was fused to the N-terminal of class I hydrophobin HGFI to enhance its soluble expression in E. coli. Approximately, 94% of expressed CBD fused HGFI (CBD-HGFI) was found as soluble protein. The fused CBD could also bind specifically onto bacterial cellulose (BC) nanofibrils produced by Komagataeibacter xylinus to facilitate rapid isolation and purification of HGFI from crude extract. Lysostaphin (Lst), known as GlyGly endopeptidase could successfully cleave the flexible linker (GGGGS)2 between CBD and HGFI to recover HGFI from BC-bound CBD-HGFI. CBD-HGFI purified by immobilized metal-chelated affinity chromatography (IMAC) and Lst cleaved BC-CBD-HGFI still retained interfacial activity of hydrophobin and its effect on accelerating PETase hydrolysis against poly(ethylene terephthalate) (PET) fiber.

Antitumor activities of Grifola frondosa (Maitake) polysaccharide: A meta-analysis based on preclinical evidence and quality assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: The antitumor effects of Grifola frondosa/maitake polysaccharide (GFP) have been reported in many preclinical studies, especially in vivo experiments. The present meta-analysis aimed to provide an in vivo evidence and theoretical basis for future clinical trials by assessing the efficacy and underlying mechanisms of GFP in tumor treatment. MATERIALS AND METHODS: English and Chinese databases were examined to include animal experiments to study the antitumor activity of GFP. Literature screening, data extraction, and meta-analysis were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In addition, the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias (RoB) tool was used to assess the risk of bias of the included animal studies. RESULTS: Potentially relevant studies (442) were identified, and finally 24 eligible studies (all in English) were included. The meta-analysis revealed that GFP has significant effects in inhibiting tumor growth (high dose: mean difference (MD) = -1.34, 95% confidence interval (CI) = [-1.73, -0.95]; low dose: MD = -5.68, 95% CI = [-7.27, -4.09]), improving tumor remission rate (odds ratio = 25.59, 95% CI = [9.08, 72.11]), and enhancing immune function in both cellular (CD4+ T cell percentage: MD = 3.03, 95% CI = [1.16, 4.90]; CD8+ T cell percentage: MD = 1.10, 95% CI = [-0.29, 2.49]) and humoral immunity (MD and [95% CI] of interleukin (IL)-2, IL-12 and tumor necrosis factor-α were 7.86 [6.29, 9.44], 35.95 [5.18, 66.72], and 10.03 [8.71, 11.36], respectively), and the differences between the two groups of the above indicators were statistically significant (all P < 0.01) except CD8+ T cell percentage. Additionally, the quality of the included studies was not high, and the risk of bias mainly concentrated on selection, detection, and reporting biases. CONCLUSION: GFP is a potential candidate for tumor treatment and clinical trials. TRIAL REGISTRATION: The review protocol for this study was registered with the PROSPERO database before beginning the review process (CRD42018108897).

The polysaccharides from the Grifola frondosa fruiting body prevent lipopolysaccharide/D-galactosamine-induced acute liver injury via the miR-122-Nrf2/ARE pathways.

Polysaccharides can be used as a potential hepatoprotective agent in the treatment of acute liver injury. However, the underlying mechanism governing how polysaccharides protect against acute liver injury induced by lipopolysaccharide/d-galactosamine (LPS/d-GalN) remains unclear. To investigate the mechanism, the anti-oxidative and anti-inflammatory action and pathways were determined. In this study, we investigated the hepatoprotective effects of Grifola frondosa polysaccharides (GFP), which are obtained from the fruiting body of Grifola frondosa, on (LPS/d-GalN)-induced liver injury in mice. Histopathological analyses showed that GFP protected against LPS/d-GalN-induced lung inflammation. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the levels of the inflammatory mediators tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, and monocyte chemoattractant protein-1 (MCP-1) were inhibited by GFP. The LPS/d-GalN-induced myeloperoxidase (MPO) activity and malondialdehyde (MDA) content were inhibited by GFP. The levels of superoxide dismutase (SOD) and glutathione (GSH) were upregulated by GFP. The GFP-treated group showed reduced expression levels of miR-122 in liver tissue. Nrf2 has been identified as a potential target of miR-122. The western blotting results showed that GFP attenuates LPS/d-GalN-induced acute liver injury via upregulating transcription factors Nrf2, Nqo-1, and HO-1 and downregulating transcription factor Keap-1 in the Nrf2/ARE signaling pathway. In conclusion, these results indicated that GFP was highly effective in inhibiting liver injury and may be a promising potential therapeutic reagent for liver injury treatment. GFP exerts protective effects against LPS/d-GalN-induced liver injury in mice, which may be related to the regulation of the miR-122-Nrf2/ARE pathways.