The impact of continuous cultivation of Ganoderma lucidum on soil nutrients, enzyme activity, and fruiting body metabolites.

To explore the impacts of continuous Ganoderma lucidum cultivation on soil physicochemical factors, soil enzyme activity, and the metabolome of Ganoderma lucidum fruiting bodies, this study conducted two consecutive years of cultivation on the same plot of land. Soil physicochemical factors and enzyme activity were assessed, alongside non-targeted metabolomic analysis of the Ganoderma lucidum fruiting bodies under continuous cultivation. The findings unveiled that in the surface soil layer (0-15 cm), there was a declining trend in organic matter, ammonium nitrogen, available phosphorus, available potassium, pH, polyphenol oxidase, peroxidase, alkaline phosphatase, and sucrase, whereas nitrate nitrogen, electrical conductivity (EC), and salt content exhibited an upward trend. Conversely, in the deeper soil layer (15-30 cm), organic matter, ammonium nitrogen, available potassium, alkaline phosphatase, and sucrase demonstrated a decreasing trend, while nitrate nitrogen, available phosphorus, pH, EC, salt content, polyphenol oxidase, and soil peroxidase showed an increasing trend. Metabolomic analysis of Ganoderma lucidum fruiting bodies distinguished 64 significantly different metabolites between the GCK and GT groups, with 39 components having markedly higher relative contents in GCK and 25 components having significantly lower relative contents in GCK compared to GT. Moreover, among these metabolites, there were more types with higher contents in the fruiting bodies harvested in the first year (GCK) compared to those harvested in the second year (GT), with pronounced differences. KEGG pathway analysis revealed that GCK exhibited more complex metabolic pathways compared to GT. The metabolites of Ganoderma lucidum fruiting bodies were predominantly influenced by soil physicochemical factors and soil enzyme activity. In the surface soil layer (0-15 cm), the metabolome was significantly affected by soil pH, soil organic matter, available phosphorus, and soil alkaline phosphatase, while in the deeper soil layer (15-30 cm), differences in the Ganoderma lucidum metabolome were more influenced by soil alkaline phosphatase, soil catalase, pH, nitrate nitrogen, and soil sucrase.

Time-dependent change in Reishi (Ganoderma lingzhi) triterpenoids in culture with rumen fluid.

The purpose of this study was to investigate the time-dependent change in Reishi (Ganoderma lingzhi) triterpenoids in rumen fluid. G. lingzhi fruiting bodies were milled and incubated in a tube with rumen fluid for 0, 4, 8, 12, 24, and 48 h at 39°C. After incubation, all the tubes were freeze-dried and extracted by ethanol. The contents of 18 triterpenoids in the ethanol extract were quantitated by liquid chromatography-mass spectrometry (LC-MS/MS). Based on the results, triterpenoids were categorized into three groups: (1) rapid decrease, indicating reductions of more than 50% within 8 h; (2) mild decrease, with reductions of more than 50% within 48 h; and (3) minimal change, even after 48 h, there was not much change. Ganoderic acid C6, DM, H, K, and TR as well as Ganoderenic acid D were classified in (1); Ganoderic acid LM2 and T-Q as well as Ganoderiol F in (2); and Ganoderic acid A, B, C1, C2, I, and TN; Gnoderenic acid C; and Ganodermanontriol in (3). In addition, a relationship between chemical structure and metabolic speed was observed in some cases. The results of this study revealed that G. lingzhi triterpenoids are digested and metabolized at different speeds in ruminant fluid.

Strategies to Increase the Production of Triterpene Acids in Ligzhi or Reishi Medicinal Mushroom (Ganoderma lucidum, Agaricomycetes): A Review.

Ganoderic acids (GAs) are the main active ingredient of Ganoderma lucidum, which has been widely accepted as a medicinal mushroom. Due to the low yield of GAs produced by liquid cultured Ganoderma mycelium and solid cultured fruiting bodies, the commercial production and clinical application of GAs are limited. Therefore, it is important to increase the yield of GA in G. lucidum. A comprehensive literature search was performed with no set data range using the following keywords such as "triterpene," "ganoderic acids," "Ganoderma lucidum," and "Lingzhi" within the main databases including Web of Science, PubMed, and China National Knowledge Infrastructure (CNKI). The data were screened using titles and abstracts and those relevant to the topic were included in the paper and was not limited to studies published in English. Present review focuses on the four aspects: fermentation conditions and substrate, extrinsic elicitor, genetic engineering, and mutagenesis, which play significant roles in increasing triterpene acids production, thus providing an available reference for further research on G. lucidum fermentation.

Removal of pharmaceutical compounds and toxicology study in wastewater using Malaysian fungal Ganoderma lucidum.

Elevated usage of pharmaceutical products leads to the accumulation of emerging contaminants in sewage. In the current work, Ganoderma lucidum (GL) was used to remove pharmaceutical compounds (PCs), proposed as a tertiary method in sewage treatment plants (STPs). The PCs consisted of a group of painkillers (ketoprofen, diclofenac, and dexamethasone), psychiatrists (carbamazepine, venlafaxine, and citalopram), beta-blockers (atenolol, metoprolol, and propranolol), and anti-hypertensives (losartan and valsartan). The performance of 800 mL of synthetic water, effluent STP, and hospital wastewater (HWW) was evaluated. Parameters, including treatment time, inoculum volume, and mechanical agitation speed, have been tested. The toxicity of the GL after treatment is being studied based on exposure levels to zebrafish embryos (ZFET) and the morphology of the GL has been observed via Field Emission Scanning Electron Microscopy (FESEM). The findings conclude that GL can reduce PCs from <10% to >90%. Diclofenac and valsartan are the highest (>90%) in the synthetic model, while citalopram and propranolol (>80%) are in the real wastewater. GL effectively removed pollutants in 48 h, 1% of the inoculum volume, and 50 rpm. The ZFET showed GL is non-toxic (LC50 is 209.95 mg/mL). In the morphology observation, pellets GL do not show major differences after treatment, showing potential to be used for a longer treatment time and to be re-useable in the system. GL offers advantages to removing PCs in water due to their non-specific extracellular enzymes that allow for the biodegradation of PCs and indicates a good potential in real-world applications as a favourable alternative treatment.

Structure Identification of Ganoderma lucidum Spore Polysaccharides and Their Antitumor Activity In Vivo.

Ganoderma lucidum spore powder, valued for its nutritional and medicinal properties, contains polysaccharides crucial for its efficacy. However, the complex structural nature of these polysaccharides necessitates further investigation to fully realize their potential. This study aimed to investigate the effects of acid heat treatment on Ganoderma lucidum spore polysaccharides (GLSPs) to enhance their properties and application in antitumor activity. The GLSP was obtained via acid heat treatment, concentration, and centrifugal separation. This process led to a notable reduction in polysaccharide molecular weight, increasing water solubility and bioavailability. Analytical techniques including NMR spectroscopy and methylation analysis revealed a polysaccharide composition comprising four distinct monosaccharides, with molecular weights of 3291 Da (Mw) and 3216 Da (Mn). Six different linkage modes were identified, with a molar ratio of 1:5:2:3:4:3. In vivo experiments demonstrated the GLSP's significant inhibitory effect on the growth of four tumor models (sarcoma S180, Lewis lung cancer, liver cancer H22, and colon cancer C26) in mice, with no observed toxicity. These findings suggest the GLSP's potential as an antitumor therapeutic agent for clinical use.

Ganoderma lucidum Polysaccharide Supplementation Significantly Activates T-Cell-Mediated Antitumor Immunity and Enhances Anti-PD-1 Immunotherapy Efficacy in Colorectal Cancer.

Ganoderma lucidum polysaccharide (GLP) is a prebiotic with immunomodulatory effects. However, the therapeutic potential of GLP in tumor immunotherapy has not been fully explored, especially in T cell-mediated antitumor immunity. In this study, we found that GLP significantly inhibited tumor growth and activated antitumor immunity in colorectal cancer (CRC). In the spleens and tumor tissues, the proportion of cytotoxic CD8+T cells and Th1 helper cells increased, while immunosuppressive Tregs decreased. Additionally, microbiota dysbiosis was alleviated by GLP, and short-chain fatty acid production was increased. Meanwhile, GLP decreased the ratio of kynurenine and tryptophan (Kyn/Trp) in the serum, which contributed to antitumor immunity of T cells. More importantly, the combination of GLP and the immune checkpoint inhibitor anti-PD-1 monoclonal antibody further enhanced the efficacy of anti-PD-1 immunotherapy. Thus, GLP as a prebiotic has the potential to be used in tumor immunotherapy.

Ganoderma lucidum: Multifaceted mechanisms to combat diabetes through polysaccharides and triterpenoids: A comprehensive review.

Diabetes is a chronic metabolic disorder. Diabetes complications can affect many organs and systems in the body. Ganoderma lucidum (G. lucidum) contains various compounds that have been studied for their potential antidiabetic effects, including polysaccharides, triterpenoids (ganoderic acids, ganoderol B), proteoglycans, and G. lucidum extracts. G. lucidum polysaccharides (GLPs) and triterpenoids have been shown to act through distinct mechanisms, such as improving glucose metabolism, modulating the mitogen-activated protein kinase (MAPK) system, inhibiting the nuclear factor-kappa B (NF-κB) pathway, and protecting the pancreatic beta cells. While GLPs exhibit a significant role in controlling diabetic nephropathy and other associated complications. This review states the G. lucidum antidiabetic mechanisms of action and potential biologically active compounds that contribute to diabetes management and associated complications. To make G. lucidum an appropriate replacement for the treatment of diabetes with fewer side effects, more study is required to completely comprehend the number of physiologically active compounds present in it as well as the underlying cellular mechanisms that influence their effects on diabetes.

Temporal dynamics of lignin degradation in Quercus acutissima sawdust during Ganoderma lucidum cultivation.

Despite a fair amount of lignin conversion during mycelial growth, previous structural analyses have not yet revealed how lignin changes continuously and what the relationship is between lignin and ligninolytic enzymes. To clarify these aspects, Quercus acutissima sawdust attaching Ganoderma lucidum mycelium collected from different growth stage was subjected to analysis of lignin structure and ligninolytic enzyme activity. Two key periods of lignin degradation are found during the cultivation of G. lucidum: hypha rapid growth period and primordium formation period. In the first stage, laccase activity is associated with the opening of structures such as methoxyls, ß-O-4' substructures and guaiacyl units in lignin, as well as the shortening of lignin chains. Manganese peroxidases and lignin peroxidases are more suitable for degrading short chain lignin. The structure of phenylcoumarans and syringyl changes greatly in the second stage. The results from sawdust attaching mycelium provide new insights to help improve the cultivation substrate formulation of G. lucidum and understand biomass valorization better.

Ganoderic acid D attenuates gemcitabine resistance of triple-negative breast cancer cells by inhibiting glycolysis via HIF-1α destabilization.

BACKGROUND: Gemcitabine (GEM) resistance is the primary reason why combination chemotherapy is limited in triple-negative breast cancer (TNBC). Ganoderic acid D (GAD), a natural triterpenoid compound obtained from Ganoderma lucidum, has been shown to have antitumor activities. However, whether GAD can reverse GEM resistance in TNBC requires further investigation. PURPOSE: This study investigated whether and how GAD could reverse GEM resistance in TNBC as an antitumor adjuvant. METHODS: The effects of GAD on cell proliferation, cell cycle, and glycolysis were studied in vitro using a GEM-resistant (GEM-R) TNBC cell model. We enriched key pathways affected by GAD using proteomics techniques. Western blotting and qPCR were used to detect the expression of glycolysis-related genes after GAD treatment. A mouse resistance model was established using GEM-R TNBC cells, and hematoxylin-eosin staining and immunohistochemistry were used to assess the role of GAD in reversing resistance in vivo. RESULTS: Cellular functional assays showed that GAD significantly inhibited proliferation and glucose uptake in GEM-R TNBC cells. GAD reduces HIF-1α accumulation in TNBC cells under hypoxic conditions through the ubiquitinated protease degradation pathway. Mechanistically, GAD activates the p53/MDM2 pathway, promoting HIF-1α ubiquitination and proteasomal degradation and downregulating HIF-1α-dependent glycolysis genes like GLUT1, HK2, and PKM2. Notably, GAD combined with gemcitabine significantly reduced the growth of GEM-R TNBC cells in a subcutaneous tumor model. CONCLUSIONS: This study reveals a novel antitumor function of GAD, which inhibits glycolysis by promoting HIF-1α degradation in GEM-R TNBC cells, offering a promising therapeutic strategy for TNBC patients with GEM resistance.

The CBS/H2S signalling pathway regulated by the carbon repressor CreA promotes cellulose utilization in Ganoderma lucidum.

Cellulose is an important abundant renewable resource on Earth, and the microbial cellulose utilization mechanism has attracted extensive attention. Recently, some signalling molecules have been found to regulate cellulose utilization and the discovery of underlying signals has recently attracted extensive attention. In this paper, we found that the hydrogen sulfide (H2S) concentration under cellulose culture condition increased to approximately 2.3-fold compared with that under glucose culture condition in Ganoderma lucidum. Further evidence shown that cellulase activities of G. lucidum were improved by 18.2-27.6% through increasing H2S concentration. Then, we observed that the carbon repressor CreA inhibited H2S biosynthesis in G. lucidum by binding to the promoter of cbs, a key gene for H2S biosynthesis, at "CTGGGG". In our study, we reported for the first time that H2S increased the cellulose utilization in G. lucidum, and analyzed the mechanism of H2S biosynthesis induced by cellulose. This study not only enriches the understanding of the microbial cellulose utilization mechanism but also provides a reference for the analysis of the physiological function of H2S signals.

Structural variety of glucans from Ganoderma lucidum fruiting bodies.

Ganoderma lucidum, widely used in traditional medicine, has several biological properties. Polysaccharides, mainly glucans, are known as one of its main bioactive compounds. Consequently, the achievement and chemical investigation of such molecules are of pharmaceutical interest. Herein, we obtained water-insoluble and water-soluble polysaccharides from G. lucidum by alkaline extraction. Fractionation process yielded three fractions (GLC-1, GLC-2, and GLC-3). All samples showed to be composed mainly of glucans. GLC-1 is a linear (1 â†’ 3)-linked ß-glucan; GLC-2 is a mixture of three different linear polysaccharides: (1 â†’ 3)-ß-glucan, (1 â†’ 3)-α-glucan, and (1 â†’ 4)-α-mannan; while GLC-3 is a branched ß-glucan with a (1 â†’ 4)-linked main chain, which is branched at O-3 or O-6 by (1 â†’ 3)- or (1 â†’ 6)-linked side chains. This research reports the variability of glucans in Ganoderma lucidum fruiting bodies and applicable methodologies to obtain such molecules. These polysaccharides can be further applied in biological studies aiming to investigate how their chemical differences may affect their biological properties.

Polysaccharide structure evaluation of Ganoderma lucidum from different regions in China based on an innovative extraction strategy.

The polysaccharides and triterpenes are important functional components of Ganoderma lucidum, but traditional preparation process of G. lucidum functional components can only realize the preparation of single functional component, which has poor targeting and low efficiency. In this study, the existence state of the functional components of G. lucidum was revealed. Then, the single step extraction process for functional components was established, and the precise structure evaluation of polysaccharide and triterpenes was conducted based on the process. The results showed that preparation time required for this strategy is only one-sixth of the traditional one, and 50 % of raw materials can be saved. Structural analysis of the functional components revealed that triterpenes were mainly Ganoderic acid and Lucidenic acid, and the polysaccharide structure was mainly 1,3-glucan and 1,3,6-glucan. The establishment of single step extraction strategy and the evaluation of the fine structure of functional components improved the efficiency of preparation and result determination, and provided an important basis for the development and utilization of green and low-carbon G. lucidum and even edible fungi resources and human nutritional dietary improvement strategies.

Protective effect of Ganoderma lucidum-fermented crop extracts against hydrogen peroxide- or ß-amyloid-induced damage in human neuronal SH-SY5Y cells.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of stacked ß-amyloid peptides in the brain and associated with the generation of oxidative stress. So far, there is no cure for AD or a way to stop its progression. Although the neuroprotective effects of Ganoderma lucidum aqueous extract and G. lucidum-derived triterpenoids and polysaccharides have been reported, the influence of G. lucidum-fermented crops on AD still lacks clarity. METHODS: This study aimed to investigate the protective effect of G. lucidum-fermented crop extracts against hydrogen peroxide- or ß-amyloid peptide (Aß25-35)-induced damage in human neuroblastoma SH-SY5Y cells. RESULTS: Various extracts of G. lucidum-fermented crops, including extract A: 10% ethanol extraction using microwave, extract B: 70˚C water extraction, and extract C: 100˚C water extraction followed by ethanol precipitation, were prepared and analyzed. Extract B had the highest triterpenoid content. Extract C had the highest total glucan content, while extract A had the highest gamma-aminobutyric acid (GABA) content. The median inhibitory concentration (IC50, mg/g) for DPPH and ABTS scavenging activity of the fermented crop extracts was significantly lower than that of the unfermented extract. Pretreatment with these extracts significantly increased the cell viability of SH-SY5Y cells damaged by H2O2 or Aß25-35, possibly by reducing cellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Moreover, extract B markedly alleviated the activity of acetylcholinesterase (AChE), which is crucial in the pathogenesis of AD. CONCLUSION: These results clearly confirmed the effects of G. lucidum-fermented crop extracts on preventing against H2O2- or Aß25-35-induced neuronal cell death and inhibiting AChE activity, revealing their potential in management of AD.

Sporoderm-broken spores of Ganoderma lucidum modulate hepatoblastoma malignancy by regulating RACK1-mediated autophagy and tumour immunity.

Hepatoblastoma (HB), a primary liver tumour, is notorious for its high metastatic potential and poor prognosis. Ganoderma lucidum, an edible mushroom species utilized in traditional Chinese medicine for addressing various tumour types, presents an intriguing avenue for HB treatment. However, the effectiveness of G. lucidum in managing HB and its underlying molecular mechanism necessitates further exploration. Standard in vitro assays were conducted to evaluate the impact of sporoderm-broken spores of G. lucidum (SBSGL) on the malignant characteristics of HB cells. The mechanism of SBSGL in treating HB and its tumour immunomodulatory effects were explored and validated by various experiments, including immunoprecipitation, Western blotting, mRFP-GFP-LC3 adenovirus transfection and co-localization analysis, as well as verified with in vivo experiments in this regard. The results showed that SBSGL effectively inhibited the malignant traits of HB cells and suppressed the O-GlcNAcylation of RACK1, thereby reducing its expression. In addition, SBSGL inhibited immune checkpoints and regulated cytokines. In conclusion, SBSGL had immunomodulatory effects and regulated the malignancy and autophagy of HB by regulating the O-GlcNAcylation of RACK1. These findings suggest that SBSGL holds promise as a potential anticancer drug for HB treatment.

Synergy of de-walled Ganoderma Lucidum spore powder (GLSP) on targeted therapy in advanced non-squamous non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutant: protocol for a randomized, double-blind, placebo-controlled study.

BACKGROUND: Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant. METHOD/DESIGN: A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.

Minor ergosteroids and a 19-nor labdane-type diterpenoid with anti-inflammatory effects from Ganoderma lucidum.

A chemical investigation on the fruiting bodies of Ganoderma lucidum led to the isolation and identification of five undescribed ergosteroids including two des-D-steroids (3 and 4) and one rare 6/6/7/5-fused carbon skeletal ergosterol (5) along with one 19-nor labdane-type diterpenoid (6). Their structures including their absolute configurations, were assigned by spectroscopic methods, ECD calculations, and X-ray diffraction analysis. In addition, the anti-inflammatory activities of all the isolates were evaluated. The results indicated that compound 1 can significantly down-regulate the protein expression of iNOS and COX-2 at 20 µM in LPS- stimulated RAW264.7 cells.

Identification of sedative-hypnotic compounds shared by five medicinal Polyporales mushrooms using UPLC-Q-TOF-MS/MS-based untargeted metabolomics.

BACKGROUND: Five Polyporales mushrooms, namely Amauroderma rugosum, Ganoderma lucidum, G. resinaceum, G. sinense and Trametes versicolor, are commonly used in China for managing insomnia. However, their active components for this application are not fully understood, restricting their universal recognition. PURPOSE: In this study, we aimed to identify sedative-hypnotic compounds shared by these five Polyporales mushrooms. STUDY DESIGN AND METHODS: A UPLC-Q-TOF-MS/MS-based untargeted metabolomics, including OPLS-DA (orthogonal projection of potential structure discriminant analysis) and OPLS (orthogonal projections to latent structures) analysis together with mouse assays, were used to identify the main sedative-hypnotic compounds shared by the five Polyporales mushrooms. A pentobarbital sodium-induced sleeping model was used to investigate the sedative-hypnotic effects of the five mushrooms and their sedative-hypnotic compounds. RESULTS: Ninety-two shared compounds in the five mushrooms were identified. Mouse assays showed that these mushrooms exerted sedative-hypnotic effects, with different potencies. Six triterpenes [four ganoderic acids (B, C1, F and H) and two ganoderenic acids (A and D)] were found to be the main sedative-hypnotic compounds shared by the five mushrooms. CONCLUSION: We for the first time found that these six triterpenes contribute to the sedative-hypnotic ability of the five mushrooms. Our novel findings provide pharmacological and chemical justifications for the use of the five medicinal mushrooms in managing insomnia.

Ganoderma lucidum-Derived Meroterpenoids Show Anti-Inflammatory Activity In Vitro.

Ganoderma lucidum, known as the "herb of spiritual potency", is used for the treatment and prevention of various diseases, but the responsible constituents for its therapeutic effects are largely unknown. For the purpose of obtaining insight into the chemical and biological profiling of meroterpenoids in G. lucidum, various chromatographic approaches were utilized for the title fungus. As a result, six undescribed meroterpenoids, chizhienes A-F (1-6), containing two pairs of enantiomers (4 and 5), were isolated. Their structures were identified using spectroscopic and computational methods. In addition, the anti-inflammatory activities of all the isolates were evaluated by Western blot analysis in LPS-induced macrophage cells (RAW264.7), showing that 1 and 3 could dose dependently inhibit iNOS but not COX-2 expression. Further, 1 and 3 were found to inhibit nitric oxide (NO) production using the Greiss reagent test. The current study will aid in enriching the structural and biological diversity of Ganoderma-derived meroterpenoids.

Structural characterization of a galactoglucomannan with anti-neuroinflammatory activity from Ganoderma lucidum.

According to traditional Chinese medicine theory, Ganoderma lucidum (G. lucidum) presents certain effects for nourishing nerves and calming the mind. G. lucidum polysaccharides (GLPs) have various biological activities; however, the structural characterization and the structure-activity relationship in anti-neuroinflammation of GLPs needs to be further investigated. In this work, the crude polysaccharide GL70 exhibited a remarkable impact on enhancing the spatial learning and memory function, as well as reducing the anxiety symptoms of the lipopolysaccharide (LPS)-induced rat model of Alzheimer's disease (AD). A galactoglucomannan (GLP70-1-2) was isolated from GL70, and characterized by monosaccharide composition, partial acid hydrolysis, methylation, and NMR analysis. The backbone of GLP70-1-2 was →6)-α-D-glcp-(1 â†’ 6)-ß-D-galp-(1 â†’ [6)-ß-D-manp-(1]3 â†’ 4)-α-D-Glcp-(1 â†’ 6)-α-D-glcp-(1 â†’ 2)-ß-D-galp-(1 â†’ [4)-α-D-glcp-(1 â†’ 6)-ß-D-manp-(1 â†’ 2)-ß-D-galp-(1]2 â†’ 6)-ß-D-glcp-(1 â†’ 6)-ß-D-glcp-(1→ with two side chains attached to O-4 of →6)-ß-D-galp-(1→ and O-3 of →6)-ß-D-glcp-(1→, respectively. In addition, GLP70-1-2 exhibited remarkable efficacy in decreasing the level of pro-inflammatory factors in LPS-activated BV2 cells through the TLR4/MyD88/NF-κB pathway. Collectively, GLP70-1-2 exhibited significant anti-neuroinflammatory activity and may have the potential for developing as a drug for AD.

Glsirt1-mediated deacetylation of GlCAT regulates intracellular ROS levels, affecting ganoderic acid biosynthesis in Ganoderma lucidum.

Lysine acetylation is a reversible, dynamic protein modification regulated by lysine acetyltransferases and deacetylases. However, in Basidiomycetes, the extent of lysine acetylation of nonhistone proteins remains largely unknown. Recently, we identified the deacetylase Glsirt1 as a key regulator of the biosynthesis of ganoderic acid (GA), a key secondary metabolite of Ganoderma lucidum. To gain insight into the characteristics, extent, and biological function of Glsirt1-mediated lysine acetylation in G. lucidum, we aimed to identify additional Glsirt1 substrates via comparison of acetylomes between wild-type (WT) and Glsirt1-silenced mutants. A large amount of Glsirt1-dependent lysine acetylation occurs in G. lucidum according to the results of this omics analysis, involving energy metabolism, protein synthesis, the stress response and other pathways. Our results suggest that GlCAT is a direct target of Glsirt1 and that the deacetylation of GlCAT by Glsirt1 reduces catalase activity, thereby leading to the accumulation of intracellular reactive oxygen species (ROS) and positively regulating the biosynthesis of GA. Our findings provide evidence for the involvement of nonhistone lysine acetylation in the biological processes of G. lucidum and help elucidate the involvement of important ROS signaling molecules in regulating physiological and biochemical processes in this organism. In conclusion, this proteomic analysis reveals a striking breadth of cellular processes affected by lysine acetylation and provides new nodes of intervention in the biosynthesis of secondary metabolites in G. lucidum.