The mushroom, Sanghuang is widely used in Asian countries. This medicinal fungus produces diverse bioactive compounds and possesses a potent ability to degrade the wood of the mulberry tree. However, the genes, pathways, and mechanisms that are involved in the biosynthesis of the active compounds and wood degradation by Sanghuang mushroom are still unknown. Here, we report a 34.5 Mb genome—encoding 11,310 predicted genes—of this mushroom. About 16.88% (1909) of the predicted genes have been successfully classified as EuKaryotic Orthologous Groups, and approximately 27.23% (665) of these genes are involved in metabolism. Additionally, a total of 334 genes encoding CAZymes—and their characteristics—were compared with those of the other fungi. Homologous genes involved in triterpenoid, polysaccharide, and flavonoid biosynthesis were identified, and their expression was examined during four developmental stages, 10 and 20 days old mycelia, 1 year old and 3 years old fruiting bodies. Importantly, the lack of chalcone isomerase 1 in the flavonoid biosynthesis pathway suggested that different mechanisms were used in this mushroom to synthesize flavonoids than those used in plants. In addition, 343 transporters and 4 velvet family proteins, involved in regulation, uptake, and redistribution of secondary metabolites, were identified. Genomic analysis of this fungus provides insights into its diverse secondary metabolites, which would be beneficial for the investigation of the medical applications of these pharmacological compounds in the future.

Ultrasonic-microwave assisted extraction (UMAE) of Trametes orientalis polysaccharides was optimized by response surface methodology. Hepatoprotective effects of a purified T. orientalis polysaccharide (TOP-2) were evaluated by alcohol-induced liver injury model mice. The optimal UMAE parameters were indicated as below: ratio of water to raw material 28 mL/g, microwave power 114 W, extraction time 11 min. The polysaccharides yield was 7.52 ± 0.12%, which was well consistent with the predicted value of 7.54%. Pre-treatment with TOP-2 effectively increased the liver index and spleen index in alcohol-treated mice. The elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of mice after alcohol exposure were inhibited by TOP-2 administration. The liver tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels have decreased significantly as a result of alcohol exposure, while pre-treatment with TOP-2 could mitigate these consequences. Furthermore, pre-treatment with TOP-2 could efficiently boost the superoxidase dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, and observably constrain the malondialdehyde (MDA) level. The findings suggest that TOP-2 might be useful for alleviating the alcohol-induced hepatotoxicity via its antioxidant and anti-inflammatory potential.

This study investigated the purification, preliminary structure and in vivo immunomodulatory activities of polysaccharides from the spores of Cordyceps cicadae (CCSP). The crude CCSP was purified by diethylaminoethyl (DEAE)-cellulose and Sephadex G-100 chromatography, affording CCSP-1, CCSP-2 and CCSP-3 with molecular weights of 1.79 × 10⁶, 5.74 × 10⁴ and 7.93 × 10³ Da, respectively. CCSP-2 consisted of mannose and glucose, while CCSP-1 and CCSP-3 are composed of three and four monosaccharides with different molar ratios, respectively. CCSP-2 exhibited its ameliorative effects in cyclophosphamide-induced immunosuppressed mice through significantly increasing spleen and thymus indices, enhancing macrophage phagocytic activity, stimulating splenocyte proliferation, improving natural killer (NK) cytotoxicity, improving bone marrow suppression, regulating the secretion of cytokines and immunoglobulins, and modulating antioxidant enzyme system. These results indicate that CCSP-2 might be exploited as a promising natural immunomodulator.

Cordyceps militaris readily performs sexual reproduction, thus providing a remarkably rich model for understanding the processes involved in sexual development. It could regulate expression of human genes by diet-derived miRNA-like RNAs (milRNAs). However, the study of miRNAs in C. militaris has been limited. In the present study, genes encoding Dicers, Argonautes, and RNA-dependent RNA polymerases were identified. Illumina deep sequencing was performed to characterize the milRNAs in C. militaris at asexual and sexual development stages. Total 38 milRNAs were identified and five milRNAs were validated by northern blot and qRT-PCR, out of which, 19 were specific for sexual development. Importantly, the fungi could not form fruiting bodies after disruption of milR4, while the perithecium was formed in advance after over-expression of milR4. Abnormal pale yellow fruiting body primordium, covered with abnormal primordium, was formed in the strain with miR16 disruption. Although no milR4 or milR16 target genes were identified, differential expression of many different genes involved in mycelium growth and sexual development (mating process, mating signaling, and fruiting body development) among these mutants were found. Overall, milRNAs play vital roles in sexual development in C. militaris.

Introduction: The polysaccharides found in Cordyceps cicadae (C. cicadae) have received increasing academic attention owing to their wide variety of therapeutic activities.Methods: This study evaluated the hypoglycemic, antioxidant, and anti-inflammatory effects of polysaccharides from C. cicadae (CH-P). In addition, 16s rDNA sequencing and untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) were used to estimate the changes and regulatory relationships between gut microbiota and its metabolites. The fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling.Results: The results showed that CH-P treatment displayed hypoglycemic, antioxidant, and anti-inflammatory effects and alleviated tissue damage induced by diabetes. The CH-P treatment significantly reduced the Firmicutes/Bacteroidetes ratio and increased the abundance of Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, Mucispirillum, and significantly decreased the abundance of Helicobacter and Lactobacillus compared to the diabetic group. The alterations in the metabolic pathways were mostly related to amino acid biosynthesis and metabolic pathways (particularly those involving tryptophan) according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Correlation analysis showed that Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, and Mucispirillum were positively correlated with indole and its derivatives, such as 5-hydroxyindole-3-acetic acid. Indole intervention significantly improved hyperglycemic symptoms and insulin sensitivity, and increased the secretion of glucagon-like peptide-1 (GLP-1) in diabetic mice. FMT reduced blood glucose levels, improved glucose tolerance, and increased insulin sensitivity in diabetic mice. However, FMT did not significantly improve GLP-1 levels.Discussion: This indicates that C. cicadae polysaccharides alleviate hyperglycemia by regulating the production of metabolites other than indole and its derivatives by gut microbiota. This study provides an important reference for the development of novel natural products.

Gut microbiota dysbiosis has been reported as a risk factor in the development of type 2 diabetes mellitus (T2DM). Polysaccharides from Phellinus igniarius (P. igniarius) possess various properties that help manage metabolic diseases; however, their underlying mechanism of action remains unclear. Therefore, in this study, we aimed to evaluate the effect of P. igniarius polysaccharides (SH-P) on improving hyperglycemia in mice with T2DM and clarified its association with the modulation of gut microbiota and their metabolites using 16S rDNA sequencing and liquid chromatography–mass spectrometry. Fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling. SH-P supplementation alleviated hyperglycemia symptoms in T2DM mice, ameliorated gut dysbiosis, and significantly increased the abundance of Lactobacillus in the gut. Pathway enrichment analysis indicated that SH-P treatment altered metabolic pathways associated with the occurrence and development of diabetes. Spearman’s correlation analysis revealed that changes in the dominant bacterial genera were significantly correlated with metabolite levels closely associated with hyperglycemia. Additionally, FMT significantly improved insulin sensitivity and antioxidative capacity and reduced inflammation and tissue injuries, indicating improved glucose homeostasis. These results indicate that the ameliorative effects of SH-P on hyperglycemia are associated with the modulation of gut microbiota composition and its metabolites.