Cordycepin: A Biotherapeutic Molecule from Medicinal Mushroom
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ABSTRACT:
SUBMITTER: Singh B
PROVIDER: S-EPMC7123108 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
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Project description:Age-related male sexual dysfunction covers a wide variety of issues, together with spermatogenic and testicular impairment. In the present work, the effects of cordycepin (COR), an active constituent of a nutrient powerhouse Cordyceps militaris Linn, on senile testicular dysfunction in rats was investigated. The sperm kinematics, antioxidant enzymes, spermatogenic factors, sex hormone receptors, histone deacetylating sirtuin 1 (SIRT1), and autophagy-related mammalian target of rapamycin complex 1 (mTORC1) expression in aged rat testes were evaluated. Sprague Dawley rats were divided into young control (2-month-old; YC), aged control (12-month-old; AC), and aged plus COR-treated groups (5 (COR-5), 10 (COR-10), and 20 (COR-20) mg/kg). The AC group showed reduced sperm kinematics and altered testicular histomorphology compared with the YC group (p < 0.05). However, compared with the AC group, the COR-treated group exhibited improved sperm motility, progressiveness, and average path/straight line velocity (p < 0.05-0.01). Alterations in spermatogenesis-related protein and mRNA expression were significantly ameliorated (p < 0.05) in the COR-20 group compared with the AC group. The altered histone deacetylating SIRT1 and autophagy-related mTORC1 molecular expression in aged rats were restored in the COR-20 group (p < 0.05). In conclusion, the results suggest that COR holds immense nutritional potential and therapeutic value in ameliorating age-related male sexual dysfunctions.
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Project description:Ganoderma lucidum is a widely used medicinal macrofungus in traditional Chinese medicine that creates a diverse set of bioactive compounds. Here we report its 43.3-Mb genome, encoding 16,113 predicted genes, obtained using next-generation sequencing and optical mapping approaches. The sequence analysis reveals an impressive array of genes encoding cytochrome P450s (CYPs), transporters and regulatory proteins that cooperate in secondary metabolism. The genome also encodes one of the richest sets of wood degradation enzymes among all of the sequenced basidiomycetes. In all, 24 physical CYP gene clusters are identified. Moreover, 78 CYP genes are coexpressed with lanosterol synthase, and 16 of these show high similarity to fungal CYPs that specifically hydroxylate testosterone, suggesting their possible roles in triterpenoid biosynthesis. The elucidation of the G. lucidum genome makes this organism a potential model system for the study of secondary metabolic pathways and their regulation in medicinal fungi.
| S-EPMC3621433 | biostudies-literature
Project description:Ganoderma lucidum is one of the well-known medicinal basidiomycetes worldwide. The mitochondrion, referred to as the second genome, is an organelle found in most eukaryotic cells and participates in critical cellular functions. Elucidating the structure and function of this genome is important to understand completely the genetic contents of G. lucidum. In this study, we assembled the mitochondrial genome of G. lucidum and analyzed the differential expressions of its encoded genes across three developmental stages. The mitochondrial genome is a typical circular DNA molecule of 60,630 bp with a GC content of 26.67%. Genome annotation identified genes that encode 15 conserved proteins, 27 tRNAs, small and large rRNAs, four homing endonucleases, and two hypothetical proteins. Except for genes encoding trnW and two hypothetical proteins, all genes were located on the positive strand. For the repeat structure analysis, eight forward, two inverted, and three tandem repeats were detected. A pair of fragments with a total length around 5.5 kb was found in both the nuclear and mitochondrial genomes, which suggests the possible transfer of DNA sequences between two genomes. RNA-Seq data for samples derived from three stages, namely, mycelia, primordia, and fruiting bodies, were mapped to the mitochondrial genome and qualified. The protein-coding genes were expressed higher in mycelia or primordial stages compared with those in the fruiting bodies. The rRNA abundances were significantly higher in all three stages. Two regions were transcribed but did not contain any identified protein or tRNA genes. Furthermore, three RNA-editing sites were detected. Genome synteny analysis showed that significant genome rearrangements occurred in the mitochondrial genomes. This study provides valuable information on the gene contents of the mitochondrial genome and their differential expressions at various developmental stages of G. lucidum. The results contribute to the understanding of the functions and evolution of fungal mitochondrial DNA.
| S-EPMC3753355 | biostudies-literature
Project description:The beneficial effects of edible mushrooms for improving chronic intractable diseases have been documented. However, the antiatherogenic activity of the new medicinal mushroom Grifola gargal is unknown. Therefore, we evaluated whether Grifola gargal can prevent or delay the progression of atherosclerosis. Atherosclerosis was induced in ApoE lipoprotein-deficient mice by subcutaneous infusion of angiotensin II. Grifola gargal extract (GGE) was prepared and intraperitoneally injected. The weight of heart and vessels, dilatation/atheroma formation of thoracic and abdominal aorta, the percentage of peripheral granulocytes, and the blood concentration of MCP-1/CCL2 were significantly reduced in mice treated with GGE compared to untreated mice. By contrast, the percentage of regulatory T cells and the plasma concentration of SDF-1/CXCL12 were significantly increased in mice treated with the mushroom extract compared to untreated mice. In vitro, GGE significantly increased the secretion of SDF-1/CXCL12, VEGF, and TGF-β1 from fibroblasts compared to control. This study demonstrated for the first time that Grifola gargal therapy can enhance regulatory T cells and ameliorate atherosclerosis in mice.
| S-EPMC4523071 | biostudies-literature
Project description:RNA editing is a widespread, post-transcriptional molecular phenomenon that diversifies hereditary information across various organisms. However, little is known about genome-scale RNA editing in fungi. In this study, we screened for fungal RNA editing sites at the genomic level in Ganoderma lucidum, a valuable medicinal fungus. On the basis of our pipeline that predicted the editing sites from genomic and transcriptomic data, a total of 8906 possible RNA-editing sites were identified within the G. lucidum genome, including the exon and intron sequences and the 5'-/3'-untranslated regions of 2991 genes and the intergenic regions. The major editing types included C-to-U, A-to-G, G-to-A, and U-to-C conversions. Four putative RNA-editing enzymes were identified, including three adenosine deaminases acting on transfer RNA and a deoxycytidylate deaminase. The genes containing RNA-editing sites were functionally classified by the Kyoto Encyclopedia of Genes and Genomes enrichment and gene ontology analysis. The key functional groupings enriched for RNA-editing sites included laccase genes involved in lignin degradation, key enzymes involved in triterpenoid biosynthesis, and transcription factors. A total of 97 putative editing sites were randomly selected and validated by using PCR and Sanger sequencing. We presented an accurate and large-scale identification of RNA-editing events in G. lucidum, providing global and quantitative cataloging of RNA editing in the fungal genome. This study will shed light on the role of transcriptional plasticity in the growth and development of G. lucidum, as well as its adaptation to the environment and the regulation of valuable secondary metabolite pathways.
| S-EPMC3982681 | biostudies-literature
Project description:Cordyceps militaris is a well-known edible medicinal mushroom in East Asia that contains abundant and diverse bioactive compounds. Since traditional genome editing systems in C. militaris were inefficient and complicated, here, we show that the codon-optimized cas9, which was used with the newly reported promoter Pcmlsm3 and terminator Tcmura3, was expressed. Furthermore, with the help of the negative selection marker ura3, a CRISPR-Cas9 system that included the Cas9 DNA endonuclease, RNA presynthesized in vitro and a single-strand DNA template efficiently generated site-specific deletion and insertion. This is the first report of a CRISPR-Cas9 system in C. militaris, and it could accelerate the genome reconstruction of C. militaris to meet the need for rapid development in the fungi industry.
| S-EPMC6005869 | biostudies-literature
Project description:Context. Pleurotus ostreatus (P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. Objectives:The present study investigates the anti-inflammatory potential of P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. Materials and Methods. Anti-inflammatory activity was evaluated using suspensions of freeze-dried and powdered (SFDP) P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. in vivo and in vitro assays. Results:At doses of 500-1000?mg/kg, the SFDP of P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. in vitro assays. P < 0.05). Dose-dependent inhibition of NO production was seen with in vitro assays. P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae. r?=?0.95; P < 0.05). Dose-dependent inhibition of NO production was seen with Discussion and Conclusion. The promising activity of culinary mushroom P.o against inflammation suggests its potential application as a functional food during inflammatory conditions.P.o) is a culinary mushroom which is commonly called as "oyster mushroom" belonging to the Basidiomycetous fungi of the order Agaricales and family Pleurotaceae.
| S-EPMC7077046 | biostudies-literature
Project description:BACKGROUND:Genome mining facilitated by heterologous systems is an emerging approach to access the chemical diversity encoded in basidiomycete genomes. In this study, three sesquiterpene synthase genes, GME3634, GME3638, and GME9210, which were highly expressed in the sclerotium of the medicinal mushroom Lignosus rhinocerotis, were cloned and heterologously expressed in a yeast system. RESULTS:Metabolite profile analysis of the yeast culture extracts by GC-MS showed the production of several sesquiterpene alcohols (C15H26O), including cadinols and germacrene D-4-ol as major products. Other detected sesquiterpenes include selina-6-en-4-ol, ?-elemene, ?-cubebene, and cedrene. Two purified major compounds namely (+)-torreyol and ?-cadinol synthesised by GME3638 and GME3634 respectively, are stereoisomers and their chemical structures were confirmed by 1H and 13C NMR. Phylogenetic analysis revealed that GME3638 and GME3634 are a pair of orthologues, and are grouped together with terpene synthases that synthesise cadinenes and related sesquiterpenes. (+)-Torreyol and ?-cadinol were tested against a panel of human cancer cell lines and the latter was found to exhibit selective potent cytotoxicity in breast adenocarcinoma cells (MCF7) with IC50 value of 3.5 ± 0.58 ?g/ml while ?-cadinol is less active (IC50 = 18.0 ± 3.27 ?g/ml). CONCLUSIONS:This demonstrates that yeast-based genome mining, guided by transcriptomics, is a promising approach for uncovering bioactive compounds from medicinal mushrooms.
| S-EPMC5468996 | biostudies-literature
Project description:BACKGROUND:Ganoderma lucidum, one of the best-known medicinal mushrooms in the world, produces more than 400 different bioactive compounds. However, the regulation of these bioactive compounds biosynthesis is still unclear. Lysine succinylation is a critical post-translational modification and has many important functions in all aspects of eukaryotic and prokaryotic cells. Although it has been studied for a long time, its function is still unclear in G. lucidum. In this study, a global investigation was carried out on the succinylome in G. lucidum. RESULTS:In total, 382 modified proteins which contain 742 lysine succinylated sites were obtained. The proteomics data are available through ProteomeXchange with the dataset accession number PXD013954. Bioinformatics analysis revealed that the succinylated proteins were distributed in various cellular biological processes and participated in a great variety of metabolic pathways including carbon metabolism and biosynthesis of secondary metabolites. Notably, a total of 47 enzymes associated with biosynthesis of triterpenoids and polysaccharides were found to be succinylated. Furthermore, two succinylated sites K90 and K106 were found in the conserved Fve region of immunomodulatory protein LZ8. These observations show that lysine succinylation plays an indispensable role in metabolic regulation of bioactive compounds in G. lucidum. CONCLUSIONS:These findings indicate that lysine succinylation is related to many metabolic pathways, especially pharmacologically bioactive compounds metabolism. This study provides the first global investigation of lysine succinylation in G. lucidum and the succinylome dataset provided in this study serves as a resource to further explore the physiological roles of these modifications in secondary metabolism.
| S-EPMC6636155 | biostudies-literature
Project description:In the search for novel anti-infectives from natural sources, fungi, in particular basidiomycetes, have proven to still harbor so much potential in terms of secondary metabolites diversity. There have been numerous reports on isolating numerous secondary metabolites from genus Laetiporus. This study reports on two new triterpenoids, laetiporins C and D, and four known triterpenes from the fruiting body of L. sulphureus. The structures of the isolated compounds were elucidated based on their 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data in combination with high-resolution electrospray mass spectrometric (HR-ESIMS) data. Laetiporin C exhibited weak antifungal activity against Mucor hiemalis. Furthermore, the compounds showed weak antiproliferative activity against the mouse fibroblast L929 and human cancer cell lines, including KB-3-1, A431, MCF-7, PC-3 and A549.
| S-EPMC8658958 | biostudies-literature