Uncovering anti-influenza mechanism of Ophiocordyceps sinensis using network pharmacology, molecular pharmacology, and metabolomics.

Ophiocordyceps sinensis is a precious Chinese traditional herb with a long medicinal history. This study used UPLC-MS metabolomics to explore and compare the metabolic profiles of the stroma (OSBSz), sclerotium (OSBSh), and mycelium (OSBS) of O sinensis to analyze their differential metabolites and identified potential active components. Then combined with network pharmacology and molecular docking to explore the mechanism of differential metabolites with anti-influenza properties. The results indicate that the stroma, sclerotium, and mycelium showed significant differences in metabolites. The key pathways for differential metabolites were butanoate metabolism, thiamin metabolism, alanine, aspartate and glutamate metabolism, citrate cycle, and arginine biosynthesis. Protein-protein interaction analysis identified potential targets, including SRC, RHOA, HSP90AA1, VEGFA, ITGB1, PRKCA, and ITGA1, and the key protective pathways in-volved PI3K-Akt, HIF-1, influenza A, and Coronavirus disease 2019. The molecular docking results showed that the core metabolite D-(-)-glutamine has high binding affinity with SRC, RHOA, and EGFR, re-flecting the multi-component and multi-target network system of O sinensis. In short, the combination of metabonomics, network pharmacology and macromolecular docking technology provides a new way to explore the anti-influenza research of O sinensis. This is undoubtedly an important theoretical support for the clinical application of O sinensis in the future.

The mechanism of action of Ophiocordyceps sinensis mycelia for prevention of acute lung injury based on non-targeted serum metabolomics.

Ophiocordyceps sinensis is a fungus with medicinal value in treating lung diseases, but no study has reported how to prevent acute lung injury using this fungus. The mice were divided into normal, model, positive control, and O. sinensis groups to observe lung histopathological sections and transmission electron microscopy, along with liquid chromatography-mass spectrometry and hematoxylin and eosin (H&E) staining to closely identify structural differences resulting from destruction between the groups. The results of the H&E staining showed that, compared with the normal group, the model group showed alveolar collapse. Compared with the model group, the infiltration of inflammatory cells in the alveolar cavity of the O. sinensis group was significantly reduced. Mitochondrial plate-like cristae were observed in type II alveolar cells of the normal group, with normal coloration of the mitochondrial matrix. Type II alveolar cells in the model group showed obvious edema. The statuses of type II alveolar cells in the O. sinensis and positive groups were similar to that in the normal group. Twenty-nine biomarkers and 10 related metabolic pathways were identified by serum metabolomics screening. The results showed that O. sinensis mycelia had a significant effect on the prevention of lipopolysaccharide-induced inflammation.

Effect of Abiotic Factors on Fumosorinone Production from Cordyceps fumosorosea via Solid-State Fermentation.

Cordyceps fumosorosea is an important species in the genus of Cordyceps, containing a variety of bioactive compounds, including fumosorinone (FU). This study was a ground-breaking assessment of FU levels in liquid and solid cultures. The present study focused on the impacts of solid-state fermentation (SSF) using solid substrates (wheat, oat, and rice), as well as the effects of fermentation parameters (pH, temperature, and incubation period), on the generation of FU. All the fermentation parameters had significant effects on the synthesis of FU. In a study of 25 °C, 5.5 pH, and 21 days of incubation period combinations calculated -to give maximal FU production, it was found that the optimal values were 25 °C, 5.5 pH, and 21 days, respectively. In a solid substrate medium culture, FU could be produced from SSF. At 30 days, a medium composed of rice yielded the most FU (798.50 mg/L), followed by a medium composed of wheat and oats (640.50 and 450.50 mg/L), respectively. An efficient method for increasing FU production on a large scale could be found in this approach. The results of this study might have multiple applications in different industrial fermentation processes.

Integrated Omics Approach to Discover Differences in the Metabolism of a New Tibetan Desmodesmus sp. in Two Types of Sewage Treatments.

Microalgae are now widely applied in municipal (YH_3) and industrial sewage (YH_4) treatments. Through integrated omics analysis, we studied the similarities and differences at the molecular level between the two different types of sewage treatment processes. The most significantly enriched gene ontology (GO) terms in both types of sewage treatments were the ribosome, photosynthesis, and proteasome pathways. The results show that the pathways of differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were enriched for photosynthesis, glyoxylate and dicarboxylate metabolism, and carbon fixation in photosynthetic organisms. Considering YH_3 vs. YH_4, the metabolism of citrate, sedoheptulose-7P, and succinate was significantly upregulated. In addition, the results showed that the pathways of DEGs and DAMs were enriched in terms of amino acid metabolism and carotenoid biosynthesis in YH_4 vs. YH_3. The metabolism of S-Adenosyl-L-homocysteine was significantly downregulated, 2-oxobutanoate was significantly upregulated and downregulated, and the metabolism of abscisic acid glucose ester (ABA-GE) was also significantly upregulated. Overall, the results of this paper will help to improve the basic knowledge of the molecular response of microalgae to sewage treatments, and help design a response strategy based on microalgae for complex, mixed sewage treatments.

A new Desmodesmus sp. from the Tibetan Yamdrok Lake.

Revegetation of exposed sub-soil, while a desirable recovery strategy, often fails due to extreme soil chemical properties, such as low organic matter and pH levels. Microalgae play a key role in maintaining water quality in the lakes and rivers on the Qinghai-Tibet plateau. Plateau microalgae have extensive application prospects in environmental purification, biotechnology, medicine and cosmetics, food industry, and renewable energy. To identify the high biomass of microalgae present in nature, microalgae with the greatest biomass were screened from natural water samples through filtration, pre-culture, and plate scribing separation. Following identification via 18S rRNA sequencing as for the Desmodesmus sp., we constructed a neighbor-joining phylogenetic tree. The novel Desmodesmus sp. from the Tibetan Yamdrok Lake were identified through polyphasic taxonomy. Simultaneously, the sequence of the experimental samples and the target species were shown different following the identification and analysis of SNP and InDel loci. The light-absorbing properties of plateau Desmodesmus sp. have been investigated previously. The characteristic absorption peak of Desmodesmus sp. on the plateau was measured at 689 nm in the visible spectrum using full wavelength scanning with a UV-Vis spectrophotometer. For Desmodesmus sp. which is prone to settling in the process of amplification culture. By monitoring the change trend of total nitrogen, total phosphorus, pH and electrical conductivity in algae solution system, we determined that the logarithmic growth phase and the best transfer window of Desmodesmus sp. were at 15-20 days. This study can provide basic research methods for the study of microalgae in high altitude areas, and lay a foundation for the later study and application of microalgae.

Comparison of Widely Targeted Metabolomics and Untargeted Metabolomics of Wild Ophiocordyceps sinensis.

The authors of this paper conducted a comparative metabolomic analysis of Ophiocordyceps sinensis (OS), providing the metabolic profiles of the stroma (OSBSz) and sclerotia (OSBSh) of OS by widely targeted metabolomics and untargeted metabolomics. The results showed that 778 and 1449 metabolites were identified by the widely targeted metabolomics and untargeted metabolomics approaches, respectively. The metabolites in OSBSz and OSBSh are significantly differentiated; 71 and 96 differentially expressed metabolites were identified by the widely targeted metabolomics and untargeted metabolomics approaches, respectively. This suggests that these 71 metabolites (riboflavine, tripdiolide, bromocriptine, lumichrome, tetrahymanol, citrostadienol, etc.) and 96 metabolites (sancycline, vignatic acid B, pirbuterol, rubrophen, epalrestat, etc.) are potential biomarkers. 4-Hydroxybenzaldehyde, arginine, and lumichrome were common differentially expressed metabolites. Using the widely targeted metabolomics approach, the key pathways identified that are involved in creating the differentiation between OSBSz and OSBSh may be nicotinate and nicotinamide metabolism, thiamine metabolism, riboflavin metabolism, glycine, serine, and threonine metabolism, and arginine biosynthesis. The differentially expressed metabolites identified using the untargeted metabolomics approach were mainly involved in arginine biosynthesis, terpenoid backbone biosynthesis, porphyrin and chlorophyll metabolism, and cysteine and methionine metabolism. The purpose of this research was to provide support for the assessment of the differences between the stroma and sclerotia, to furnish a material basis for the evaluation of the physical effects of OS, and to provide a reference for the selection of detection methods for the metabolomics of OS.