In this paper, a method for rapid detection of cordycepin in food was established based on surface-enhanced Raman spectroscopic analysis method. The surface-enhanced Raman substrates were screened ...and the Raman detection conditions and sample pretreatment methods were optimized. The optimal substrate was gold nanocolloid, and the optimal detection conditions were as follows: the addition amount of gold nanocolloid was 200 μL of gold nanocolloid and the sample addition amount was 5 μL. Under the optimal conditions, the detection limit of cordycepin was 1 mg/L, and the sample pretreatment was performed by methanol extraction. Based on the established surface-enhanced Raman spectroscopy (SERS) method, cordycepin in two Cordyceps militaris was detected, which confirmed the practical application of this method.
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•High doses of cordycepin are lethal to G. mellonella.•Cordycepin interacts with EPF to increase the rate of G. mellonella mortality.•Cordycepin reduces immune-related gene expression ...in G. mellonella and S2r+ cells.
Hypocrealean entomopathogenic fungi (EPF) (Sordariomycetes, Ascomycota) are natural regulators of insect populations in terrestrial environments. Their obligately-killing life-cycle means that there is likely to be strong selection pressure for traits that allow them to evade the effects of the host immune system. In this study, we quantified the effects of cordycepin (3′-deoxyadenosine), a secondary metabolite produced by Cordyceps militaris (Hypocreales, Cordycipitaceae), on insect susceptibility to EPF infection and on insect immune gene expression. Application of the immune stimulant curdlan (20 µg ml−1, linear beta-1,3-glucan, a constituent of fungal cell walls) to Drosophila melanogaster S2r+ cells resulted in a significant increase in the expression of the immune effector gene metchnikowin compared to a DMSO-only control, but there was no significant increase when curdlan was co-applied with 25 µg ml−1 cordycepin dissolved in DMSO. Injection of cordycepin into larvae of Galleria mellonella (Lepidoptera: Pyralidae) resulted in dose-dependent mortality (LC50 of cordycepin = 2.1 mg per insect 6 days after treatment). Incubating conidia of C. militaris and Beauveria bassiana (Hypocreales, Cordycipitaceae; an EPF that does not synthesize cordycepin) with 3.0 mg ml−1 cordycepin had no effect on the numbers of conidia germinating in vitro. Co-injection of G. mellonella with a low concentration of cordycepin (3.0 mg ml−1) plus 10 or 100 conidia per insect of C. militaris or B. bassiana caused a significant decrease in insect median survival time compared to injection with the EPF on their own. Analysis of predicted vs. observed mortalities indicated a synergistic interaction between cordycepin and the EPF. The injection of C. militaris and B. bassiana into G. mellonella resulted in increased expression of the insect immune effector genes lysozyme, IMPI and gallerimycin at 72 h post injection, but this did not occur when the EPF were co-injected with 3.0 mg ml−1 cordycepin. In addition, we observed increased expression of IMPI and lysozyme at 48 h after injection with C. militaris, B. bassiana and sham injection (indicating a wounding response), but this was also prevented by application of cordycepin. These results suggest that cordycepin has potential to act as a suppressor of the immune response during fungal infection of insect hosts.
As the major active ingredient of Cordyceps militaris, cordycepin (3′-deoxyadenosine) has been well documented to possess lipid-lowering and anti-oxidative activities, making it a promising candidate ...for treatment of NAFLD. Autophagy was recently identified as a critical protective mechanism during NAFLD development. Therefore, this study aims to elucidate the mechanism of cordycepin regulating autophagy and lipid metabolism. Here, we found that cordycepin decreased palmitate-induced lipid accumulation by Oil Red O staining, Nile Red staining assays, triglyceride and total cholesterol measurements. Based on Western blot assay and immunocytochemistry, we found that cordycepin induced autophagy in PA-induced steatotic HepG2 cells. Whereas pretreatment with CQ, an autophagy inhibitor, substantially deteriorated the mitigative effects of cordycepin on PA-induced hepatic lipid accumulation. These data taken together indicate that cordycepin protects against PA-induced hepatic lipid accumulation via autophagy induction. Further, cordycepin remarkably increased the expression of P-PKA and decreased P-mTOR, whereas pretreatment with H89, a PKA inhibitor, abolished the ability of cordycepin to activate autophagy via mTOR activation. These data suggested that cordycepin protects against PA-induced hepatic lipid accumulation through the promotion of autophagy. The underlying mechanism might be associated with the PKA/mTOR pathway.
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•Cordycepin decreased palmitate-induced lipid accumulation in HepG2 cells.•Cordycepin induced autophagy in PA-induced steatotic HepG2 cells.•Cordycepin decreased PA-induced hepatic lipid accumulation via autophagy induction.•The underlying mechanism might be associated with the PKA/mTOR pathway.
Cordycepin (COR) has attracted extensive attention for its medical value. Currently, separation and extraction from Cordyceps militaris is the main way to obtain COR, but it is time‐consuming and low ...efficiency. Heterologous synthesis of COR holds great promise for its industrial production. In this work, five COR synthases of different sources were obtained by homology screening, and were integrated into the genome of BY4741. Fermentation and determination of COR found that EA1 and EA2 from Emericellopsis atlantica were more suitable for COR synthesis. Then, ADO1 gene encoding adenosine kinase was knocked down, ADE4 gene encoding amidophosphoribosyltransferase and truncated cpdBN gene encoding 2′,3′‐cyclic‐nucleotide 2′‐phosphodiesterase/3′‐nucleotidase were overexpressed to enhance the accumulation of COR. Finally, the COR titer reached 725.16 mg L−1 in 5‐L bioreactor. This study lays a foundation for the heterologous synthesis and industrial production of COR, and also provides a reference for heterologous synthesis of other high value‐added chemicals.
Cordycepin and kinase inhibition in cancer Khan, Md Asaduzzaman; Tania, Mousumi
Drug discovery today,
March 2023, 2023-03-00, 20230301, Letnik:
28, Številka:
3
Journal Article
Recenzirano
•Kinases are important cellular enzymes but abnormally expressed in cancer.•Kinase inhibitors are potential therapeutic agents against cancer.•Cordycepin is a natural compound with anticancer ...properties.•Cordycepin can interfere with kinase pathways in different cancer.•Cordycepin is a potential kinase inhibitor.
Cordycepin, a nucleoside from Cordyceps mushrooms, has many beneficial properties for health, including anticancer activities. In cancer cells, cordycepin targets various signaling molecules. Here, we review the possible anticancer mechanisms of cordycepin involving the targeting of kinases. Abnormal kinase expression is involved in cancer development and progression through different molecular mechanisms, including phosphorylation, amplification, genetic mutations, and epigenetic regulation. Research suggests that kinases, such as the c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK), AMP kinase (AMPK), phosphoinositide 3-kinase (PI3K)/Akt, extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), glycogen synthase kinase (GSK)-3β, and focal adhesion kinase (FAK) pathways, can be targeted by cordycepin and disrupting their activity. Given that kinase inhibitors can have crucial roles in cancer treatment, targeting kinases might be one of the molecular mechanisms involved in the anticancer potential of cordycepin.
Diabetes mellitus (DM) has recently become one of the major diseases that have received attention. Cordycepin (molecular formula: C10H13N5O3), is one of the major bioactive components of Cordyceps ...militaris, decreases blood glucose levels. In this study, the effect and mechanism of cordycepin in normal and oxidative-damaged INS-1 cells were explored by using cell and molecular biology methods. Results showed that cordycepin could enhance insulin synthesis and secretion. The mechanism is possibly related to the elevated ATP content induced membrane depolarisation and increased Ca2+ concentration. At the genetic level, cordycepin upregulated the mRNA level of insulin, pancreatic duodenal homeobox factor-1 (PDX-1) and glucose transporter 1 (GLUT1). At the protein level, cordycepin promoted the expression of PDX-1, GLUT1, serine threonine kinase (Akt) and phosphorylated Akt (P-Akt). These effects may also contribute to the enhancement of insulin synthesis and secretion. Further analysis revealed that cordycepin protected against H2O2-induced damage on INS-1 cells and improved their viability and insulin synthesis/secretion. This effect should be attributed to the reduced intracellular reactive oxygen species (ROS), enhanced mitochondrial membrane potential (MMP), increased activity of superoxide dismutase (SOD) and upregulated genetic and protein expression of catalase (CAT), PDX-1, GLUT1 and P-Akt. In conclusion, cordycepin promotes insulin synthesis and secretion in normal islet β cells and improves this function in oxidative-damaged islet β cells. Given that islet β cells are vulnerable to oxidative stress, the improving effect of cordycepin on the antioxidant capacity and insulin synthesis/secretion of INS-1 cells may be an important mechanism for its hypoglycaemic effect.
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•Co-overexpression of GLK1 and PGM1 significantly promoted cordycepin accumulation.•Molasses, DHP, and waste yeast as alternate enhanced cordycepin production.•High C/N molar ratio ...and weak acidic were more conducive to producing cordycepin.•The cordycepin productivity in the optimized medium was increased by 28.81%.•Using agro-industrial residues can reduce the cost of cordycepin production.
Cordycepin, a nucleoside compound with a variety of biological activities, has been extensively applied in the nutraceutical and pharmaceutical industries. The advancement of microbial cell factories using agro-industrial residues provides a sustainable pathway for cordycepin biosynthesis. Herein, the cordycepin production was enhanced by the modification of glycolysis and pentose phosphate pathway in engineered Yarrowia lipolytica. Then, cordycepin production based on economical and renewable substrates (sugarcane molasses, waste spent yeast, and diammonium hydrogen phosphate) was analyzed. Furthermore, the effects of C/N molar ratio and initial pH on cordycepin production were evaluated. Results indicated that the maximum cordycepin productivity of 656.27 mg/L/d (72 h) and cordycepin titer was 2286.04 mg/L (120 h) by engineered Y. lipolytica in the optimized medium, respectively. The cordycepin productivity in the optimized medium was increased by 28.81% compared with the original medium. This research establishes a promising way for efficient cordycepin production from agro-industrial residues.
Cordycepin (3′-deoxyadenosine) is a major bioactive agent in Cordyceps militaris, a fungus used in traditional Chinese medicine. It has been proposed to have many beneficial metabolic effects by ...activating AMP-activated protein kinase (AMPK), but the mechanism of activation remained uncertain. We report that cordycepin enters cells via adenosine transporters and is converted by cellular metabolism into mono-, di-, and triphosphates, which at high cordycepin concentrations can almost replace cellular adenine nucleotides. AMPK activation by cordycepin in intact cells correlates with the content of cordycepin monophosphate and not other cordycepin or adenine nucleotides. Genetic knockout of AMPK sensitizes cells to the cytotoxic effects of cordycepin. In cell-free assays, cordycepin monophosphate mimics all three effects of AMP on AMPK, while activation in cells is blocked by a γ-subunit mutation that prevents activation by AMP. Thus, cordycepin is a pro-drug that activates AMPK by being converted by cellular metabolism into the AMP analog cordycepin monophosphate.
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•Cordycepin (100 μM) activates AMPK in human cells; higher concentrations are toxic•Cordycepin is taken up into cells and converted into mono-, di-, and triphosphates•AMPK activation correlates with the cellular content of cordycepin monophosphate•Cordycepin monophosphate mimics all three effects of AMP on AMPK in cell-free assays
Cordycepin is a major bioactive component of Cordyceps militaris, a parasitic fungus much prized in traditional Chinese medicine. Hawley et al. report that it is taken into cells and converted by the metabolism into mono-, di-, and triphosphates. Cordycepin monophosphate activates AMPK by mimicking multiple effects of its natural activator, AMP.
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