Introduction
Cordycepin has been reported to exhibit hepatic protective and anti‐inflammatory properties. Here, we investigated the role of cordycepin in ischemia/reperfusion (IR)‐induced liver ...injury in a mouse model.
Methods
Mice were pretreated with cordycepin by gavage for 3 weeks, followed by the establishment of the IR modeling. Liver injury, Suzuki's histological grading, hepatic apoptosis, and inflammatory responses were evaluated by biochemical and pathological analysis.
Results
It was found that Cordycepin pretreatment at 50 mg/kg for 3 weeks attenuated IR‐induced liver injury, as reflected by the significant decrease of the levels of aspartate aminotransferase, alanine transaminase, lactate dehydrogenase, and low‐density lipoprotein. Cordycepin pretreatment also reduced histopathological changes, attenuated hepatocyte apoptosis, inflammatory responses in the livers of IR mice. Mechanically, toll‐like receptor 4/nuclear factor kappa‐B signaling in liver tissues was inhibited by Cordycepin pretreatment.
Conclusions
In conclusion, Cordycepin pretreatment protects IR‐induced liver injury, which demonstrates its potential for the treatment of IR in the liver.
Cordycepin pretreatment reduced apoptosis and inflammation markedly in ischemia/reperfusion (IR) liver. Cordycepin protects and improves liver functions in IR mouse model.
Leukemia stem cells (LSCs) are a limitless cell source for the initiation and maintenance of leukemia. Activation of the Wnt/β-catenin pathway is required for the survival and development of LSCs. ...Therefore, targeting β-catenin is considered a therapeutic strategy for the treatment of leukemia. The goal of this study was to explore whether cordycepin, an active component of the traditional medicine Cordyceps sinensis, regulates β-catenin expression in leukemia cells.
In this study, we found that cordycepin significantly suppressed cell proliferation in all malignant cancer cells, including U937, K562, A549, HepG2, SK-Hep1 and MCF7 in a dose-dependent manner. However, cordycepin reduced β-catenin levels in U937, K562 and THP1 leukemia cells and had no effect on other solid cancer cells. In addition, treatment with cordycepin significantly suppressed leukemia colony formation in soft agar assay. Cordycepin enhanced proteasome-dependent degradation and inhibited nuclear translocation of β-catenin in leukemia cells. Cordycepin-reduced β-catenin stability was restored by the addition of a pharmacological inhibitor of GSK-3β, indicating that cordycepin-suppressed β-catenin stability is mediated by the activation of GSK-3β. Furthermore, cordycepin abolished the effect of Wnt3a-induced β-catenin in leukemia cells. In addition, cordycepin-impaired β-catenin is regulated by Akt activation but is not significantly influenced by AMPK or mTOR signal pathways.
Our findings show for the first time that codycepin selectively reduces β-catenin stability in leukemia but not in other solid tumor cells. This suppressive effect is mediated by regulating GSK-3β. A synergistic combination of cordycepin with other treatments should be used as a novel strategy to eradicate leukemia via elimination of LSCs.
To improve S-Adenosyl-L-methionine (a compound with important physiological functions, SAM) production, atmospheric and room temperature plasma and ultraviolet-LiCl mutagenesis were carried out with
...Saccharomyces cerevisiae
strain ZY 1–5. The mutants were screened with ethionine, L-methionine, nystatin and cordycepin as screening agents. Adaptive evolution of a positive mutant UV6-69 was further performed by droplet microfluidics cultivation with ethionine as screening pressure. After adaptation, mutant T11-1 was obtained. Its SAM titer in shake flask fermentation reached 1.31 g/L, which was 191% higher than that of strain ZY 1–5. Under optimal conditions, the SAM titer and biomass of mutant T11-1 in 5 L bioreactor reached 10.72 g/L and 105.9 g dcw/L (142.86% and 34.22% higher than those of strain ZY 1–5), respectively. Comparative transcriptome analysis between strain ZY 1–5 and mutant T11-1 revealed the enhancements in TCA cycle and gluconeogenesis/glycolysis pathways as well as the inhibitions in serine and ergosterol synthesis of mutant T11-1. The elevated SAM synthesis of mutant T11-1 may attribute to the above changes. Taken together, this study is helpful for industrial production of SAM.
Cordyceps militaris is currently exploited for commercial production of specialty products as its biomass constituents are enriched in bioactive compounds, such as cordycepin. The rational process ...development is important for economically feasible production of high quality bioproducts. Light is an abiotic factor affecting the cultivation process of this entomopathogenic fungus, particularly in its carotenoid formation. To uncover the cell response to light exposure, this study aimed to systematically investigate the metabolic responses of C. militaris strain TBRC6039 using integrative genome-wide transcriptome and genome-scale metabolic network (GSMN)-driven analysis. The genome-wide transcriptome analysis showed 8747 expressed genes in the glucose and sucrose cultures grown under light-programming and dark conditions. Of them, 689 differentially expressed genes were significant in response to the light-programming exposure. Through integration with the GSMN-driven analysis using the improved network (iRT1467), the reporter metabolites, e.g., adenosine-5'-monophosphate (AMP) and 2-oxoglutarate, were identified when cultivated under the carotenoid-producing condition controlled by light-programming exposure, linking to up-regulations of the metabolic genes involved in glyoxalase system, as well as cordycepin and carotenoid biosynthesis. These results indicated that C. militaris had a metabolic control in acclimatization to light exposure through transcriptional co-regulation, which supported the cell growth and cordycepin production in addition to the accumulation of carotenoid as a photo-protective bio-pigment. This study provides a perspective in manipulating the metabolic fluxes towards the target metabolites through either genetic or physiological approaches.
Cordycepin, also known as 3-deoxyadenosine, is an analogue of adenosine extracted from the traditional Chinese medicine "Dong Chong Xia Cao". Cordycepin is an active small molecular weight compound ...and is implicated in modulating multiple physiological functions including immune activation, anti-aging and anti-tumor effects. Several studies have indicated that cordycepin suppresses tumor progression. However, the signaling pathways involved in cordycepin regulating cancer cell motility, invasiveness and epithelial-mesenchymal transition (EMT) remain unclear. In this study, we found that cordycepin inhibits hepatocellular carcinoma (HCC) cell proliferation and migration/invasion. Treatment of cordycepin results in the increasing expression of epithelial marker, Ecadherin while no significant effect was found on N-cadherin α-catenin and β-catenin. Furthermore, although the expression of focal adhesion kinase (FAK) was slightly reduced, the level of phosphorylated FAK was significantly reduced by the treatment of cordycepin. In addition, cordycepin significantly suppresses the expression of integrin α3, integrin α6 and integrin β1 which are crucial interacting partners of FAK in regulating the focal adhesion complex. These results suggest cordycepin may contribute to EMT, antimigration/ invasion and growth inhibitory effects of HCC by suppressing E-cadherin and integrin/FAK signaling. Thus, cordycepin is a potential therapeutic or supplementary agent for preventing HCC tumor progression.
Cordycepin is a purine nucleoside analog with potent and diverse biological activities. Herein, we designed two methods to synthesize cordycepin. One method mainly converted the 3′-OH group into an ...iodide group and further dehalogenation to yield the final product. Although this method presented a short synthetic procedure, the synthesis had a low overall yield, resulting in only 13.5% overall yield. To improve the overall yield of cordycepin, another synthetic route was studied, which consisted of four individual steps: (1) 5′-OH protection (2) esterification (3) -
O
-tosyl (-OTs) group removal (4) deprotection. The key step in the synthetic method involved the conversion of 5′-
O
-triphenylmethyladenosine to 3′-
O
-tosyl-5′-
O
-triphenylmethyladenosine, using LiAlH
4
as reducing agent. The main advantages of this route were an acceptable total product yield and the commercial availability of all starting materials. The optimal reaction conditions for each step of the route were identified. The overall yield of cordycepin obtained from adenosine as the starting material was 36%.
Compound cordycepin (3′‐deoxyadenosine) has been used in cancer treatment, diabetes prevention, and anti‐virus, as well as hyperlipidemia downregulation in vivo. However, the association between ...lipid metabolism and mitochondrial activity in cordycepin‐treated hepatocytes is remain unclear. In this study, whether cordycepin affects lipogenesis and fatty beta‐oxidation through regulating mitochondrial activity and AMP‐activated protein kinase (AMPK) in hepatocytes were investigated. The data showed that cordycepin decreased lipid accumulation via activating AMPK and regulating mitochondrial function in oleic acid (OA)‐induced mouse FL83B hepatocytes while the anti‐fatty liver effect of cordycepin on regulating lipogenesis and fatty beta‐oxidation was abolished by AMPK inhibitor compound C treatment. These results suggested that cordycepin attenuated lipid accumulation through promoting beta‐oxidation and may be developed as a functional food/natural medicine for fatty liver suppression.
Practical applications
Traditional herb, Chinese medicine, and functional food treatments for hyperlipidemia are relatively cheap and locally available. The results of this study suggested that cordycepin (active compound of Cordyceps) may be developed as functional foods for fatty liver treatment via regulating fatty beta‐oxidation.
A fast, reliable and reproducible UHPLC-IMS method was developed and validated for simultaneous determination of eight nucleosides (adenine, adenosine, cordycepin, guanosine, inosine, thymidine, ...thymine and uracil) in natural Ophiocordyceps sinensis. Present study was conducted to determine the marker nucleoside contents in low quantities using the developed method. Methanol and water in combination were used as extraction solvents due to hydrophilic nature of nucleosides. These nucleosides showed good linearity (r
2
>0.99), LOD (0.28-0.97ng/mL), LOQ (0.79-3.20 ng/mL), recoveries (88.3 and 103.2%), reproducibility, stability and intra- and inter-day precision (<2.87%). Method was validated using three samples of natural Ophiocordyceps collected from different geographical region. PCA analysis depicted that adenine, adenosine, guanine, guanosine, uracil and uridine were major components contributing to total variance. Highest nucleosides content (5124 µg/g) was detected in STD-1. The presence of cordycepin, an important marker compound was identified for first time using ion mobility mass spectrometry (IMMS) technique. Metabolomics approach resulted 18, 12 and 9 metabolites in three samples (STD-1, STD-II and STD-III, respectively) using METLIN database which opened the new avenues to identify and explore more novel biomarkers in Ophiocordyceps. We anticipate that these methods may be applied to verify/certification of Ophiocordyceps containing marker nucleosides for their dietary intake.
Objectives: Atopic dermatitis (AD) is an allergic and inflammatory skin disorder caused by a combination of itching and skin sensitization by allergens. This article investigated whether cordycepin ...modulates AD symptoms by using an AD murine model.
Material and methods: We evaluated a regulatory effect and specific molecular mechanism of cordycepin on AD induced by the repeated local exposure of 2,4-dinitrochlorobenzene to dorsal skin of mice. Blood or AD-like skin lesions samples were removed for histopathologic analysis, enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and Western blot analyses.
Results: Oral administration of cordycepin decreased duration of scratching behavior and serum levels of histamine and immunoglobulin E increased by DNFB challenge. Cordycepin attenuated clinical symptoms and epidermis thickness of AD mice. In addition, cordycepin reduced thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-6, and tumor necrosis factor-α levels in the serum of AD mice. Cordycepin-attenuated infiltrations of mast cells and eosinophils with decreases in TSLP, macrophage inflammatory protein-2, and intercellular adhesion molecule-1 protein levels in AD-like skin lesions. Messenger RNA expressions of TSLP, thymus and activation-regulated chemokine/CCL17, and C-C chemokine receptor type 3 in AD-like skin lesions were also suppressed by cordycepin. Cordycepin inhibited caspase-1 expressions and activities in AD-like skin lesions.
Conclusions: In conclusion, this study demonstrates that cordycepin ameliorates AD symptoms, suggesting that cordycepin might be a candidate to treat allergic skin diseases.
In this study, the main bioactive compounds of the fruit bodies of Cordyceps militaris-such as adenosine, cordycepin, polysaccharides, mannitol, superoxide dismutase (SOD), and carotenoids-were ...cultivated on wheat and pupae, as well as sclerotium (the pupae portion) and sclerotium with fruiting bodies. The amounts of adenosine and polysaccharide in all the tested samples (except for the polysaccharides of sclerotium) are higher than the quality standards (adenosine ≥0.055% and polysaccharide ≥2.5%) determined by the Ministry of Health of the People's Republic of China. As the most important bioactive compound in C. militaris, cordycepin is the highest in the fruiting bodies on pupae than in other samples, whereas it is the lowest in the sclerotium. The amounts of cordycepin, carotenoids, and SOD were higher in the fruiting bodies on pupae than that in the fruiting bodies on wheat, whereas the amounts of adenosine, polysaccharides, and mannitol were higher in the fruiting bodies on wheat than in the fruiting bodies on pupae. There was no significant difference in the amounts of cordycepin, carotenoids, and SOD in the sclerotium with fruiting bodies and the fruiting bodies on wheat. The adenosine, polysaccharide, and mannitol contents in the sclerotium with fruiting bodies were significantly lower than those of the fruiting bodies on wheat. Overall, the results of this evaluation could not distinguish which is better: the fruiting bodies on pupae or those on wheat; each has its own merits. The fruiting bodies of C. militaris cultivated on both wheat and pupae are important candidates for medicinal and tonic use for the welfare of humankind.
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