Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in ...Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in vitro and in vivo studies revealed that cordycepin inhibited proliferation and migration in HepG-2 cells and inhibited the growth of HepG-2 xenograft-bearing nude mice by inducing apoptosis.Transcriptome sequencing analysis revealed a total of 403 differential genes,which revealed that cordycepin may play an anti-HCC role by regulating Hippo signaling pathway.The regulatory effects of cordycepin on the Hippo signaling pathway was further investigated using a YAP1 inhibitor.The results demonstrated that cordycepin upregulated the expression of MST1 and LAST1,and subsequently inhibited YAP1,which activated the Hippo signaling pathway.This in turn downregulated the expression of GBP3 and ETV5,and subsequently inhibited cell proliferation and migration.Additionally,YAP1 regulated the expression of Bax and Bcl-2,regulated the mitochondrial apoptotic pathway,and induced apoptosis by upregulating the expression of the caspase-3 protein.In summary,this study reveals that cordycepin exerts its anti-hepatocarcinoma effect through regulating Hippo signaling pathway,and GBP3 and ETV5 may be potential therapeutic targets for hepatocarcinoma.展开更多
Cordycepin is an active component of parasitic fungus, Cordyceps militaris, and investigated for its pharmacologic efficacy. Increasing evidence supports the anti-tumoral effects of Cordycepin in various types of huma...Cordycepin is an active component of parasitic fungus, Cordyceps militaris, and investigated for its pharmacologic efficacy. Increasing evidence supports the anti-tumoral effects of Cordycepin in various types of human solid tumors. We sought to determine the effects of Cordycepin on oral squamous cell carcinoma in vitro and in vivo. Two oral squamous cell carcinoma cell lines, KB and HSC3, were used in this study. Cells were treated with Cordycepin or diluent, followed by determinations of proliferation by sulforhodamine method and apoptosis by TUNEL assay in vitro. For in vivo experiments, tumor cells were transplanted into nude mice, followed by treatment with Cordycepin or control diluent. In addition, cells were examined for expression of adenosine receptor isotypes, and tested whether cordycepin-induced effects were mediated through adenosine receptors by combinatorial treatment of cordycepin and antagonists specific to each isotype of adenosine receptors. Two cell lines expressed protein of all types of adenosine receptors stronger than normal oral keratinocytes. Cordycepin showed anti-proliferating effect and apoptotic effect on both cell lines in vitro in a dose dependent manner. However, any adenosine receptors did not reverse the effect of cordycepin. In our in vivo experiments, cordycepin failed to decrease the tumor volume significantly, and failed to induce more apoptosis of tumor cells. Cordycepin has anti-proliferating effect and induces apoptosis not mediated by adenosine receptor on oral squamous cell carcinoma cells in vitro. However, in vivo results suggest that cordycepin in itself has a limited value as a novel chemotherapeutic agent for oral squamous cell carcinoma.展开更多
A simple, rapid and low-cost method of determination for cordycepin in Cordyceps kyushuensis by capillary zone electrophoresis (CZE) was developed. Based on the finding that there is a high concentration of cordycepin...A simple, rapid and low-cost method of determination for cordycepin in Cordyceps kyushuensis by capillary zone electrophoresis (CZE) was developed. Based on the finding that there is a high concentration of cordycepin in both natural and cultured Cordyceps kyushuensis, the in vitro antitumor activity of cordycepin and the water extracts of Cordyceps kyushuensis has been investigated. This is the first report about the antitumor effect of Cordyceps kyushuensis.展开更多
Binding of cordycepin to the double helical DNA with a high affinity was investigated by CD spectra in this paper. The results proved that uncoiling, unbinding and denaturation of DNA proceeded continuously upon the i...Binding of cordycepin to the double helical DNA with a high affinity was investigated by CD spectra in this paper. The results proved that uncoiling, unbinding and denaturation of DNA proceeded continuously upon the increase of the concentration of cordycepin.展开更多
Layered double hydroxide was investigated as cordycepin delivery nanocarrier for the first time in this study. Negatively charged biomolecule-cordycepin was intercalated in the gallery spaces of [Mg-Al-NO3], which was...Layered double hydroxide was investigated as cordycepin delivery nanocarrier for the first time in this study. Negatively charged biomolecule-cordycepin was intercalated in the gallery spaces of [Mg-Al-NO3], which was corff＇trmed by the results of X-ray diffraction and electrophoretic mobility. Cell experiment suggested that the new bio-LDH nanohybrid could prevent cordycepin decomposition by adenosine deaminase. This new formulation could possibly be used as a novel form cordycepin intravenous injection.展开更多
A novel negatively charged biomolecule-cordycepin has been intercalated within the gallery spaces of [Mg-Al-NO3]. Results of TEM, PXRD and FT-IR spectroscopy confirmed that cordycepin could be intercalated into [Mg-Al...A novel negatively charged biomolecule-cordycepin has been intercalated within the gallery spaces of [Mg-Al-NO3]. Results of TEM, PXRD and FT-IR spectroscopy confirmed that cordycepin could be intercalated into [Mg-Al-NO3] interlayers as the charge-compensating species. Initial studies suggest that the new bioinorganic nanocomposite may be used as a novel inorganic reservoir or carrier of pharmaceutically active compounds.展开更多
The interaction of cordycepin with calf thymus DNA was investigated at physiological pH with drug/DNA molar ratio of 8. The Raman spectroscopy results indicated that the intercalation of high concentration c...The interaction of cordycepin with calf thymus DNA was investigated at physiological pH with drug/DNA molar ratio of 8. The Raman spectroscopy results indicated that the intercalation of high concentration cordycepin and the interaction of cordycepin with PO2 group led to a major reduction of B-form DNA structure in favor of A-form DNA.展开更多
Cordycepin,which has great immunomodulatory activities such as anticancer,antifungal,antivirus,antileukemia and lipid-lowering ones,is the secondary metabolite of Cordyceps militaris(C.militaris).Liquid submerged ferm...Cordycepin,which has great immunomodulatory activities such as anticancer,antifungal,antivirus,antileukemia and lipid-lowering ones,is the secondary metabolite of Cordyceps militaris(C.militaris).Liquid submerged fermentation is the common cultivation process to produce cordycepin.To optimize the fermentation process and improve production,monitoring the cordycepin secretion in the fermentation is essential.The measurement based on chromatography-mass spectrometry methods is generally involved in the complex sample pretreatments and time-consuming separation,so more rapid and convenient methods are required.Matrix-assisted laser desorption ionization mass spectrometry(MALDI-MS)is more attractive for faster and direct detection.Therefore,MALDI-MS detection combined with isotope-labeled internal standard was applied to the measurement of cordycepin content in the fermentation broth and mycelium.This method made accurate quantification of cordycepin in the range of 5-400μg/mL with a relative standard deviation of 5.6%.The recovery rates of fermentation samples after the 1,13,and 25 days were 90.15%,94.27%,and 95.06%,respectively.The contents of cordycepin in the mycelium and fermentation broth were 136 mg/g and 148.39 mg/mL on the 20 th culture day,respectively.The cordycepin secretion curve of the liquid fermentation of C.militaris was real-time traced over 25 days.展开更多
Objective: To study the effect of cordycepin on non-small cell lung cancer cell line H358 proliferation and related gene expression. Methods: C57BL/6 mice were selected as experimental animals, and the mouse model wit...Objective: To study the effect of cordycepin on non-small cell lung cancer cell line H358 proliferation and related gene expression. Methods: C57BL/6 mice were selected as experimental animals, and the mouse model with transplanted tumor was established after non-small cell lung cancer cell line H358 was cultured;the mice with transplanted tumor were divided into the intervention group who received Corbrin Capsule therapy and the model group who received no drug therapy. 30 d after treatment, the expression of proliferation activity indexes, proliferation genes and invasion genes in transplanted tumor tissue were determined. Results: 30 d after treatment, the mRNA expression and protein expression of PCNA and Ki-67 in transplanted tumor lesion of intervention group were significantly lower than those of model group, and Notch-1, Bmi-1, MIF, Rap2a, NGAL and SIRT1 mRNA expression in transplanted tumor lesion were significantly lower than those of model group while PAQR3, LATS1, E-cadherin, ZO-1 and TES mRNA expression were significantly higher than those of model group. Conclusion: Cordycepin can inhibit the proliferation and invasive growth of non-small cell lung cancer cell line H358 in transplanted tumor tissue.展开更多
Objective:To study the effect of cordycepin on proliferation, apoptosis and invasion-related molecule expression in lung cancer cell lines A549. Methods:Lung cancer cell lines A549 were cultured and treated with diffe...Objective:To study the effect of cordycepin on proliferation, apoptosis and invasion-related molecule expression in lung cancer cell lines A549. Methods:Lung cancer cell lines A549 were cultured and treated with different doses of cordycepin (0, 0.25, 0.5, 1.0, 2.0 and 4.0 ng/mL) for 24 h, and then the proliferation, apoptosis and invasion-related molecule mRNA expression in cells were detected. Results:After 0.25, 0.5, 1.0, 2.0 and 4.0 ng/mL cordycepin treatment, Caspase-3, Caspase-8, NOX1 and LATS1 mRNA expression were significantly higher than those after 0 ng/mL cordycepin treatment (P<0.05) while CyclinD1, Bcl-2, c-Myc, c-FLIP, TRAF6, N-cadherin and Vimentin mRNA expression were significantly lower than those after 0 ng/mL cordycepin treatment (P<0.05). The greater the cordycepin dosage, the higher the Caspase-3, Caspase-8, NOX1 and LATS1 mRNA expression, and the lower the CyclinD1, Bcl-2, c-Myc, c-FLIP, TRAF6, N-cadherin and Vimentin mRNA expression. Conclusions: Cordycepin can promote pro-apoptosis gene expression and inhibit pro-proliferation and pro-invasion gene expression in lung cancer cell lines A549.展开更多
As a major contributor to methane production in agriculture,there is a need for a suitable methane inhibitor to reduce ruminant methane emissions and minimize the impact on the climate.This work aimed to explore the i...As a major contributor to methane production in agriculture,there is a need for a suitable methane inhibitor to reduce ruminant methane emissions and minimize the impact on the climate.This work aimed to explore the influence of cordycepin on rumen fermentation,gas production,microbiome and their metabolites.A total of 0.00,0.08,0.16,0.32,and 0.64 g L^(–1)cordycepin were added into fermentation bottles containing 2 g total mixed ration for in vitro ruminal fermentation,and then the gas produced and fermentation parameters were measured for each bottle.Samples from the 0 and 0.64 g L^(–1)cordycepin addition were selected for 16S rRNA gene sequencing and metabolome analysis.The result of this experiment indicated that the addition of cordycepin could linearly increase the concentration of total volatile fatty acid,ammonia nitrogen,the proportion of propionate,valerate,and isovalerate,and linearly reduce ruminal pH and methane,carbon dioxide,hydrogen and total gas production,as well as the methane proportion,carbon dioxide proportion and proportion of butyrate.In addition,there was a quadratic relationship between hydrogen and cordycepin addition.At the same time,the relative abundance of Succiniclasticum,Prevotella,Rikenellaceae_RC9_gut_group,NK4A214_group,Christensenellaceae_R_(7)_group,unclassified_F082,Veillonellaceae_UCG_001,Dasytricha,Ophryoscolex,Isotricha,unclassified_Eukaryota,Methanobrevibacter,and Piromyces decreased significantly after adding the maximum dose of cordycepin.In contrast,the relative abundance of Succinivibrio,unclassified_Succinivibrionaceae,Prevotellaceae_UCG_001,unclassified_Lachnospiraceae,Lachnospira,Succinivibrionaceae_UCG_002,Pseudobutyrivibrio,Entodinium,Polyplastron,unclassified_Methanomethylophilaceae,Methanosphaera,and Candidatus_Methanomethylophilus increased significantly.Metabolic pathways such as biosynthesis of unsaturated fatty acids and purine metabolism and metabolites such as arachidonic acid,adenine,and 2′-deoxyguanosine were also affected by the addition of cordycepin.Based on this,we conclude that cordycepin is an effective methane emission inhibitor that can change the rumen metabolites and fermentation parameters by influencing the rumen microbiome,thus regulating rumen methane production.This experiment may provide a potential theoretical reference for developing Cordyceps byproduct or additives containing cordycepin as methane inhibitors.展开更多
Objective:To explore the molecular mechanism by which cordycepin inhibits cell proliferation and induces apoptosis of human colorectal cancer cells.Methods:Cell counting and MTS(3-(4,5-dimethylthiazol-2-yl)-5-(3-carbo...Objective:To explore the molecular mechanism by which cordycepin inhibits cell proliferation and induces apoptosis of human colorectal cancer cells.Methods:Cell counting and MTS(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium,inner salt) method were used to monitor the effects of cordycepin on cell proliferation.Flow cytometry(FCM) was used to analyze the effects of cordycepin on the cell cycle progress.Annexin V-fluorescein isothiocyanate(FITC) analysis was used to detect apoptosis at a very early stage.Caspase-Glo was used to determine caspase activity and Western blot was used to measure protein expression levels of c-Jun N-terminal kinase(JNK),p38,and Bcl-2 pro-apoptosis family.Results:The numbers of viable SW480 and SW620 cells and the proliferation of these cells were significantly reduced with increases in cordycepin concentration(P<0.01).The cell cycle progression of SW480 and SW620 was arrested at the G0/G1 phase by the addition of cordycepin,and apoptosis rates of cordycepin treatments were increased compared with the control group.Cordycepin-treated cells showed phosphatidylserine valgus,suggesting the existence of early apoptosis.Caspase-3/7 and-9 activity significantly increased and the protein expression levels of JNK,p38,and Bax,Bid,Bim,and Puma from Bcl-2 pro-apoptosis molecules also increased after the treatment with cordycepin.Conclusions:Cordycepin can inhibit SW480 and SW620 cell proliferation and induce apoptosis.Apoptosis might be induced by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules.展开更多
Obesity is a worldwide epidemic. Promoting browning of white adipose tissue(WAT)contributes to increased energy expenditure and hence counteracts obesity. Here we show that cordycepin(Cpn), a natural derivative of ade...Obesity is a worldwide epidemic. Promoting browning of white adipose tissue(WAT)contributes to increased energy expenditure and hence counteracts obesity. Here we show that cordycepin(Cpn), a natural derivative of adenosine, increases energy expenditure, inhibits weight gain, improves metabolic profile and glucose tolerance, decreases WAT mass and adipocyte size, and enhances cold tolerance in normal and high-fat diet-fed mice. Cpn markedly increases the surface temperature around the inguinal WAT and turns the inguinal fat browner. Further investigations show that Cpn induces the development of brown-like adipocytes in inguinal and, to a less degree, epididymal WAT depots. Cpn also increases the expression of uncoupling protein 1(UCP1) and other thermogenic genes in WAT and3T3-L1 differentiated adipocytes, in which AMP-activated protein kinase(AMPK) plays an important role. Our results provide novel insights into the function of Cpn in regulating energy balance, and suggest a potential utility of Cpn in the treatment of obesity.展开更多
Cordycepin(3′-deoxyadenosine) from Cordyceps militaris has been reported to have anti-tumor effects. However, the molecular target and mechanism underlying cordycepin impeding pancreatic cancer cell growth in vitro a...Cordycepin(3′-deoxyadenosine) from Cordyceps militaris has been reported to have anti-tumor effects. However, the molecular target and mechanism underlying cordycepin impeding pancreatic cancer cell growth in vitro and in vivo remain vague. In this study, we reported functional target molecule of cordycepin which inhibited pancreatic cancer cells growth in vitro and in vivo.Cordycepin was confirmed to induce apoptosis by activating caspase-3, caspase-9 and cytochrome c. Further studies suggested that MAPK pathway was blocked by cordycepin via inhibiting the expression of Ras and the phosphorylation of Erk. Moreover, cordycepin caused S-phase arrest and DNA damage associated with activating Chk2(checkpoint kinase 2) pathway and downregulating cyclin A2 and CDK2 phosphorylation. Very interestingly, we showed that cordycepin could bind to FGFR2(KD = 7.77 × 10-9) very potently to inhibit pancreatic cancer cells growth by blocking Ras/Er K pathway. These results suggest that cordycepin could potentially be a leading compound which targeted FGFR2 to inhibit pancreatic cells growth by inducing cell apoptosis and causing cell cycle arrest via blocking FGFR/Ras/ERK signaling for anti-pancreatic cancer new drug development.展开更多
Objective： To evaluate apoptotic effects of cisplatin and cordycepin as single agent or in combination with cytotoxicity in oral cancer cells. Methods： The influences of cisplatin （2.5 μg/mL） and/or cordycapin tr...Objective： To evaluate apoptotic effects of cisplatin and cordycepin as single agent or in combination with cytotoxicity in oral cancer cells. Methods： The influences of cisplatin （2.5 μg/mL） and/or cordycapin treatment （10 or 100 μmol/L） to human OC3 oral cancer cell line were investigated by morphological observation for cell death appearance, methylthiazoletetrazolium （MTT） assay for cell viability, flow cytometry assay for cell apoptosis, and Western blotting for apoptotic protein expressions. Results： Data demonstrated that co-administration of cisplatin （2.5 μg/mL） and cordycepin （10 or 100μmol/L） resulted in the enhancement of OC3 cell apoptosis compared to cisplatin or cordycapin alone treatment （24 h）, respectively （P〈0.05）. In flow cytometry assay, percentage of cells arrested at subG1 phase with co-treatment of cordycepin and cisplatin （30%） was significantly higher than cisplatin （5%） or cordycepin （12%） alone group （P〈0.05）, confirming a synergistically apoptotic effect of cordycepin and cisplatin. In cellular mechanism study, co-treatment of cordycepin and cisplatin induced more stress-activated protein kinase/dun terminal kinase （JNK）, the expressions of caspase-7, and the cleavage of poly ADP-ribose polymerase （PARP） as compared to cisplatin or cordycepin alone treatment （P〈0.05）. Conclusion： Cisplatin and cordycepin possess synergistically apoptotic effect through the activation of JNK/caspase-7/PARP pathway in human OC3 oral cancer cell line.展开更多
Cordycepin was the first adenosine analogue used as an anticancer and antiviral agent, which is extracted from Cordyceps militaris and hasn’t been biosynthesized until now. This study was first conducted to verify th...Cordycepin was the first adenosine analogue used as an anticancer and antiviral agent, which is extracted from Cordyceps militaris and hasn’t been biosynthesized until now. This study was first conducted to verify the role of ribonucleotide reductases(RNRs, the two RNR subunits, RNRL and RNRM) in the biosynthesis of cordycepin by over expressing RNRs genes in transformed C. militaris. Quantitative real-time PCR(qRT-PCR) and western blotting results showed that the m RNA and protein levels of RNR subunit genes were significantly upregulated in transformant C. militaris strains compared to the control strain. The results of the HPLC assay indicated that the cordycepin was significantly higher in the C. militaris transformants carrying RNRM than in the wildtype strain, whereas the RNRML was preferentially downregulated. For the C. militaris transformant carrying RNRL, the content of cordycepin wasn’t remarkably changed. Furthermore, we revealed that inhibiting RNRs with Triapine(3-AP) almost abrogated the upregulation of cordycepin. Therefore, our results suggested that RNRM can probably directly participate in cordycepin biosynthesis by hydrolyzing adenosine, which is useful for improving cordycepin synthesis and helps to satisfy the commercial demand of cordycepin in the field of medicine.展开更多
Cordycepin has the potential to be an alternative to the disputed herbicide glyphosate.However,current laborious and time-consuming production strategies at low yields based on Cordyceps militaris lead to extremely hi...Cordycepin has the potential to be an alternative to the disputed herbicide glyphosate.However,current laborious and time-consuming production strategies at low yields based on Cordyceps militaris lead to extremely high cost and restrict its application in the field of agriculture.In this study,Komagataella phaffii(syn.Pichia pastoris)was engineered to biosynthesize cordycepin from methanol,which could be converted from CO_(2).Combined with fermentation optimization,cordycepin content in broth reached as high as 2.68±0.04 g/L within 168 h,around 15.95 mg/(L⋅h)in productivity.Additionally,a deaminated product of cordycepin was identified at neutral or weakly alkaline starting pH during fermentation.Transcriptome analysis found the yeast producing cordycepin was experiencing severe inhibition in methanol assimilation and peroxisome biogenesis,responsible for delayed growth and decreased carbon flux to pentose phosphate pathway(PPP)which led to lack of precursor supply.Amino acid interconversion and disruption in RNA metabolism were also due to accumu-lation of cordycepin.The study provided a unique platform for the manufacture of cordycepin based on the emerging non-conventional yeast and gave practical strategies for further optimization of the microbial cell factory.展开更多
基金supported by the National Natural Science Foundation of China(81503187)。
文摘Hepatocellular carcinoma(HCC)is one of the common most malignant tumors.This study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of action.The results of in vitro and in vivo studies revealed that cordycepin inhibited proliferation and migration in HepG-2 cells and inhibited the growth of HepG-2 xenograft-bearing nude mice by inducing apoptosis.Transcriptome sequencing analysis revealed a total of 403 differential genes,which revealed that cordycepin may play an anti-HCC role by regulating Hippo signaling pathway.The regulatory effects of cordycepin on the Hippo signaling pathway was further investigated using a YAP1 inhibitor.The results demonstrated that cordycepin upregulated the expression of MST1 and LAST1,and subsequently inhibited YAP1,which activated the Hippo signaling pathway.This in turn downregulated the expression of GBP3 and ETV5,and subsequently inhibited cell proliferation and migration.Additionally,YAP1 regulated the expression of Bax and Bcl-2,regulated the mitochondrial apoptotic pathway,and induced apoptosis by upregulating the expression of the caspase-3 protein.In summary,this study reveals that cordycepin exerts its anti-hepatocarcinoma effect through regulating Hippo signaling pathway,and GBP3 and ETV5 may be potential therapeutic targets for hepatocarcinoma.
文摘Cordycepin is an active component of parasitic fungus, Cordyceps militaris, and investigated for its pharmacologic efficacy. Increasing evidence supports the anti-tumoral effects of Cordycepin in various types of human solid tumors. We sought to determine the effects of Cordycepin on oral squamous cell carcinoma in vitro and in vivo. Two oral squamous cell carcinoma cell lines, KB and HSC3, were used in this study. Cells were treated with Cordycepin or diluent, followed by determinations of proliferation by sulforhodamine method and apoptosis by TUNEL assay in vitro. For in vivo experiments, tumor cells were transplanted into nude mice, followed by treatment with Cordycepin or control diluent. In addition, cells were examined for expression of adenosine receptor isotypes, and tested whether cordycepin-induced effects were mediated through adenosine receptors by combinatorial treatment of cordycepin and antagonists specific to each isotype of adenosine receptors. Two cell lines expressed protein of all types of adenosine receptors stronger than normal oral keratinocytes. Cordycepin showed anti-proliferating effect and apoptotic effect on both cell lines in vitro in a dose dependent manner. However, any adenosine receptors did not reverse the effect of cordycepin. In our in vivo experiments, cordycepin failed to decrease the tumor volume significantly, and failed to induce more apoptosis of tumor cells. Cordycepin has anti-proliferating effect and induces apoptosis not mediated by adenosine receptor on oral squamous cell carcinoma cells in vitro. However, in vivo results suggest that cordycepin in itself has a limited value as a novel chemotherapeutic agent for oral squamous cell carcinoma.
文摘A simple, rapid and low-cost method of determination for cordycepin in Cordyceps kyushuensis by capillary zone electrophoresis (CZE) was developed. Based on the finding that there is a high concentration of cordycepin in both natural and cultured Cordyceps kyushuensis, the in vitro antitumor activity of cordycepin and the water extracts of Cordyceps kyushuensis has been investigated. This is the first report about the antitumor effect of Cordyceps kyushuensis.
文摘Binding of cordycepin to the double helical DNA with a high affinity was investigated by CD spectra in this paper. The results proved that uncoiling, unbinding and denaturation of DNA proceeded continuously upon the increase of the concentration of cordycepin.
文摘Layered double hydroxide was investigated as cordycepin delivery nanocarrier for the first time in this study. Negatively charged biomolecule-cordycepin was intercalated in the gallery spaces of [Mg-Al-NO3], which was corff＇trmed by the results of X-ray diffraction and electrophoretic mobility. Cell experiment suggested that the new bio-LDH nanohybrid could prevent cordycepin decomposition by adenosine deaminase. This new formulation could possibly be used as a novel form cordycepin intravenous injection.
文摘A novel negatively charged biomolecule-cordycepin has been intercalated within the gallery spaces of [Mg-Al-NO3]. Results of TEM, PXRD and FT-IR spectroscopy confirmed that cordycepin could be intercalated into [Mg-Al-NO3] interlayers as the charge-compensating species. Initial studies suggest that the new bioinorganic nanocomposite may be used as a novel inorganic reservoir or carrier of pharmaceutically active compounds.
基金Project 3037014 was supported by the National Natural Science Foundation of China
文摘The interaction of cordycepin with calf thymus DNA was investigated at physiological pH with drug/DNA molar ratio of 8. The Raman spectroscopy results indicated that the intercalation of high concentration cordycepin and the interaction of cordycepin with PO2 group led to a major reduction of B-form DNA structure in favor of A-form DNA.
基金financially supported by Fundamental Research Funds for the Central Universities(Grant No.2019ZY31)the National Natural Science Foundation of China(Grant Nos.21775086 and 31770110)。
文摘Cordycepin,which has great immunomodulatory activities such as anticancer,antifungal,antivirus,antileukemia and lipid-lowering ones,is the secondary metabolite of Cordyceps militaris(C.militaris).Liquid submerged fermentation is the common cultivation process to produce cordycepin.To optimize the fermentation process and improve production,monitoring the cordycepin secretion in the fermentation is essential.The measurement based on chromatography-mass spectrometry methods is generally involved in the complex sample pretreatments and time-consuming separation,so more rapid and convenient methods are required.Matrix-assisted laser desorption ionization mass spectrometry(MALDI-MS)is more attractive for faster and direct detection.Therefore,MALDI-MS detection combined with isotope-labeled internal standard was applied to the measurement of cordycepin content in the fermentation broth and mycelium.This method made accurate quantification of cordycepin in the range of 5-400μg/mL with a relative standard deviation of 5.6%.The recovery rates of fermentation samples after the 1,13,and 25 days were 90.15%,94.27%,and 95.06%,respectively.The contents of cordycepin in the mycelium and fermentation broth were 136 mg/g and 148.39 mg/mL on the 20 th culture day,respectively.The cordycepin secretion curve of the liquid fermentation of C.militaris was real-time traced over 25 days.
文摘Objective: To study the effect of cordycepin on non-small cell lung cancer cell line H358 proliferation and related gene expression. Methods: C57BL/6 mice were selected as experimental animals, and the mouse model with transplanted tumor was established after non-small cell lung cancer cell line H358 was cultured;the mice with transplanted tumor were divided into the intervention group who received Corbrin Capsule therapy and the model group who received no drug therapy. 30 d after treatment, the expression of proliferation activity indexes, proliferation genes and invasion genes in transplanted tumor tissue were determined. Results: 30 d after treatment, the mRNA expression and protein expression of PCNA and Ki-67 in transplanted tumor lesion of intervention group were significantly lower than those of model group, and Notch-1, Bmi-1, MIF, Rap2a, NGAL and SIRT1 mRNA expression in transplanted tumor lesion were significantly lower than those of model group while PAQR3, LATS1, E-cadherin, ZO-1 and TES mRNA expression were significantly higher than those of model group. Conclusion: Cordycepin can inhibit the proliferation and invasive growth of non-small cell lung cancer cell line H358 in transplanted tumor tissue.
基金Surface Project of Natural Science Foundation of China(3077263).
文摘Objective:To study the effect of cordycepin on proliferation, apoptosis and invasion-related molecule expression in lung cancer cell lines A549. Methods:Lung cancer cell lines A549 were cultured and treated with different doses of cordycepin (0, 0.25, 0.5, 1.0, 2.0 and 4.0 ng/mL) for 24 h, and then the proliferation, apoptosis and invasion-related molecule mRNA expression in cells were detected. Results:After 0.25, 0.5, 1.0, 2.0 and 4.0 ng/mL cordycepin treatment, Caspase-3, Caspase-8, NOX1 and LATS1 mRNA expression were significantly higher than those after 0 ng/mL cordycepin treatment (P<0.05) while CyclinD1, Bcl-2, c-Myc, c-FLIP, TRAF6, N-cadherin and Vimentin mRNA expression were significantly lower than those after 0 ng/mL cordycepin treatment (P<0.05). The greater the cordycepin dosage, the higher the Caspase-3, Caspase-8, NOX1 and LATS1 mRNA expression, and the lower the CyclinD1, Bcl-2, c-Myc, c-FLIP, TRAF6, N-cadherin and Vimentin mRNA expression. Conclusions: Cordycepin can promote pro-apoptosis gene expression and inhibit pro-proliferation and pro-invasion gene expression in lung cancer cell lines A549.
基金financially supported by the National Key Research and Development Program of China(2023YFD2000701)the Natural Science Foundation of Heilongjiang Province,China(YQ2023C011)+1 种基金the Key Research and Development Program of Heilongjiang Province,China(Grant no.2022ZX01A24)the Key Laboratory of Low-carbon Green Agriculture in Northeastern China,Ministry of Agriculture and Rural Affairs of China(LCGANE14)。
文摘As a major contributor to methane production in agriculture,there is a need for a suitable methane inhibitor to reduce ruminant methane emissions and minimize the impact on the climate.This work aimed to explore the influence of cordycepin on rumen fermentation,gas production,microbiome and their metabolites.A total of 0.00,0.08,0.16,0.32,and 0.64 g L^(–1)cordycepin were added into fermentation bottles containing 2 g total mixed ration for in vitro ruminal fermentation,and then the gas produced and fermentation parameters were measured for each bottle.Samples from the 0 and 0.64 g L^(–1)cordycepin addition were selected for 16S rRNA gene sequencing and metabolome analysis.The result of this experiment indicated that the addition of cordycepin could linearly increase the concentration of total volatile fatty acid,ammonia nitrogen,the proportion of propionate,valerate,and isovalerate,and linearly reduce ruminal pH and methane,carbon dioxide,hydrogen and total gas production,as well as the methane proportion,carbon dioxide proportion and proportion of butyrate.In addition,there was a quadratic relationship between hydrogen and cordycepin addition.At the same time,the relative abundance of Succiniclasticum,Prevotella,Rikenellaceae_RC9_gut_group,NK4A214_group,Christensenellaceae_R_(7)_group,unclassified_F082,Veillonellaceae_UCG_001,Dasytricha,Ophryoscolex,Isotricha,unclassified_Eukaryota,Methanobrevibacter,and Piromyces decreased significantly after adding the maximum dose of cordycepin.In contrast,the relative abundance of Succinivibrio,unclassified_Succinivibrionaceae,Prevotellaceae_UCG_001,unclassified_Lachnospiraceae,Lachnospira,Succinivibrionaceae_UCG_002,Pseudobutyrivibrio,Entodinium,Polyplastron,unclassified_Methanomethylophilaceae,Methanosphaera,and Candidatus_Methanomethylophilus increased significantly.Metabolic pathways such as biosynthesis of unsaturated fatty acids and purine metabolism and metabolites such as arachidonic acid,adenine,and 2′-deoxyguanosine were also affected by the addition of cordycepin.Based on this,we conclude that cordycepin is an effective methane emission inhibitor that can change the rumen metabolites and fermentation parameters by influencing the rumen microbiome,thus regulating rumen methane production.This experiment may provide a potential theoretical reference for developing Cordyceps byproduct or additives containing cordycepin as methane inhibitors.
基金supported by the Department of Education of Zhejiang Province(No. Y200804636)the Department of Science and Tech-nology of Zhejiang Province(Nos. 2008C23049,2007C23027,and2009C33081)the Natural Science Foundation of Zhejiang Province(No. Y206174),China
文摘Objective:To explore the molecular mechanism by which cordycepin inhibits cell proliferation and induces apoptosis of human colorectal cancer cells.Methods:Cell counting and MTS(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium,inner salt) method were used to monitor the effects of cordycepin on cell proliferation.Flow cytometry(FCM) was used to analyze the effects of cordycepin on the cell cycle progress.Annexin V-fluorescein isothiocyanate(FITC) analysis was used to detect apoptosis at a very early stage.Caspase-Glo was used to determine caspase activity and Western blot was used to measure protein expression levels of c-Jun N-terminal kinase(JNK),p38,and Bcl-2 pro-apoptosis family.Results:The numbers of viable SW480 and SW620 cells and the proliferation of these cells were significantly reduced with increases in cordycepin concentration(P<0.01).The cell cycle progression of SW480 and SW620 was arrested at the G0/G1 phase by the addition of cordycepin,and apoptosis rates of cordycepin treatments were increased compared with the control group.Cordycepin-treated cells showed phosphatidylserine valgus,suggesting the existence of early apoptosis.Caspase-3/7 and-9 activity significantly increased and the protein expression levels of JNK,p38,and Bax,Bid,Bim,and Puma from Bcl-2 pro-apoptosis molecules also increased after the treatment with cordycepin.Conclusions:Cordycepin can inhibit SW480 and SW620 cell proliferation and induce apoptosis.Apoptosis might be induced by enhancing JNK and p38 kinase activity and increasing the protein expression of Bcl-2 pro-apoptotic molecules.
基金supported financially by the National Natural Science Foundation of China (81402983, 81573436)CAMS Innovation Fund for Medical Sciences (CIFMS) 2016-I2M-3–015the National Major Scientific and Technological Special Project for "Significant New Drugs Development" (2015ZX09501005, China)
文摘Obesity is a worldwide epidemic. Promoting browning of white adipose tissue(WAT)contributes to increased energy expenditure and hence counteracts obesity. Here we show that cordycepin(Cpn), a natural derivative of adenosine, increases energy expenditure, inhibits weight gain, improves metabolic profile and glucose tolerance, decreases WAT mass and adipocyte size, and enhances cold tolerance in normal and high-fat diet-fed mice. Cpn markedly increases the surface temperature around the inguinal WAT and turns the inguinal fat browner. Further investigations show that Cpn induces the development of brown-like adipocytes in inguinal and, to a less degree, epididymal WAT depots. Cpn also increases the expression of uncoupling protein 1(UCP1) and other thermogenic genes in WAT and3T3-L1 differentiated adipocytes, in which AMP-activated protein kinase(AMPK) plays an important role. Our results provide novel insights into the function of Cpn in regulating energy balance, and suggest a potential utility of Cpn in the treatment of obesity.
基金Strategic Priority Research Program of the Chinese Academy of Sciences (No.XDA12010302)National Natural Science Foundation of China(No. 31230022)Program of Shanghai Subject Chief Scientist(No. 16XD1404500)。
文摘Cordycepin(3′-deoxyadenosine) from Cordyceps militaris has been reported to have anti-tumor effects. However, the molecular target and mechanism underlying cordycepin impeding pancreatic cancer cell growth in vitro and in vivo remain vague. In this study, we reported functional target molecule of cordycepin which inhibited pancreatic cancer cells growth in vitro and in vivo.Cordycepin was confirmed to induce apoptosis by activating caspase-3, caspase-9 and cytochrome c. Further studies suggested that MAPK pathway was blocked by cordycepin via inhibiting the expression of Ras and the phosphorylation of Erk. Moreover, cordycepin caused S-phase arrest and DNA damage associated with activating Chk2(checkpoint kinase 2) pathway and downregulating cyclin A2 and CDK2 phosphorylation. Very interestingly, we showed that cordycepin could bind to FGFR2(KD = 7.77 × 10-9) very potently to inhibit pancreatic cancer cells growth by blocking Ras/Er K pathway. These results suggest that cordycepin could potentially be a leading compound which targeted FGFR2 to inhibit pancreatic cells growth by inducing cell apoptosis and causing cell cycle arrest via blocking FGFR/Ras/ERK signaling for anti-pancreatic cancer new drug development.
基金Supported by National Science Council Grant(No.982320-B-006-016),Taiwan,China
文摘Objective： To evaluate apoptotic effects of cisplatin and cordycepin as single agent or in combination with cytotoxicity in oral cancer cells. Methods： The influences of cisplatin （2.5 μg/mL） and/or cordycapin treatment （10 or 100 μmol/L） to human OC3 oral cancer cell line were investigated by morphological observation for cell death appearance, methylthiazoletetrazolium （MTT） assay for cell viability, flow cytometry assay for cell apoptosis, and Western blotting for apoptotic protein expressions. Results： Data demonstrated that co-administration of cisplatin （2.5 μg/mL） and cordycepin （10 or 100μmol/L） resulted in the enhancement of OC3 cell apoptosis compared to cisplatin or cordycapin alone treatment （24 h）, respectively （P〈0.05）. In flow cytometry assay, percentage of cells arrested at subG1 phase with co-treatment of cordycepin and cisplatin （30%） was significantly higher than cisplatin （5%） or cordycepin （12%） alone group （P〈0.05）, confirming a synergistically apoptotic effect of cordycepin and cisplatin. In cellular mechanism study, co-treatment of cordycepin and cisplatin induced more stress-activated protein kinase/dun terminal kinase （JNK）, the expressions of caspase-7, and the cleavage of poly ADP-ribose polymerase （PARP） as compared to cisplatin or cordycepin alone treatment （P〈0.05）. Conclusion： Cisplatin and cordycepin possess synergistically apoptotic effect through the activation of JNK/caspase-7/PARP pathway in human OC3 oral cancer cell line.
基金the Natural Sciences Foundation of China Science (Nos.81872959, 81373920,30801522)Sichuan Province Youth Innovation Team Fund (No.19CXTD0055)China Scholarship Fund (No. 201708570027)。
文摘Cordycepin was the first adenosine analogue used as an anticancer and antiviral agent, which is extracted from Cordyceps militaris and hasn’t been biosynthesized until now. This study was first conducted to verify the role of ribonucleotide reductases(RNRs, the two RNR subunits, RNRL and RNRM) in the biosynthesis of cordycepin by over expressing RNRs genes in transformed C. militaris. Quantitative real-time PCR(qRT-PCR) and western blotting results showed that the m RNA and protein levels of RNR subunit genes were significantly upregulated in transformant C. militaris strains compared to the control strain. The results of the HPLC assay indicated that the cordycepin was significantly higher in the C. militaris transformants carrying RNRM than in the wildtype strain, whereas the RNRML was preferentially downregulated. For the C. militaris transformant carrying RNRL, the content of cordycepin wasn’t remarkably changed. Furthermore, we revealed that inhibiting RNRs with Triapine(3-AP) almost abrogated the upregulation of cordycepin. Therefore, our results suggested that RNRM can probably directly participate in cordycepin biosynthesis by hydrolyzing adenosine, which is useful for improving cordycepin synthesis and helps to satisfy the commercial demand of cordycepin in the field of medicine.
基金support from Open Funding Project of State Key Laboratory of Microbial Metabolism(No.MMLKF20-09)Research Project of Applied Basic Research Program of Department of Science&Technology of Liaoning Province(2022JH2/101300137)+1 种基金the Project of Natural Science Foundation of Liaoning Province(2022-KF-15-02)Science Research Foundation of Educational Department of Liaoning Province(No.J2020099).
文摘Cordycepin has the potential to be an alternative to the disputed herbicide glyphosate.However,current laborious and time-consuming production strategies at low yields based on Cordyceps militaris lead to extremely high cost and restrict its application in the field of agriculture.In this study,Komagataella phaffii(syn.Pichia pastoris)was engineered to biosynthesize cordycepin from methanol,which could be converted from CO_(2).Combined with fermentation optimization,cordycepin content in broth reached as high as 2.68±0.04 g/L within 168 h,around 15.95 mg/(L⋅h)in productivity.Additionally,a deaminated product of cordycepin was identified at neutral or weakly alkaline starting pH during fermentation.Transcriptome analysis found the yeast producing cordycepin was experiencing severe inhibition in methanol assimilation and peroxisome biogenesis,responsible for delayed growth and decreased carbon flux to pentose phosphate pathway(PPP)which led to lack of precursor supply.Amino acid interconversion and disruption in RNA metabolism were also due to accumu-lation of cordycepin.The study provided a unique platform for the manufacture of cordycepin based on the emerging non-conventional yeast and gave practical strategies for further optimization of the microbial cell factory.
