• Korean Journal of Microbiology
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• v.41 no.3
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• pp.236-238
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• 2005

The effect of light on production of cordycepin (3'-deoxyadenosine) was investigated using Cordyceps militaris. Among Cordyceps spp. tested, C. militaris KCTC 6064 was the best for cordycepin production, After 120-hr cultivation of C. militaris KCTC 6064 at $24^{\circ}C$ in YMG broth with light (1,000 lux), 51.6 mg/l of cordycepin was produced. In general, production of cordycepin with light illumination was better than that without light. Cordycepin production under light illumination was enhanced up 96-hr cultivation, whereas after 96-hr, cordycepin production was decreased.

• Korean Journal of Microbiology
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• v.40 no.3
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• pp.217-220
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• 2004

The effect of media composition and culture condition on mycelial growth and cordycepin (3'-deoxyadenosine) production was determined using Cordyceps spp. Among the strains of C. militaris and C. sinensis tested, C. militaris KCTC 6862, C. militaris DGUM 32003 and C. militaris KCTC 16932 were excellent for the production of cordycepin. The optimal temperature and pH for production of cordycepin were $24^{\circ}C$ and pH ranged from 6.0 to 10, respectively. Among various sources of carbon and nitrogen tested, glucose and tryptone were very excellent for the production of cordycepin, respectively. After 5days cultivation with 1% of tryptone with nitrogen source, 39mg/l of cordycepin was produced. However, addition of phosphorus sources reduced the production of cordycepin.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.16 no.12
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• pp.8292-8296
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• 2015

We manufactured a liqueur containing Cordyceps extract. 21 kinds of the liqueur were manufactured and analyzed the cordycepin content, cordycepin stability and alcohol content. Cordycepin content was detected up to $58{\mu}g/mL$ in DL-3(adding Cordyceps militaris and leached for 3 months). Results of Alcohol content analysis, Methanol was not detected in all samples. Ethanol contents showed at 31.4% from the Leaching process for 3 months after distillation, and at 17.2% from the rice wine adding Cordyceps militaris 8 g. In the results of the Cordycepin content stability analysis, the Cordycepin content decreased during storage period little by little, so our considered opinion is that the cordycepin content should be increased slightly when producing as products.

• Natural Product Sciences
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• v.27 no.3
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• pp.187-192
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• 2021

Cordycepin is a characteristic bioactive compound of Cordyceps militaris with various beneficial effects. Cordyceps grows on both grains and insects, and the content of cordycepin varies depending on the cultivation conditions. In this study, the effect of culture conditions on the cordycepin content was analyzed and the extraction conditions were optimized. Analysis of cordycepin content in Pupae-Cordyceps found that it was highly affected by temperature in culture conditions. In the case of mycelium, it grows well at 20 and 25 ℃, but not at 30 ℃. However, the content of cordycepin was highest at 30℃ and less at 20 ℃. The fruiting body also showed a similar tendency: growth was 20 ℃ > 25 ℃ > 30 ℃, but the cordycepin content was 30 ℃ > 25 ℃ > 20 ℃. The content of cordycepin decreased after the fruiting bodies were produced. Next, extraction conditions such as solvent and time were optimized for maximum cordycepin content using response surface methodology (RSM). There was a large difference in the content of cordycepin according to the content of ethanol and the extraction temperature. Through RSM, it was confirmed that the optimum condition for extraction of cordycepin was 48.9 ℃ using 49.0% ethanol, and 160.9 mg/g extract could be obtained under this condition. In conclusion, this study suggested the optimized conditions for the cultivation and extraction of Pupae-Cordyceps for maximizing the content of cordycepin, and this may be applied to the discovery of materials using cordycepin.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.835-842
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• 2016

The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays a crucial role in cancer occurrence by promoting cell proliferation and inhibiting apoptosis. In the present study, we evaluated the effect of a PI3K inhibitor, LY294002, on the chemosensitivity of gastric cancer cells to cordycepin, a predominant functional component of the fungus Cordyceps militaris, in AGS human gastric cancer cells and investigated possible underlying cellular mechanisms. Our results revealed that cordycepin inhibited viability of AGS cells in a concentration-dependent manner and induced apoptosis, as determined by apoptotic cell morphologies and fluorescence-activated cell sorting analysis associated with attenuated activation of the PI3K/Akt signaling pathway. Treatment with cordycepin in combination with a subtoxic concentration of LY294002 enhanced cordycepin-induced cytotoxicity and apoptotic potentials in AGS cells. Sensitization of LY294002 to cordycepin-induced apoptosis was accompanied by activation of caspases (caspases-3, -8, and -9) and was concomitant with poly(ADP-ribose) polymerase cleavage. Moreover, LY294002 up-regulated pro-apoptotic Bax and enhanced truncation of Bid in cordycepin-treated AGS cells, which was connected with increased loss of mitochondrial membrane potential and release of cytochrome c from mitochondria to the cytosol. Taken together, these results indicate that inhibition of the PI3K/Akt signaling pathway could augment cordycepin-induced apoptosis in human gastric cancer cells by up-regulating caspase activity through mitochondrial dysfunction.

• IMMUNE NETWORK
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• v.9 no.6
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• pp.255-264
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• 2009

Background: Chronic low grade inflammation is closely linked to type II diabetes, obesity, and atherosclerosis. Macrophages play a key role in the regulation of pro- or anti-inflammatory actions at the lesion sites of disease. Components of cordyceps militaris, cordycepin and adenosine, have been used for the modulation of inflammatory diseases. The effects of cordycepin in the modulation of macrophages have yet to be be elucidated. We investigated the effects of cordycepin and adenosine on the morphological changes of macrophages under the inflammatory condition of LPS and an anti-inflammatory condition involving high concentrations of adenosine. Methods: We confirmed the mRNA levels of the M1/M2 cytokine genes through RT-PCR and morphological change. Results: LPS-activated macrophages returned to their inactivated original shape, i.e., they looked like naive macrophages, through the treatment with high concentrations of cordycepin ($40{\mu}g/ml$). LPS and adenosine activated macrophages also returned to their original inactivated shapes after cordycepin treatment; however, at relatively higher levels of cordycepin than adenosine. This change did not occur with relatively low concentrations of cordycepin. Adenosine down-regulated the gene expression of M1 cytokines (IL-$1{\beta}$, TNF-${\alpha}$) and chemokines (CX3CR1, RANTES), such as cordycepin. Additionally, M2 cytokines (IL-10, IL-1ra, TGF-${\beta}$) were up-regulated by both cordycepin and adenosine. Conclusion: Based on these observations, both cordycepin and adenosine regulated the phenotypic switch on macrophages and suggested that cordycepin and adenosine may potentially be used as immunomodulatory agents in the treatment of inflammatory disease.

• Journal of Life Science
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• v.24 no.1
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• pp.92-97
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• 2014

Cordycepin, an active component originally isolated from the traditional medicine Cordyceps militaris, is a derivative of the nucleoside adenosine, which has been shown to possess a number of pharmacological properties, including antioxidant and anti-inflammatory activities, immunological stimulation, and antitumor effects. This study was conducted on cultured human prostate carcinoma LNCap cells to elucidate the possible mechanisms by which cordycepin exerts its anticancer activity, which, until now, has remained poorly understood. Cordycepin treatment of LNCap cells resulted in dose-dependent inhibition of cell growth and the induction of apoptotic cell death as detected by an MTT assay, cleavage of poly ADP-ribose polymerase, and annexin V-FITC staining. Flow cytometric analysis revealed that cordycepin resulted in G2/M arrest in cell cycle progression and downregulation of cyclin B1 and cyclin A expression in a concentration-dependent manner. Moreover, the incubation of cells with cordycepin caused a striking induction in the expression of the cyclin-dependent kinase (CDK) inhibitor p21Waf1/Cip1 without affecting the expression of the tumor suppressor p53. It also resulted in a significant increase in the binding of CDK2 and CDC2 to p21. These findings suggest that cordycepin-induced G2/M arrest and apoptosis in human prostate carcinoma cells is mediated through p53-independent upregulation of the CDK inhibitor p21.

• Journal of Life Science
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• v.26 no.7
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• pp.847-854
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• 2016

Cordycepin, a derivative of the nucleoside adenosine, is one of the active components extracted from fungi of genus Cordyceps, and has been shown to have many pharmacological activities. In this study, we investigated the effects of cordycepin on proliferation and apoptosis of human gastric cancer AGS cells, and its possible mechanism of action. Treatment of cordycepin resulted in significant decrease in cell viability of AGS cells in a concentration-dependent manner. A concentration-dependent apoptotic cell death was also measured by agarose gel electrophoresis and flow cytometery analysis. Molecular mechanistic studies of apoptosis unraveled cordycepin treatment resulted in an enhanced expression of tumor necrosis factor-related apoptosis-inducing ligand, death receptor 5 and Fas ligand. Furthermore, up-regulation of pro-apoptotic Bax, and down-regulation of anti-apoptotic Bcl-2 and Bcl-xL expression were also observed in cordycepin-treated AGS cells. These were followed by activation of caspases (caspase-9, -8 and -3), subsequently leading to poly (ADP-ribose) polymerase cleavage. Taken together, these findings indicate that cordycepin induces apoptosis in AGS cells through regulation of multiple apoptotic pathways, including death receptor and mitochondria. Although further mechanical studies are needed, our results revealed that cordycepin can be regarded as a new effective and chemopreventive compound for human gastric cancer treatment.

• Journal of Life Science
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• v.25 no.5
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• pp.607-614
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• 2015

Cancers are the largest cause of mortality and morbidity all over the world. Cordycepin, an adenosine analog, is a major functional component of the Cordyceps species, which has been widely used in traditional Oriental medicine. Over the last decade, this compound has been reported to possess many pharmacological properties, such as an ability to enhance immune function, as well as anti-inflammatory, antioxidant and anti-cancer effects. Recently, numerous studies have reported interesting properties of cordycepin as a chemopreventive agent as well. There is an accumulating body of experimental evidences suggesting that cordycepin impedes cancer progression by promoting apoptosis, inducing cell cycle arrest, modulating intracellular signaling pathways, and inhibiting invasion and metastasis of cancer cells. In many cancer cell lines, cordycepin inhibits growth and cell cycle progression by inducing arrest of the G2/M phase, resulting from the inhibition of retinoblastoma protein phosphorylation and induction of cyclin-dependent kinase inhibitors. To induce apoptosis, cordycepin activates the extrinsic and intrinsic pathways, which promotes reactive oxygen species generation and the downstream activation of kinase cascades. Cordycepin also can activate alternative pathways to cell death such autophagy. In addition, cordycepin can inhibit the pro-metastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the nuclear factor-kappa B and activated protein-1 signaling pathways. In this review, we summarized the variety of action mechanisms by which cordycepin may mediate chemopreventive effects on cancer and discussed the potential of this natural product as a promising therapeutic inhibitor of cancer development.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.1
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• pp.86-92
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• 2014

Cordycepin is the major functional component of Cordyceps species and is widely used in traditional oriental medicine. Cordycepin has been shown to possess many pharmacological properties, such as enhancement of immune function along with anti-inflammatory, antioxidant, anti-aging, and anti-cancer effects. Here, we investigated the inhibitory effects of cordycepin on cell migration and invasion, which are two critical cellular processes that are often deregulated during metastasis, using HCT116 human colorectal carcinoma cells. According to our data, cordycepin at non-cytotoxic concentrations markedly inhibited the motility and invasiveness of HCT116 cells in a time-dependent manner. RT-PCR and Western blotting results indicated that cordycepin reduced the levels of claudin proteins, which are major components of tight junctions (TJs), and induced tightening of TJs. Cordycepin also attenuated the expression and activities of matrix metalloproteinases (MMPs)-2 and -9, whereas levels of tissue inhibitor of metalloproteinases (TIMPs)-1 and -2 were simultaneously elevated. These findings suggest that cordycepin reduces the migration and invasion of HCT116 cells by modulating the activities of TJs and MMPs.