• Title, Summary, Keyword: cordycepin

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Optimization of Culture Condition and Media Composition on the Production of Cordycepin by Cordyceps militaris. (Cordycepin 생성을 위한 배양조건 및 배지조성의 최적화)

  • Jo Sung-Jun;Lee Tae-Hee;Chae Dae-Hoon;Han Yeong-Hwan
    • 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.

Effect of Light Conditions on Production of Cordycepin of Cordyceps militaris (광조건이 Codyceps militaris의 Cordycepin 생산에 미치는 영향)

  • Jo Sung-Jun;Lee Tae-Hee;Chae Dae-Hoon;Han Yeong-Hwan
    • 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.

The Analysis of Cordycepin and Alcohol Content in accordance with The Various Manufacturing Process of The Liqueur Containing The Cordyceps Extract (동충하초 추출물을 함유한 리큐르의 제조공정에 따른 Cordycepin 및 Alcohol 함량 분석)

  • Choi, Seon-Hyo;Kwon, Sang-Chul
    • 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.

Inhibition of PI3K/AKT Signaling Pathway Enhances Cordycepin-Induced Apoptosis in Human Gastric Cancer Cells (인체위암 세포에서 PI3K/AKT 신호 전달계 차단에 의한 동충하초 유래 Cordycepin의 Apoptosis 유발 효과 증진)

  • Lee, Hye Hyeon;Jeong, Jin-Woo;Choi, Yung Hyun
    • 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.

Role of Cordycepin and Adenosine on the Phenotypic Switch of Macrophages via Induced Anti-inflammatory Cytokines

  • Shin, Seul-Mee;Moon, Sun-Hee;Park, Yoon-Hee;Kwon, Jeong-Hak;Lee, Seung-Jeong;Lee, Chong-Kil;Cho, Kyung-Hae;Kim, Kyung-Jae
    • 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.

Induction of Apoptotic Cell Death by Cordycepin, an Active Component of the Fungus Cordyceps militaris, in AGS Human Gastric Cancer Cells (동충하초 유래 cordycepin에 의한 AGS 인체 위암세포의 apoptosis 유발)

  • Lee, Hye Hyeon;Jeong, Jin-Woo;Choi, Yung Hyun
    • 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.

Inhibitory Effect of Cordycepin on Human Platelet Aggregation

  • Cho, Hyun-Jeong;Ham, Hye-Seon;Lee, Tae-Kyung;Jung, Young-Jin;Park, Sun-A;Kang, Hyo-Chan;Park, Hwa-Jin
    • Biomedical Science Letters
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    • v.10 no.1
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    • pp.1-8
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    • 2004
  • Cordycepin separated from Cordyceps militaris is a major physiologic active component in Cordyceps militaris. The platelet aggregation is stimulated by $Ca^{2+}$, which is either mobilized from intracellular endoplasmic reticulum or transported from extracellular space. cGMP antagonizes the actions of $Ca^{2+}$. Based on these facts, we have investigated the effects of cordycepin on the mobilization of $Ca^{2+}$ and the production of cGMP on collagen ($10\mu$g/ml)-induced human platelet aggregation. Cordycepin potently stimulated the human platelet aggregation induced by collagen ($10\mu$g/ml) in a dose-dependent manner. Cordycepin (500 $\mu$M) inhibited also the collagen-induced human platelet aggregation in the presence both 1 mM and 2 mM of $CaCl_2$. These are in accord with the results that cordycepin inhibited the $Ca^{2+}$- influx on collagen-induced human platelet aggregation. These results suggest that cordycepin decrease the intracellular $Ca^{2+}$ concentration to inhibit collagen-induced human platelet aggregation. Besides, cordycepin increased the level of cGMP on collagen-induced human platelet aggregation. This result is related with the decrease of intracellular $Ca^{2+}$ concentration, because cGMP inhibits the mobilization of $Ca^{2+}$. In addition, cordycepin inhibited the human platelet aggregation induced by LY -83583, inhibitor of guanylate cyclase. This result suggested that cordycepin inhibit the platelet aggregation by stimulating the activity of guanylate cyclase. In conclusion, we demonstrated that cordycepin might have the antiplatelet function by inhibiting $Ca^{2+}$-mobilization via the stimulation of the production of cGMP.

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Cordycepin Inhibits Migration and Invasion of HCT116 Human Colorectal Carcinoma Cells by Tightening of Tight Junctions and Inhibition of Matrix Metalloproteinase Activity (Cordycepin의 치밀결합 강화 및 MMPs의 활성 억제를 통한 HCT116 인체대장암세포의 이동성 및 침윤성의 억제)

  • Jeong, Jin Woo;Choi, Yung Hyun
    • 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.

Anti-cancer Properties and Relevant Mechanisms of Cordycepin, an Active Ingredient of the Insect Fungus Cordyceps spp., (동충하초 유래 cordycepin의 항암 활성 기전 최근 연구 동향)

  • Jeong, Jin-Woo;Choi, Yung Hyun
    • 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.

Anti-diabetic Effects of CCCA, CMESS, and Cordycepin from Cordyceps militaris and the Immune Responses in Streptozotocin-induced Diabetic Mice

  • Yun, Yun-Ha;Han, Shin-Ha;Lee, Seung-Jeong;Ko, Sung-Kwon;Lee, Chong-Kil;Ha, Nam-Joo;Kim, Kyung-Jae
    • Natural Product Sciences
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    • v.9 no.4
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    • pp.291-298
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    • 2003
  • Anti-diabetic effect of various fractions of Cordyceps militaris (CM), CCCA (crude cordycepin containing adenosine), CMESS (ethanol soluble supernatant), and cordycepin were evaluated in streptozotocin (STZ) induced diabetic mice, CMESS showed potent inhibitory activity of 34.7% in starch-loaded mice (2 g/kg) while acarbose as a positive standard exhibited 37.8% of inhibition rate. After 3 days administration (50 mg/kg), cordycepin (0.2 mg/kg), and acarbose (10 mg/kg) dramatically reduced blood glucose level (inhibition ratio: 46.9%, 48.4% and 37.5% respectively). CCCA that has high contents of cordycepin (0.656 mg/4 mg) did not influence on reducing blood glucose level. The proliferation of splenocytes and peritoneal macrophages derived from STZ-induced diabetic mice administered samples were evaluated out by addition of mitogens to see the stability of the usage of these herbal medicines. Proliferation of T-lymphocyte was significantly decreased; while NO production was increased more than two fold to STZ control in the cordycepin-administered group. Changes of serum enzyme levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were also evaluated. Cordycepin administered group was appeared to acarbose. We conclude that CMESS and cordycepin may be useful tools in the control of blood glucose level in diabetes and promising new drug as an anti-hyperglycemic agent without defects of immune responses and other side effects.