• Journal of the Korean Wood Science and Technology
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• v.48 no.4
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• pp.548-561
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• 2020

Paecilomyces japonica is widely cultured to produce mycelium for medicinal and health food use. Illumination is an important factor in the growth and production of mycelium in submerged culture. The effects of different light-emitting diode (LED) combinations on the growth and cordycepin content as bioactive substances of mycelium were investigated. The results showed that the mycelium dry weights were lower under dark condition and red LED treatments. Dark condition, fluorescent light, and ultraviolet-A failed to increase the cordycepin content. Blue light was necessary to increase the cordycepin content, and a red-to-blue ratio of 3:7 induced the highest cordycepin content. The cordycepin contents of mycelium in submerged culture were significantly higher in a 12 h/day illumination time under red and blue (red-to-blue ratio of 3:7) LED treatments, showing an increase of up to 38% compared with those under the fluorescent-light control condition. The results demonstrated the roles of light with different wavelengths on the biosynthesis of cordycepin as bioactive substances. The low-heat release and replacement of traditional fluorescent lights with low-energy-consuming LEDs could increase the contents of bioactive substances. After optimization of the cordycepin production using response surface methodology (Box-Behnken design) to its canonical form, the optimum combination was found to be as follows: illumination time = 17.7 h/day, sugar content in the medium = 9.7 g/50 mL, and incubation time = 61.2 h. The model predicted a maximum response of 3779.2 ㎍/mL cordycepin yield.

• IMMUNE NETWORK
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• v.9 no.3
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• pp.98-105
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• 2009

Background: It has been recently noticed that type 2 diabetes (T2D), one of the most common metabolic diseases, causes a chronic low-grade inflammation and activation of the innate immune system that are closely involved in the pathogenesis of T2D. Cordyceps militaris, a traditional medicinal mushroom, produces a component compound, cordycepin (3'-deoxyadenosine). Cordycepin has been known to have many pharmacological activities including immunological stimulating, anti-cancer, and anti-infection activities. The molecular mechanisms of cordycepin in T2D are not clear. In the present study, we tested the role of cordycepin on the anti-diabetic effect and anti-inflammatory cascades in LPS-stimulated RAW 264.7 cells. Methods: We confirmed the levels of diabetes regulating genes mRNA and protein of cytokines through RT-PCR and western blot analysis and followed by FACS analysis for the surface molecules. Results: Cordycepin inhibited the production of NO and pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ in LPS-activated macrophages via suppressing protein expression of pro-inflammatory mediators. T2D regulating genes such as $11{\beta}$-HSD1 and PPAR${\gamma}$ were decreased as well as expression of co-stimulatory molecules such as ICAM-1 and B7-1/-2 were also decreased with the increment of its concentration. In accordance with suppressed pro-inflammatory cytokine production lead to inhibition of diabetic regulating genes in activated macrophages. Cordycepin suppressed NF-${\kappa}B$ activation in LPS-activated macrophages. Conclusion: Based on these observations, cordycepin suppressed T2D regulating genes through the inactivation of NF-${\kappa}B$ dependent inflammatory responses and suggesting that cordycepin will provide potential use as an immunomodulatory agent for treating immunological diseases.

• Journal of Practical Agriculture & Fisheries Research
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• v.11 no.1
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• pp.113-123
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• 2009

This study was carried out to determine effects of long-term supply of Cordyceps militaris mycelia on cordycepin content in milk in dairy cows. Ten Holstein cows in the early stages of lactation were divided into two groups. Control group received no supplement whereas treatment group received 6% of C. militaris mycelia of their dry matter intake for 6 months. Feed intake, milk urea nitrogen and somatic cell counts were not affected by long-term supply of C. militaris mycelia for the whole period. In addition, milk yield and milk composition were not affected by long-term supply of C. militaris mycelia at any time of the periods with the exception of milk protein content and yield. The average of milk protein content and yield from the whole period was higher for C. militaris mycelia supplement group than for the control group. As expected, cordycepin in whole blood and milk was not detected in the control group. The range of cordycepin content in the treatment was 0.31~0.38µ/ml and 0.18~0.26(µ/ml for whole blood and milk, respectively. Individual variation was found to be very high and, furthermore cordycepin was undetected in some milk samples. Thus, no clear pattern could be seen in cordycepin content in milk throughout the whole period. Overall, the results of the present study suggest that the transfer efficiency of cordycepin to milk by supplementing C. militaris mycelia in dairy cows was unpredictable and low.

• Journal of Life Science
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• v.23 no.8
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• pp.1032-1040
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• 2013

The comparative effects of fibrinolytic, antioxidative activity and electrophoretical protein patterns with Cordyceps militaris powder (CM) and cordycepin-enriched Cordyceps militaris JLM0636 powder (CCM) and fermented cordycepin-enriched Cordyceps militaris JLM0636 powder by several microscopic organisms were investigated. In addition, nutritional materials such as mineral, protein, and fatty acids were also measured. The protein concentration was higher in CCM than that in CM. The protein concentration in fermented CCM was the highest in CCM treated by Aspergillus kawachii among the various samples. When total protein patterns of CM, CCM, and both fermented CCMs were analyzed by native- and SDS-PAGE, there were slightly varietal differences in electrophoretical protein patterns. Major minerals were K, Ca, Mg, and Zn. Major fatty acids were palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid. Fibrinolytic activity was the highest in the fermented CCM by Bs treatment among the various samples. The ${\alpha},{\alpha}^{\prime}$-diphenyl-${\beta}$-picrylhydrazyl (DPPH) radical scavenging activity was slightly stronger in the CCM treated with Aspergillus kawachii among the various samples; however, these samples all exhibited relatively low levels of activity compared with the butylated hydroxytoluene (BHT). These results may provide the basic data necessary to understand the biological activities and chemical characteristics of Cordyceps militaris JLM0636 powder fermented by several microscopic organisms to develop functional foods.

• Journal of Practical Agriculture & Fisheries Research
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• v.11 no.1
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• pp.53-61
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• 2009

The present experiment was conducted to examine the effects of mycelia of Cordyceps militaris cultured from grains on cordycepin deposition in muscles and plasma glutathione peroxidase activity in finishing Hanwoo steers. Four steers were divided into two groups. Control group received no supplement whereas treatment group received 1 % mycelia of C. militaris of their feed intake for 80 days prior to slaughtering. Final body weight, average daily gain, dry matter intake were not affected by the treatment. But the activity of plasma glutathione peroxidase was numerically higher for the treatment group than for the control group (15.70 vs 9.23 unit). Furthermore, cordycepin deposition in muscles on the treatment group was identified with thin layer chromatography. The results of the present experiment show that cordycepin could be deposited in muscles of Hanwoo beef by feeding mycelia of Cordyceps militaris cultured from grains.

• CELLMED
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• v.2 no.2
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• pp.14.1-14.7
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• 2012

Cordycepin, a nucleoside derivative, was extracted from $Cordyceps$ $sinensis$, and then proved to be a bioactive compound present in traditional Chinese medicine Cordyceps. Early investigations revealed cordycepin possessed anti-microbial activity mainly by inhibiting nucleic acid synthesis. Although cordycepin is not used as antibacterial agents in clinic, its other pharmacological effects and possible mechanisms have gradually been deeply studied. This review serves to summarize the research progress of cordycepin.

• Preventive Nutrition and Food Science
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• v.12 no.3
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• pp.141-147
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• 2007

Cordycepin (3'-deoxyadenosine), which comes from Cordyceps militaris, the Chinese medicinal fungal genus Cordyceps, is used in the treatment of various diseases such as cancer and chronic inflammation. We recently reported that cordycepin has a novel antiplatelet effect through the down regulation of $[Ca^{2+}]_{i}$ and the elevation of cGMP/cAMP production. In this study, we further investigated the effect of cordycepin on collagen-induced platelet aggregation in the presence of cGMP-dependent protein kinase (PKG)- or cAMP-dependent protein kinase (PKA)-inhibitor. PKG inhibitor Rp-8-pCPT-cGMPS potentiated the collagen-induced platelet aggregation, but PKA inhibitor Rp-8-Br-cAMPS did not. However, both Rp-8-pCPT-cGMPS and Rp-8-Br-cAMPS reduced inhibition by cordycepin of collagen-induced platelet aggregation. Moreover, cordycepin inhibited $Ca^{2+}-dependent$ phosphorylation of both 47 kDa- and 20 kDa-protein in the presence of both PKG inhibitor and PKA inhibitor. Taken altogether, these results suggest that the inhibitory effect of cordycepin on collagen-induced platelet aggregation is associated with cGMP/PKG- and cAMP/PKA-pathways, and thus cordycepin may be an efficacious intervention against platelet aggregation-mediated thrombotic disease.

• 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.

• Journal of Microbiology and Biotechnology
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• v.27 no.7
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• pp.1223-1232
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• 2017

Cordyceps militaris, a member of Ascomycota, a mushroom referred to as caterpillar Dong-chung-ha-cho, is commercially valuable because of its high content of bioactive substances, including cordycepin, and its potential for artificial cultivation. Cordycepin (3'-deoxyadenosine) is highly associated with the pharmacological effects of C. militaris. C. militaris is heterothallic in that two mating-type loci, idiomorph MAT1-1 and MAT1-2, exist discretely in two different spores. In this study, nine C. militaris strains were mated with each other to prepare newly bred strains that produced a larger amount of cordycepin than the parent strains. Nine strains of C. militaris were identified by comparing the internal transcribed spacer sequence, and a total of 12 single spores were isolated from the nine strains of C. militaris. After the MAT idiomorph was confirmed by PCR, 36 mating combinations were performed with six single spores with MAT1-1 and the others with MAT1-2. Eight mating combinations were successfully mated, producing stroma with perithecia. Cordycepin content analysis of all strains by high-performance liquid chromatography revealed that the KASP4-bred strain produced the maximum cordycepin among all strains, regardless of the medium and stroma parts. Finally, universal rice primer-PCR was performed to demonstrate that the bred strains were genetically different from the parental strains and new C. militaris strains. These results may be related to the recombination of genes during mating. The newly produced strains can be used to meet the industrial demand for cordycepin. In addition, breeding through mating suggests the possibility of producing numerous cordycepin-producing C. militaris strains.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.483-491
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• 2019

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. ${\beta}$-Amyloid ($A{\beta}$) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed $A{\beta}$ + IBO-induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in $A{\beta}$ + IBO-induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against $A{\beta}$ + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine $A_1$ receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the $A{\beta}$ + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of $A_1R$ is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.