Cordycepin, a Metabolic Product isolated from Cultures of Cordyceps militaris (Linn.) Link.

Cunningham, K. G.; Manson, William; Spring, F. S.; Hutchinson, S.A.

doi:10.1038/166949a0

Cited by 293 publications

(174 citation statements)

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“…7 On the other hand, activation of IRE1 results in recruitment and activation of apoptosis signal-regulating kinase 1 (ASK1) and downstream c-Jun N-terminal kinase (JNK), both of which are involved in a wide range of pro-apoptotic processes. 8 These signaling pathways offset the effects of the pro-survival UPR. Based on this current concept, development of agents that selectively reinforce the pro-survival UPR but suppress the pro-apoptotic UPR is an important challenge towards effective treatments for ER stress-related diseases.…”

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confidence: 99%

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Aberrant, differential and bidirectional regulation of the unfolded protein response towards cell survival by 3′-deoxyadenosine

et al. 2011

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The unfolded protein response (UPR) is involved in a diverse range of pathologies triggered by endoplasmic reticulum (ER) stress. Endeavor to seek selective regulators of the UPR is a promising challenge towards therapeutic intervention in ER stressrelated disorders. In the present report, we describe aberrant, differential and bidirectional regulation of the UPR by 3 0 -deoxyadenosine (cordycepin) towards cell survival. 3 0 -Deoxyadenosine blocked ER stress-induced apoptosis via inhibiting the IRE1-JNK pro-apoptotic pathway. 3 0 -Deoxyadenosine also inhibited apoptosis through reinforcement of the pro-survival eIF2a signaling without affecting PERK activity. It was associated with depression of GADD34 that dephosphorylates eIF2a, and dephosphorylation of eIF2a by salubrinal mimicked the anti-apoptotic effect of 3 0 -deoxyadenosine. Unexpectedly, although 3 0 -deoxyadenosine caused activation of eIF2a, it inhibited downstream pro-apoptotic events including induction of ATF4 and expression of CHOP. Cooperation of adenosine transporter and A3 adenosine receptor, but not A1/A2 receptors, mediated the pluripotent effects of 3 0 -deoxyadenosine. In mice, ER stress caused activation of JNK, expression of CHOP and induction of apoptosis in renal tubules. The apoptosis was significantly attenuated by administration with 3 0 -deoxyadenosine, and it was correlated with blunted induction of JNK and CHOP in the kidney. These results disclosed atypical pro-survival regulation of the UPR by 3 0 -deoxyadenosine, which may be advantageous for the treatment of intractable, ER stress-related disorders. Endoplasmic reticulum (ER) stress-mediated tissue injury is implicated in a wide range of pathologies including cancers, infection, atherosclerosis, ischemia, neurodegenerative disorders and metabolic diseases such as diabetes mellitus.

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“…8,9 It possesses a wide range of biological effects including antithrombotic, anti-cancer, anti-viral, anti-fungal and anti-inflammatory activities. In mice, administration of 3 0 -deoxyadenosine reduces tumor formation in a model of metastasis 10 and has been proposed as an anti-cancer drug.…”

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Aberrant, differential and bidirectional regulation of the unfolded protein response towards cell survival by 3′-deoxyadenosine

et al. 2011

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“…Naturally occurring Cordyceps sinensis and its fermentation product Cs-4 contain a broad range of chemical constituents, as summarized by Zhu et al 2 Early investigation showed that Cordyceps species produce two principal constituents: cordycepin and cordycepic acid. Cunningham et al, 16 in 1951, isolated cordycepin and demonstrated its chemical composition. Later, cordycepin, produced by Cordyceps militaris, was identified as 3 0 -deoxyadenosine.…”

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Effect of Cs-4^® (Cordyceps sinensis) on Exercise Performance in Healthy Older Subjects: A Double-Blind, Placebo-Controlled Trial

Chen

Krochmal

et al. 2010

The Journal of Alternative and Complementary Medicine

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Objective: The objective of this study was to examine the effect of Cs-4 Ò (Cordyceps sinensis) on exercise performance in healthy elderly subjects. Design: Twenty (20) healthy elderly (age 50-75 years) subjects were enrolled in this double-blind, placebocontrolled, prospective trial. The subjects were taking either Cs-4 333 mg or placebo capsules 3 times a day for 12 weeks. Measurement: Subjects received baseline screening including physical examination and laboratory tests. Maximal incremental exercise testing was performed on a stationary cycle ergometer using breath-by-breath analysis at baseline and at the completion of the study. Results: After receiving Cs-4 for 12 weeks, the metabolic threshold (above which lactate accumulates) increased by 10.5% from 0.83 AE 0.06 to 0.93 AE 0.08 L=min ( p < 0.02) and the ventilatory threshold (above which unbuffered H þ stimulates ventilation) increased by 8.5% from 1.25 AE 0.11 to 1.36 AE 0.15 L=min. Significant changes in metabolic or ventilatory threshold were not seen for the subjects in the placebo group after 12 weeks, and there were no changes in _ v vo 2 max in either group. Conclusion: This pilot study suggests that supplementation with Cs-4 (Cordyceps sinensis) improves exercise performance and might contribute to wellness in healthy older subjects.

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“…The pharmacological properties of CM have been studied for more than 50 years since cordycepin (3′-deoxyadenosine) was isolated from CM (Cunningham et al, 1950). Cordycepin is a major bioactive component of CM and has been detected in different parts of the CM fruiting body, ranging from 0.16 to 0.25% (w/w) (Yue et al, 2008).…”

Section: Hbe14o-cellsmentioning

confidence: 99%

Cordyceps Extracts and the Major Ingredient, Cordycepin: Possible Cellular Mechanisms of Their Therapeutic Effects on Respiratory Disease

Fung¹,

Ko²

2012

Respiratory Diseases

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Cordycepin, a Metabolic Product isolated from Cultures of Cordyceps militaris (Linn.) Link.

Cited by 293 publications

References 3 publications

Aberrant, differential and bidirectional regulation of the unfolded protein response towards cell survival by 3′-deoxyadenosine

Aberrant, differential and bidirectional regulation of the unfolded protein response towards cell survival by 3′-deoxyadenosine

Effect of Cs-4^® (Cordyceps sinensis) on Exercise Performance in Healthy Older Subjects: A Double-Blind, Placebo-Controlled Trial

Cordyceps Extracts and the Major Ingredient, Cordycepin: Possible Cellular Mechanisms of Their Therapeutic Effects on Respiratory Disease

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Cordycepin, a Metabolic Product isolated from Cultures of Cordyceps militaris (Linn.) Link.

Cited by 293 publications

References 3 publications

Aberrant, differential and bidirectional regulation of the unfolded protein response towards cell survival by 3′-deoxyadenosine

Aberrant, differential and bidirectional regulation of the unfolded protein response towards cell survival by 3′-deoxyadenosine

Effect of Cs-4® (Cordyceps sinensis) on Exercise Performance in Healthy Older Subjects: A Double-Blind, Placebo-Controlled Trial

Cordyceps Extracts and the Major Ingredient, Cordycepin: Possible Cellular Mechanisms of Their Therapeutic Effects on Respiratory Disease

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Effect of Cs-4^® (Cordyceps sinensis) on Exercise Performance in Healthy Older Subjects: A Double-Blind, Placebo-Controlled Trial