Therapeutic Potential and Biological Applications of Cordycepin and Metabolic Mechanisms in Cordycepin-Producing Fungi

Abstract

Cordycepin (3′-deoxyadenosine), a cytotoxic nucleoside analogue found in Cordyceps militaris, has attracted much attention due to its therapeutic potential and biological value. Cordycepin interacts with multiple medicinal targets associated with cancer, tumor, inflammation, oxidant, polyadenylation of mRNA, etc. The investigation of the medicinal drug actions supports the discovery of novel targets and the development of new drugs to enhance the therapeutic potency and reduce toxicity. Cordycepin may be of great value owing to its medicinal potential as an external drug, such as in cosmeceutical, traumatic, antalgic and muscle strain applications. In addition, the biological application of cordycepin, for example, as a ligand, has been used to uncover molecular structures. Notably, studies that investigated the metabolic mechanisms of cordycepin-producing fungi have yielded significant information related to the biosynthesis of high levels of cordycepin. Here, we summarized the medicinal targets, biological applications, cytotoxicity, delivery carriers, stability, and pros/cons of cordycepin in clinical applications, as well as described the metabolic mechanisms of cordycepin in cordycepin-producing fungi. We posit that new approaches, including single-cell analysis, have the potential to enhance medicinal potency and unravel all facets of metabolic mechanisms of cordycepin in Cordyceps militaris.

N6-(2-hydroxyethyl)-Adenosine Induces Apoptosis via ER Stress and Autophagy of Gastric Carcinoma Cells In Vitro and In Vivo

“…Both HEA and cordycepin (3ʹ-deoxyadenosine) are main components of Cordyceps species and are also analogues of adenosine. The antitumor effect of cordycepin has been widely reported, but studies on HEA antineoplastic activity are relatively few [ 6 , 23 , 24 ]. Previous studies have shown that EEC has an antitumor effect, and HEA is one of the main components of EEC, but no in-depth study has been conducted [ 13 ].…”

Cordycepin for Health and Wellbeing: A Potent Bioactive Metabolite of an Entomopathogenic Medicinal Fungus Cordyceps with Its Nutraceutical and Therapeutic Potential

“…Moreover, there are a few reports indicating that Cordyceps intake can cause lead poisoning in some cases. Considering the potential for toxicity, resistance and its efficiency, potential drug derivatives designed from the natural products for the adenosine deaminase-resistant properties and low-toxicity causing effects of cordycepin, as well as organ-targeted nanoparticles for cordycepin delivery for in vivo therapy, are also needed [146].…”

“…Moreover, there are a few reports indicating that Cordyceps intake can cause lead poisoning in some cases. Considering the potential for toxicity, resistance and its efficiency, potential drug derivatives designed from the natural products for the adenosine deaminase-resistant properties and low-toxicity causing effects of cordycepin, as well as organ-targeted nanoparticles for cordycepin delivery for in vivo therapy, are also needed [ 146 ]. Further clinical, experimental as well as epidemiological data are required for identification of other molecular targets to see the correlation between Cordyceps and other diseases like cancers and to estimate the validation of optimum dosing for its safety and efficacy [ 28 ].…”

Bioactive Metabolites and Potential Mycotoxins Produced by Cordyceps Fungi: A Review of Safety

“…Cordycepin can inhibit RNA synthesis and has demonstrated immense medicinal potential ( Table 1 ), including anti-cancer, anti-inflammatory, antibiotic, anti-virus, and antioxidant activities [ 31 ]. However, in addition to its dosage-dependent toxicity to different cells, cordycepin has shown an effect in stimulating testosterone production in the models of both mouse Ledydig cells and mice, which may alter male fertility [ 32 ]. Recently, it has been shown that the anti-leukemia drug pentostatin ( Figure 2 ), i.e., the 2’-deoxycoformycin originally isolated from Streptomyces antibioticus being an irreversible inhibitor of adenosine deaminase, can also be produced by C. militaris through the same BGC for cordycepin production via a protector–protégé strategy [ 19 ].…”