Pharmacological Applications of Cordyceps Fungi

Cordyceps fungi, a group of entomopathogenic ascomycetes, have long been valued in traditional medicine for their diverse bioactive compounds. The principal metabolite, cordycepin (3′-deoxyadenosine), mimics adenosine and interferes with polyadenylation, conferring anti­proliferative, pro­apoptotic and anti­inflammatory properties. Beyond cordycepin, Cordyceps spp. produce polysaccharides, sterols, peptides and nucleosides that exhibit immunomodulatory, antioxidant, antiviral, antitumour and metabolic regulatory effects. Preclinical studies highlight their ability to modulate cytokine profiles, enhance natural killer cell activity, inhibit key inflammatory pathways and promote cellular homeostasis under stress. Clinically relevant applications are emerging in oncology, metabolic disorders, infectious diseases and as adjuvants to radiotherapy. Cultivation advances and metabolic engineering are expanding sustainable production, while novel delivery systems aim to optimise bioavailability. Collectively, the pharmacological profile of Cordyceps fungi positions them as promising candidates for nutraceutical development and adjunctive therapies worldwide.

Research from Nature Portfolio

A pivotal study demonstrated that cordycepin effectively prevents radiation‐induced ulceration in rodent models by inhibiting cellular senescence. Mechanistically, cordycepin binds to AMPK subunits, activating the kinase and promoting p62-dependent autophagic degradation of Keap1, which liberates NRF2 to translocate into the nucleus. Nuclear NRF2 then upregulates antioxidant and cytoprotective genes, reducing DNA damage foci and senescent cell accumulation in irradiated skin, intestine and oral mucosa. These findings identify AMPK and NRF2 activation as therapeutic targets for radioprotection and suggest cordycepin’s potential as an adjunct in radiotherapy to mitigate normal-tissue injury.

Pharmacological Applications of Cordyceps Fungi publication trend

The graph below shows the total number of articles in pharmacological applications of cordyceps fungi across all publications each year (not limited to Nature Index journals).

Technical terms

Cordycepin (3′-deoxyadenosine): A nucleoside analogue lacking a 3′ hydroxyl group, which disrupts RNA polyadenylation and modulates signalling pathways.

AMPK (AMP-activated protein kinase): A cellular energy sensor kinase that regulates metabolism and autophagy in response to AMP/ATP ratios.

NRF2 (nuclear factor erythroid 2–related factor 2): A transcription factor that controls expression of antioxidant and cytoprotective genes upon release from Keap1.

NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells): A transcription factor central to inflammatory responses, cell survival and immune regulation.

Immunomodulation: The alteration of immune system activity, either through enhancement or suppression of specific cell functions or cytokine production.

References

1. Cordycepin for Health and Wellbeing: A Potent Bioactive Metabolite of an Entomopathogenic Medicinal Fungus Cordyceps with Its Nutraceutical and Therapeutic Potential. Molecules (2020).
2. Cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents. Nature Communications (2019).
3. Cordyceps militaris induces apoptosis in ovarian cancer cells through TNF-α/TNFR1-mediated inhibition of NF-κB phosphorylation. BMC Complementary Medicine and Therapies (2020).
4. Cordyceps militaris: An Overview of Its Chemical Constituents in Relation to Biological Activity. Foods (2021).
5. Cordyceps spp.: A Review on Its Immune-Stimulatory and Other Biological Potentials. Frontiers in Pharmacology (2021).