Cordyceps as a multitarget therapeutic platform: biology, bioactive metabolites, and translational challenges

Cordyceps-related fungi have garnered global attention as multifunctional therapeutic resources owing to their exclusive entomopathogenic biology, remarkable metabolic diversity, and expanding pharmaceutical bearing. Recent taxonomic revisions determined by molecular phylogenetics have redefined the traditional notion of Cordyceps, revealing distinct evolutionary lineages with species-specific metabolite profiles and biological functions. This review provides a complete and evidence-based synthesis of the taxonomy, ecology, host interactions, chemical composition, biosynthetic pathways, pharmacological activities, and translational prospects of chief medicinal species, including Ophiocordyceps sinensis, Cordyceps militaris, Cordyceps cicadae, and related taxa. Particular emphasis is placed on cordycepin, the signature bioactive nucleoside, and its integration with broader metabolite networks encompassing polysaccharides, sterols, peptides, and secondary metabolites. Current evidence demonstrates that Cordyceps-derived compounds influence multiple interconnected signaling pathways, including AMPK, PI3K/Akt/mTOR, NF-κB, MAPK, and oxidative stress-response networks, thereby contributing to immunomodulatory, anti-inflammatory, antimicrobial, anticancer, neuroprotective, and metabolic regulatory effects. The review further reviews recent advances in genomics, transcriptomics, metabolomics, biosynthetic gene-cluster analysis, synthetic biology, metabolic engineering, and exactness fermentation technologies that are redesigning Cordyceps research and industrial production. Critical challenges including species authentication, chemical standardization, pharmacokinetic limitations, product reproducibility, safety evaluation, regulatory requirements, and inadequate clinical validation are also discussed. By integrating biological identity, metabolite biosynthesis, molecular mechanisms, and technological innovation within a translational framework, this review positions Cordyceps as a promising systems-level platform for future therapeutics, functional foods, and precision mycotherapy.