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Area of Science:

  • Integrative biology and pharmacology
  • Systems biology and bioinformatics
  • Traditional and complementary medicine

Background:

  • Ophiocordyceps sinensis (Caterpillar Fungus) and Cordyceps militaris are popular medicinal mushrooms in Asian traditional medicine.
  • O. sinensis is standardized for adenosine, a precursor of ATP involved in various physiological processes.
  • Cordycepin (3'-deoxyadenosine) from C. militaris exhibits significant biological activities.

Purpose of the Study:

  • To provide a scientific rationale for the adaptogenic and resilience-supporting effects of O. sinensis, C. militaris, and cordycepin.
  • To explore potential regulatory alignment for these natural compounds in Western countries.
  • To integrate findings from diverse studies using network pharmacology and bioinformatics.

Main Methods:

  • Narrative review integrating chemical, pharmacokinetic, preclinical, and clinical studies.
  • Application of network pharmacology and bioinformatics tools.
  • Analysis of signaling pathways, cytokine production, kinase signaling, and mitochondrial regulation.

Main Results:

  • Common mechanistic hubs include PI3K-Akt, AMPK-mTOR, MAPK, NF-κB, apoptosis, and stress-response pathways.
  • Clinical meta-analyses show adjunctive benefits in renal and pulmonary disorders, despite heterogeneity.
  • Controversy exists regarding cordycepin bioavailability; nanomolar concentrations suggest indirect or systems-level effects.

Conclusions:

  • O. sinensis, C. militaris, and cordycepin share adaptogenic mechanisms for maintaining biological homeostasis.
  • Systems-level network analysis and molecular pharmacology offer complementary insights into their multi-target bioactivity.
  • The review proposes a new regulatory category for resilience-supporting modulators, addressing conceptual and regulatory barriers.