Molecular mechanisms of cordycepin emphasizing its potential against neuroinflammation: An update

Recent research emphasizes the central role of neuroinflammation in complex neurological disorders such as Alzheimer's disease, Parkinson's disease, depression, multiple sclerosis, and traumatic brain injury. Multiple pathological variables with identical molecular mechanisms have been implicated in the development of CNS inflammatory diseases. Therefore, one of the most crucial tasks in the management of CNS disorders is the alleviation of neuroinflammation. However, there are many drawbacks of new pharmacological drugs used in the management of CNS disorders, including medication side effects, and treatment complications. There is a growing inclination towards bioactive constituents of natural origin to unearth the potential remedies. Cordycepin, an adenosine analogue, is one such bioactive constituent with multiple actions, viz., anticancer, antiinflammatory, hepato-protective, antidepressant, anti-Alzheimer's, anti-Parkinsonian and immunomodulatory effects, along with the promotion of remyelination. This review highlights the converging neuroinflammatory targets of cordycepin in Alzheimer's disease, Parkinson's disease, and depression, to substantiate its antineuroinflammatory property. Cordycepin acts by downregulation of adenosine A2 receptor, inhibition of microglial activation, and subsequent inhibition of several neuroinflammatory markers (NF-Kappa B, NLRP3 inflammasome, IL-1 beta, iNOS, COX-2, TNF-alpha, and HMGB1). Cordycepin mitigates LPS-mediated toll-like receptor activation by activating adenosine receptor A1, thereby improving antioxidant enzymes (superoxide dismutase, glutathione peroxidase) levels. These pieces of evidence point to the probable anti-neuroinflammatory mechanisms of cordycepin, which could facilitate the development of new remedies against neuroinflammationassociated CNS disorders.

Automated summary

Recent research highlights the central role of neuroinflammation in complex neurological disorders, emphasizing the importance of reducing neuroinflammation in managing CNS disorders. Natural bioactive compound cordycepin shows potential as a new remedy against neuroinflammation-associated CNS disorders, with anti-inflammatory, anti-depressant, and anti-Alzheimer's properties. Cordycepin targets various inflammatory markers and toll-like receptor activation, providing evidence for its anti-neuroinflammatory mechanisms.