TY - JOUR
T1 - Molecular mechanisms of cordycepin emphasizing its potential against neuroinflammation
T2 - An update
AU - Govindula, Anusha
AU - Pai, Anuja
AU - Baghel, Saahil
AU - Mudgal, Jayesh
N1 - Funding Information:
The authors wish to acknowledge the infrastructural support provided by the Department of Pharmacology, Manipal College of Pharmaceutical Sciences, and Manipal Academy of Higher Education, Manipal-576104, India. The authors also would like to thank the All India Council for Technical Education (AICTE), New Delhi, India for appointing AG under Quality Improvement Programme (QIP) scheme.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/10/5
Y1 - 2021/10/5
N2 - 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, anti-inflammatory, 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 anti-neuroinflammatory property. Cordycepin acts by downregulation of adenosine A2 receptor, inhibition of microglial activation, and subsequent inhibition of several neuroinflammatory markers (NF-κB, NLRP3 inflammasome, IL-1β, iNOS, COX-2, TNF-α, 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 neuroinflammation-associated CNS disorders.
AB - 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, anti-inflammatory, 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 anti-neuroinflammatory property. Cordycepin acts by downregulation of adenosine A2 receptor, inhibition of microglial activation, and subsequent inhibition of several neuroinflammatory markers (NF-κB, NLRP3 inflammasome, IL-1β, iNOS, COX-2, TNF-α, 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 neuroinflammation-associated CNS disorders.
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U2 - 10.1016/j.ejphar.2021.174364
DO - 10.1016/j.ejphar.2021.174364
M3 - Review article
AN - SCOPUS:85111015795
SN - 0014-2999
VL - 908
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
M1 - 174364
ER -