Effects of cordycepin on the microglia-overactivation-induced impairments of growth and development of hippocampal cultured neurons.
Microglial cells are normally activated in response to brain injury or immunological stimuli to protect central nervous system (CNS). However, over-activation of microglia conversely amplifies the inflammatory effects and mediates cellular degeneration, leading to the death of neurons. Recently, cordycepin, an active component found in Cordyceps militarisa known as a rare Chinese caterpillar fungus, has been reported as an effective drug for treating inflammatory diseases and cancer via unclear mechanisms. In this study, we attempted to identify the anti-inflammatory role of cordycepin and its protective effects on the impairments of neural growth and development induced by microglial over-activation. The results indicate that cordycepin could attenuate the lipopolysaccharide (LPS)-induced microglial activation, evidenced by the dramatically reduced release of TNF-α and IL-1β, as well as the down-regulation of mRNA levels of iNOS and COX-2 after cordycepin treatment. Besides, cordycepin reversed the LPS-induced activation of NF-κB pathway, resulting in anti-inflammatory effects. Furthermore, by employing the conditioned medium (CM), we found cordycepin was able to recover the impairments of neural growth and development in the primary hippocampal neurons cultured in LPS-CM, including cell viability, growth cone extension, neurite sprouting and outgrowth as well as spinogenesis. This study expands our knowledge of the anti-inflammatory function of cordycepin and paves the way for the biomedical applications of cordycepin in the therapies of neural injuries.
Wuzhong Hospital, Suzhou, Jiangsu, China.
Jie
J
Peng
Wuzhong Hospital, Suzhou, Jiangsu, China.
Ping
P
Wang
The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Hongshan
H
Ge
School of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, NSW, Australia.
Xianqin
X
Qu
The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Sydney Centre for Regenerative and Developmental Medicine, Kolling Institute for Medical Research, Sydney Medical School, University of Sydney, NSW, Australia.
Xingliang
X
Jin
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003839:Deoxyadenosines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D007249:Inflammation / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D000066829:Neuroprotection / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D017077:Culture Media, Conditioned; D003839:Deoxyadenosines; D008070:Lipopolysaccharides; D016328:NF-kappa B; C058120:cordycepin