Coeloglossum viride var. bracteatum extract attenuates staurosporine induced neurotoxicity by restoring the FGF2-PI3K/Akt signaling axis and Dnmt3
Zhe-Ping Cai,
Chang Cao,
Zhe Guo,
Yun Yu,
Si-Jia Zhong,
Rui-Yuan Pan,
Haowen Liang,
Rongfeng Lan,
Xiao-Yan Qin
Affiliations
Zhe-Ping Cai
Key Laboratory of Ecology and Environment in Minority Areas, National Ethnic Affairs Commission, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China
Chang Cao
Key Laboratory of Ecology and Environment in Minority Areas, National Ethnic Affairs Commission, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China
Zhe Guo
The Emergency Department, The Third Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China
Yun Yu
Key Laboratory of Ecology and Environment in Minority Areas, National Ethnic Affairs Commission, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China
Si-Jia Zhong
College of Economics and Management, North China Electric Power University, Beijing, 102206, China
Rui-Yuan Pan
Key Laboratory of Ecology and Environment in Minority Areas, National Ethnic Affairs Commission, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China
Haowen Liang
College of Letters & Science, University of California Los Angeles, CA, 90024, USA
Rongfeng Lan
Department of Cell Biology & Medical Genetics, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, 518060, China; Corresponding author.
Xiao-Yan Qin
Key Laboratory of Ecology and Environment in Minority Areas, National Ethnic Affairs Commission, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China; Corresponding author.
We previously demonstrated the antioxidant activity of Coeloglossum viride var. bracteatum extract (CE) in rat cortical neurons and in mice with chemically induced cognitive impairment. In this work, we established a staurosporine (STS)-induced toxicity model to decipher the neuroprotective mechanisms of CE. We found that CE protected cell viability and neurite integrity in STS-induced toxicity by restoring the levels of FGF2 and its associated PI3K/Akt signaling axis. LY294002, a pan-inhibitor of PI3K, antagonized the activity of CE, although its-mediated restoration of FGF2 was unaffected. In addition, CE restored levels of Bcl-2/Caspase-3, PKCα/CaM pathway, and Dnmt3a and Dnmt3b, two methyltransferases that contribute to de novo DNA methylation. The Dnmts inhibitor 5-azacytidine impaired CE-mediated restoration of Dnmt3 or CaM, as well as the transition of DNA methylation status on the Dnmt3 promoter. These results reveal potential mechanisms that could facilitate the study and application of CE as a neuroprotective agent.
