Coeloglossum viride var. bracteatum extract attenuates staurosporine induced neurotoxicity by restoring the FGF2-PI3K/Akt signaling axis and Dnmt3

Abstract

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.

Coeloglossum viride Var. Bracteatum Extract Attenuates MPTP-Induced Neurotoxicity in vivo by Restoring BDNF-TrkB and FGF2-Akt Signaling Axis and Inhibiting RIP1-Driven Inflammation

“…bracteatum was identified, collected, and processed as previously described ( Huang et al, 2004 ; Shang et al, 2017 ; Li et al, 2022 ). In this work, CE was prepared and its chemical composition was characterized according to previous methods ( Cai et al, 2021 ; Li et al, 2021 ). In brief, the dried tubers of Coeloglossum viride var.…”

“…The n-butanol extract was furthered purified by passing through a HP-20 macroporous resin. The final product used in this study was characterized by a hydrosphere C18 column for the main components of CE, including Dactylorhin A, Dactylorhin B, Loroglossin, and Militarine ( Cai et al, 2021 ). Madopar is a clinical anti-PD drug containing two active ingredients, levodopa (#S2176, Selleck) and benserazide (#S2453, Selleck) in a ratio of 4:1.…”

“…bracteatum extract (CE) as the main ingredient, such as “Shi Wei Shou Shen San”, “Fu Fang Shou Shen Wan”, have been approved by the State Medical Products Administration of China ( https://www.nmpa.gov.cn ) and are listed in the Chinese Pharmacopeia. We have previously identified the composition of CE and demonstrated its neuroprotective effects in AlCl 3 /Gal-induced cognitive impairment or 5xFAD Alzheimer’s disease mouse models ( Zhong et al, 2019 ; Cai et al, 2021 ; Li et al, 2021 ). CE exerts a large number of antioxidant, anti-aging and anti-inflammatory properties and has no auto-toxicity, thus a potential drug for the treatment of neurodegenerative diseases ( Shang et al, 2017 ).…”