IMR Press / FBL / Volume 25 / Issue 5 / DOI: 10.2741/4835

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Amentoflavone induces cell cycle arrest, apoptosis, and autophagy in BV-2 cells
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1 Department of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China
2 Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan 750004, Ningxia, China
Front. Biosci. (Landmark Ed) 2020, 25(5), 798–816; https://doi.org/10.2741/4835
Published: 1 January 2020
(This article belongs to the Special Issue Leader sequences of coronavirus are altered during infection)
Abstract

Previous studies have shown that amentoflavone (AF) elicits anti-inflammatory and neuroprotective effects. To further investigate the effects of AF on the microglia cell line BV-2, proteomic analysis was performed to screen potential key regulators. The top 5 canonical pathways associated with AF treatment were EIF2 signaling, regulation of eIF4 and p70s6k signaling, mTOR signaling, protein ubiquitination pathway and phagosome maturation. The top up-regulated genes were DOCK2, SEC23A, ME1, UGGT1 and STOM, while the most down-regulated molecules were IGF2R, ATP5O, DDX47, WBP11 and IKBIP. AF significantly decreased BV-2 cell proliferation. It induced cell cycle arrest at G2/M, increased CDK2, p27Kip1 and p53/p-p53, and decreased CDK1/CDC2 and cyclin B1. Cell apoptosis was induced, with increased levels of BAX, c-caspase-3 and c-caspase-9, and decreased levels of BCL-XL. Increased level of autophagosome induced by AF was observed, and increased Beclin-1 and decreased phosphorylation of PI3K and Erk1 were found as well. In conclusion, AF induces cell cycle arrest at G2/M, promotes apoptosis and autophagy in BV-2 cells, which may account for the anti-inflammatory effect of AF in epilepsy.

Keywords
Epilepsy
Amentoflavone
BV-2 cells
Apoptosis
Cell cycle arrest
Autophagy
Figures
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