Autor: |
Yao Liu, Li Chen, Wenjun Liu, Dan Li, Jiuseng Zeng, Qiong Tang, Yuexin Zhang, Fei Luan, Nan Zeng |
Jazyk: |
angličtina |
Rok vydání: |
2021 |
Předmět: |
|
Zdroj: |
Frontiers in Microbiology, Vol 12 (2021) |
Druh dokumentu: |
article |
ISSN: |
1664-302X |
DOI: |
10.3389/fmicb.2021.795756 |
Popis: |
Cepharanthine (CEP) is a naturally occurring isoquinoline alkaloid extracted from Stephania cepharantha Hayata. Although its underlying molecular mechanism is not fully understood, this compound is reported as a promising antiviral drug. In the present study, we explore the anti-HSV-1 effects and the underlying molecular mechanisms of CEP in vitro. Our results show that CEP could significantly inhibit the formation of plaque and the expression of viral proteins and exhibit a general suppression of replication-associated genes. Whereas HSV-1 infection increases the expressions of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and p38 mitogen-activated protein kinase (p38 MAPK) in host cells, CEP was effective indirectly inhibiting phosphorylation levels of the targets in PI3K/Akt and p38 MAPK signaling pathways. Moreover, CEP markedly decreased G0/G1 phase and increased G2/M phase cells and decreased the expression of cyclin-dependent kinase1 (CDK1) and cyclinB1 in a dose-dependent manner. Additionally, CEP increased apoptosis in infected cells, reduced B cell lymphoma-2 (Bcl-2) protein levels, and increased the protein levels of Bcl-associated X protein (Bax), cleaved-caspase3, and nuclear IκB kinaseα (IκBα). Collectively, CEP could arrest the cell cycle in the G2/M phase and induce apoptosis in infected cells by inhibiting the PI3K/Akt and p38 MAPK signaling pathways, hence further reducing HSV-1 infection and subsequent reproduction. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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