ReferenceID 4883

Cepharanthine Suppresses Herpes Simplex Virus Type 1 Replication Through the Downregulation of the PI3K/Akt and p38 MAPK Signaling Pathways

Front Microbiol

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 promisin

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Reference Id
4883
Evidence Id
21473
Core Evidence Id
21473
Source Reference Id
3015
Herb2 Reference Id
HBREF003812
Subject Paper Key
HBIN020124_34956164
Pubmed Id
34956164
Doi
10.3389/fmicb.2021.795756
Paper Title
Cepharanthine Suppresses Herpes Simplex Virus Type 1 Replication Through the Downregulation of the PI3K/Akt and p38 MAPK Signaling Pathways
Paper Abstract
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 IkappaB kinasealpha (IkappaBalpha). 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.
Journal
Front Microbiol
Publish Year
2021
Experiment Subject
g2/m phase cells
Experiment Type
Cell Experiment
Phenotype Related
Hsv-1 Infection
Paper Title Cn
Paper Title En
Cepharanthine Suppresses Herpes Simplex Virus Type 1 Replication Through the Downregulation of the PI3K/Akt and p38 MAPK Signaling Pathways
Bilingual Status
semi_complete