Antifibrosis Effect of Novel Oridonin Analog CYD0618 Via Suppression of the NF-κB Pathway.
J Surg Res
; 232: 283-292, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30463731
ABSTRACT
BACKGROUND:
Liver fibrosis is characterized as excessive deposition of the extracellular matrix proteins, primarily by activated hepatic stellate cells (HSCs). NF-κB has been reported as one of the major mediators of HSC activation. Previously, our team reported that oridonin exhibited antihepatic fibrogenetic activity in vitro. In this study, we examined the effects of its novel derivative CYD0618 on HSC viability, apoptosis, and NF-κB signaling.METHODS:
Cell proliferation of activated human and rat HSC lines LX-2 and HSC-T6 was measured using Alamar Blue Assay. Apoptosis was measured by a Cell Death Detection ELISA kit. Cellular proteins were determined by Western blots and immunofluorescence.RESULTS:
CYD0618 significantly inhibited LX-2 and HSC-T6 cell proliferation in a dose-dependent manner. CYD0618 induced cell apoptosis in both cell lines. CYD0618 treatment increased cell cycle inhibitory protein p21, p27, and induced apoptosis marker cleaved poly (ADP-ribose) polymerase, while suppressing the expression of Collagen type 1. CYD0618 blocked lipopolysaccharide (LPS)-induced NF-κB p65 nuclear translocation and DNA binding activity and prevented LPS-induced NF-κB inhibitory protein IκBα phosphorylation and degradation. LPS-stimulated NF-κB downstream target cytokines IL-6 and MCP-1 were attenuated by CYD0618. Endogenous and LPS-stimulated NF-κB p65 S536 phosphorylation was inhibited by CYD0618 treatment.CONCLUSIONS:
The potent antihepatic fibrogenetic effect of CYD0618 may be mediated via suppression of the NF-κB pathway.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiazóis
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Transdução de Sinais
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NF-kappa B
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Diterpenos do Tipo Caurano
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Cirrose Hepática
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Surg Res
Ano de publicação:
2018
Tipo de documento:
Article