Physalin D attenuates hepatic stellate cell activation and liver fibrosis by blocking TGF-β/Smad and YAP signaling.
Actins
/ metabolism
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Carbon Tetrachloride
/ toxicity
Cells, Cultured
Collagen Type I
/ genetics
Collagen Type I, alpha 1 Chain
Hepatic Stellate Cells
/ drug effects
Humans
Liver Cirrhosis
/ drug therapy
Male
Mice, Inbred C57BL
Secosteroids
/ pharmacology
Signal Transduction
/ drug effects
Smad Proteins
/ metabolism
Transcription Factors
/ genetics
Transforming Growth Factor beta
/ metabolism
Transforming Growth Factor beta1
YAP-Signaling Proteins
HSC activation
Liver fibrosis
PD
TGF-β1/Smad
YAP
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
28
01
2020
revised:
14
06
2020
accepted:
24
07
2020
pubmed:
11
8
2020
medline:
1
12
2020
entrez:
11
8
2020
Statut:
ppublish
Résumé
Hepatic fibrosis is considered integral to the progression of chronic liver diseases, as it leads to the development of cirrhosis and hepatocellular carcinoma. The activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. The transforming growth factor-β1 (TGF-β1) and Yes-associated protein (YAP) pathways play a pivotal role in HSC activation, hepatic fibrosis and cirrhosis progression. Therefore, targeting the TGF-β/Smad and YAP signaling pathways is a promising strategy for antifibrotic therapy. The present study investigated the protective effects of Physalin D (PD), a withanolide isolated from Physalis species (Solanaceae), against liver fibrosis and further elucidated the mechanisms involved in vitro and in vivo. We conducted a series of experiments using carbon tetrachloride (CCl PD decreased TGF-β1-induced COL1A1 promoter activity. PD inhibited TGF-β1-induced expression of Collagen I and α-smooth muscle actin (α-SMA) in human hepatic stellate LX-2 cells. PD significantly ameliorated hepatic injury, including transaminase activities, histology, collagen deposition and α-SMA, in CCl These results clearly show that PD ameliorated experimental liver fibrosis by inhibiting the TGF-β/Smad and YAP signaling pathways, indicating that PD has the potential to effectively treat liver fibrosis.
Sections du résumé
BACKGROUND
BACKGROUND
Hepatic fibrosis is considered integral to the progression of chronic liver diseases, as it leads to the development of cirrhosis and hepatocellular carcinoma. The activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. The transforming growth factor-β1 (TGF-β1) and Yes-associated protein (YAP) pathways play a pivotal role in HSC activation, hepatic fibrosis and cirrhosis progression. Therefore, targeting the TGF-β/Smad and YAP signaling pathways is a promising strategy for antifibrotic therapy.
PURPOSE
OBJECTIVE
The present study investigated the protective effects of Physalin D (PD), a withanolide isolated from Physalis species (Solanaceae), against liver fibrosis and further elucidated the mechanisms involved in vitro and in vivo.
STUDY DESIGN/METHODS
METHODS
We conducted a series of experiments using carbon tetrachloride (CCl
RESULT
RESULTS
PD decreased TGF-β1-induced COL1A1 promoter activity. PD inhibited TGF-β1-induced expression of Collagen I and α-smooth muscle actin (α-SMA) in human hepatic stellate LX-2 cells. PD significantly ameliorated hepatic injury, including transaminase activities, histology, collagen deposition and α-SMA, in CCl
CONCLUSION
CONCLUSIONS
These results clearly show that PD ameliorated experimental liver fibrosis by inhibiting the TGF-β/Smad and YAP signaling pathways, indicating that PD has the potential to effectively treat liver fibrosis.
Identifiants
pubmed: 32771890
pii: S0944-7113(20)30126-4
doi: 10.1016/j.phymed.2020.153294
pii:
doi:
Substances chimiques
ACTA2 protein, human
0
Actins
0
Adaptor Proteins, Signal Transducing
0
Collagen Type I
0
Collagen Type I, alpha 1 Chain
0
Secosteroids
0
Smad Proteins
0
TGFB1 protein, human
0
Transcription Factors
0
Transforming Growth Factor beta
0
Transforming Growth Factor beta1
0
YAP-Signaling Proteins
0
YAP1 protein, human
0
physalin D
0
Carbon Tetrachloride
CL2T97X0V0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
153294Informations de copyright
Copyright © 2020 Elsevier GmbH. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest No potential conflicts of interest were disclosed.