Activation of autophagy is required for Oroxylin A to alleviate carbon tetrachloride-induced liver fibrosis and hepatic stellate cell activation

Activation of autophagy is required for Oroxylin A to alleviate carbon tetrachloride-induced... Liver fibrosis is a reversible pathophysiological process correlated with intense repair and cicatrization mechanisms, and its end-stage cirrhosis is responsible for high morbidity and mortality worldwide. Interestingly, the use of natural products as a realistic option for the treatment of liver fibrosis has broadly been accepted. Oroxylin A, a safe and natural product, shows a wide range of pharmacological activities such as anti-inflammatory, anti-oxidant, and anti-tumor properties. However, the effects of Oroxylin A on liver fibrosis remain poorly understood. In the present study, we sought to determine the effect of Oroxylin A on carbon tetrachloride (CCl4)-induced liver fibrosis, and to further examine the molecular mechanisms. We found that treatment with Oroxylin A markedly decreased the level of liver injury markers, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), in a dose dependent manner. Moreover, Oroxylin A treatment remarkably inhibited extracellular matrix (ECM) deposition, and significantly down-regulated the mRNA and protein expression of liver fibrosis markers including α1(I)collagen, fibronectin, alpha-smooth muscle actin (α-SMA), PDGF-βR, and TGF-βR1 in CCl4-induced murine model of liver fibrosis. Furthermore, experimental results in vitro showed that Oroxylin A treatment reduced the mRNA and protein expression of HSC activation markers, α-SMA, desmin, α1 (I) collagen, fibronectin, TGF-β, and TNF-α, in a dose dependent manner. Attractively, Oroxylin A treatment also markedly up-regulated the expression of autophagy makers, LC3-B, Atg3, Atg4, Atg5, Beclin1/Atg6, Atg7, Atg9, ATG12, and Atg14, and apparently reduced the expression of autophagy substrate p62 in both CCl4-induced murine model of liver fibrosis and PDGF-BB-treated HSCs. Importantly, inhibition of autophagy by specific inhibitor 3-methyladenine (3-MA) completely abolished Oroxylin A-induced anti-fibrosis effect, indicating that activation of autophagy was required for Oroxylin A to alleviate liver fibrosis. Overall, these results provide novel implications to reveal the molecular mechanism of Oroxylin A-induced anti-fibrosis properties, by which points to the possibility of using Oroxylin A for the treatment of liver fibrosis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Immunopharmacology Elsevier

Activation of autophagy is required for Oroxylin A to alleviate carbon tetrachloride-induced liver fibrosis and hepatic stellate cell activation

Loading next page...
 
/lp/elsevier/activation-of-autophagy-is-required-for-oroxylin-a-to-alleviate-carbon-cnPQXuZExh
Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier B.V.
ISSN
1567-5769
eISSN
1878-1705
D.O.I.
10.1016/j.intimp.2018.01.029
Publisher site
See Article on Publisher Site

Abstract

Liver fibrosis is a reversible pathophysiological process correlated with intense repair and cicatrization mechanisms, and its end-stage cirrhosis is responsible for high morbidity and mortality worldwide. Interestingly, the use of natural products as a realistic option for the treatment of liver fibrosis has broadly been accepted. Oroxylin A, a safe and natural product, shows a wide range of pharmacological activities such as anti-inflammatory, anti-oxidant, and anti-tumor properties. However, the effects of Oroxylin A on liver fibrosis remain poorly understood. In the present study, we sought to determine the effect of Oroxylin A on carbon tetrachloride (CCl4)-induced liver fibrosis, and to further examine the molecular mechanisms. We found that treatment with Oroxylin A markedly decreased the level of liver injury markers, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), in a dose dependent manner. Moreover, Oroxylin A treatment remarkably inhibited extracellular matrix (ECM) deposition, and significantly down-regulated the mRNA and protein expression of liver fibrosis markers including α1(I)collagen, fibronectin, alpha-smooth muscle actin (α-SMA), PDGF-βR, and TGF-βR1 in CCl4-induced murine model of liver fibrosis. Furthermore, experimental results in vitro showed that Oroxylin A treatment reduced the mRNA and protein expression of HSC activation markers, α-SMA, desmin, α1 (I) collagen, fibronectin, TGF-β, and TNF-α, in a dose dependent manner. Attractively, Oroxylin A treatment also markedly up-regulated the expression of autophagy makers, LC3-B, Atg3, Atg4, Atg5, Beclin1/Atg6, Atg7, Atg9, ATG12, and Atg14, and apparently reduced the expression of autophagy substrate p62 in both CCl4-induced murine model of liver fibrosis and PDGF-BB-treated HSCs. Importantly, inhibition of autophagy by specific inhibitor 3-methyladenine (3-MA) completely abolished Oroxylin A-induced anti-fibrosis effect, indicating that activation of autophagy was required for Oroxylin A to alleviate liver fibrosis. Overall, these results provide novel implications to reveal the molecular mechanism of Oroxylin A-induced anti-fibrosis properties, by which points to the possibility of using Oroxylin A for the treatment of liver fibrosis.

Journal

International ImmunopharmacologyElsevier

Published: Mar 1, 2018

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve Freelancer

DeepDyve Pro

Price
FREE
$49/month

$360/year
Save searches from
Google Scholar,
PubMed
Create lists to
organize your research
Export lists, citations
Read DeepDyve articles
Abstract access only
Unlimited access to over
18 million full-text articles
Print
20 pages/month
PDF Discount
20% off