Rosmarinic acid attenuates hepatic fibrogenesis via suppression of hepatic stellate cell activation/proliferation and induction of apoptosis
Date
2017
Authors
M El-Lakkany, Naglaa
H El-Maadawy, Walaa
H Seif el-Din, Sayed
A Hammam, Olfat
H Mohamed, Salwa
Ezzat, Shahira M
M Safar, Marwa
Saleh, Samira
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
sciencedirect
Series Info
Asian Pacific journal of tropical medicine;Volume 10, Issue 5, May 2017, Pages 444-453
Scientific Journal Rankings
Abstract
Objective
To investigate the antifibrotic role of rosmarinic acid (RA), a natural polyphenolic compound, on HSCs activation/proliferation and apoptosis in vitro and in vivo.
Methods
The impact of RA on stellate cell line (HSC-T6) proliferation, activation and apoptosis was assessed along with its safety on primary hepatocytes. In vivo, rats were divided into: (i) normal; (ii) thioacetamide (TAA)-intoxicated rats for 12 weeks; (iii) TAA + silymarin or (iv) TAA + RA. At the end of experiment, liver functions, oxidative stress, inflammatory and profibrogenic markers, tissue inhibitor metalloproteinases type-1 (TIMP-1) and hydroxyproline (HP) levels were evaluated. Additionally, liver histopathology and immunohistochemical examinations of alpha-smooth muscle actin (α-SMA), caspase-3 and proliferation cellular nuclear antigen (PCNA) were determined.
Results
RA exhibited anti-proliferative effects on cultured HSCs in a time and concentration dependent manner showing an IC50 of 276 μg/mL and 171 μg/mL for 24 h and 48 h, respectively, with morphological reversion of activated stellate cell morphology to quiescent form. It significantly improved ALT, AST, oxidative stress markers and reduced TIMP-1, HP levels, inflammatory markers and fibrosis score (S1 vs S4). Furthermore, reduction in α-SMA plus elevation in caspase-3 expressions of HSCs in vitro and in vivo associated with an inhibition in proliferation of damaged hepatocytes were recorded.
Conclusions
RA impeded the progression of liver fibrosis through inhibition of HSCs activation/proliferation and induction of apoptosis with preservation of hepatic architecture.
Description
MSA Google Scholar
Keywords
Hepatic fibrosis, Hepatic stellate cells, Rosmarinic acid, Apoptosis, Proliferation, Profibrogenic markers
Citation
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