Study of anti-liver fibrosis effects and molecular mechanisms of oolong tea polyphenol theasinensin A in vivo and in vitro
Date Issued
2016
Date
2016
Author(s)
Wang, Yu-Chuan
Abstract
Liver fibrosis is a pathological scarring process in response to a variety of chronic stimuli. It leads to the development of severe complications including liver failure, liver cirrhosis and hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs) are the predominant cell type in the development of liver fibrosis. Following liver injury, HSCs are activated and transformed into a myofibroblast-like phenotype, characterized by the accumulation of stress fibres, such as α-smooth muscle actin (α-SMA), increased production of extracellular matrix (ECM) proteins, decreased matrix degradation. Oolong tea is consumed heavily in Asian and most Eastern countries. Oolong tea theasinensins are a group of tea polyphenols, and they are considered as bioactive compounds in Oolong tea. Among five types of theasinensins, theasinensin A (TSA) is the major theasinensins in oolong tea. Several studies have revealed that TSA have potential biological activities, such as antioxidative effects, apoptosis induction, inhibitory effect on MMPs activities and anti-inflammatory activities. Because chromatographic separation of tea polyphenols is too difficult to supply sufficient quantities of pure compounds for biological experiments, I decided to use biomimetic preparation of TSA. And we evaluated its anti-liver fibrosis effects in vivo and in vitro. In in vivo experiments, I used 6-week-old male ICR mice as animal model and gave them 40% CCl4/olive oil by I.P. injection to induce them liver fibrosis. The results revealed that TSA can ameliorate liver injury compared with CCl4+H2O group. Also, TSA can restrain the progression of liver fibrosis due to the down-regulation of α-SMA and collagen depositing in liver tissue. Meanwhile, TSA can inhibit the expression levels of TIMP-1 and MMP-9 which are both important markers of activated HSCs and liver fibrosis. The results of in vitro experiments showed that the expression levels of TIMP-1, MMP-2 and MMP-9 were decreased because TSA inhibited TGF-β1/Smad2/3 signaling pathway. Thus the activation and migrated ability of HSC-T6 cells were inhibited. In conclusion, TSA has the effects on retarding the progression of liver fibrosis.
Subjects
liver fibrosis
Hepatic stellate cells (HSCs)
Oolong tea theasinensins
theasinensin A (TSA)
Matrix metalloproteinases (MMPs)
CCl4-induced liver fibrosis
Type
thesis