Thunbergia laurifolia Exhibits Antifibrotic Effects in Human Hepatic Stellate Cells.

Ratchadaporn Namsen,Piyanuch Rojsanga,Noppamas Rojanasthien,Wutigri Nimlamool,Saranyapin Potikanond,Seewaboon Sireeratawong

doi:10.1155/2017/3508569

Abstract

Leaves of Thunbergia laurifolia (TL) have been reported to have antioxidation, anti-inflammatory, detoxifying, and hepatoprotective effects. However, studies relating to antifibrotic activity have not been reported. Currently, there is no standard treatment for hepatic fibrosis. This study aimed to investigate the antifibrotic activity of TL in human hepatic stellate LX-2 cells. Results from cell viability and cell death assays showed that the extract at high concentrations was toxic to LX-2 cells. TL extract reversed the transformation of LX-2 cells to myofibroblast-like characteristics in response to stimulation by transforming growth factor-beta 1. This action may be associated with the effect of TL in suppressing α-SMA and collagen-I production observed by immunofluorescence study and western blot analysis. Additionally, TL extract significantly decreased MMP-9 activity which is consistent with the reduction of MMP-9, MMP-2, and TIMP-1 gene expression. The effect of TL in suppressing fibrosis may be associated with its ability to inhibit the activation of p38 MAPK and Erk1/2 kinases as examined by western blot analysis. Our study provides convincing evidence that TL possesses antifibrotic activity which may be through the suppression of TGF-β1-mediated production of MMPs, collagen-1, and α-SMA in hepatic stellate cells.

Highlights

A consequence of chronic liver inflammation that leads to the activation of hepatic stellate cells (HSCs) is a major cause of hepatic fibrosis [1, 2]
Since we focused mainly on antifibrotic activity of Thunbergia laurifolia (TL), we first evaluated its cytotoxicity to human hepatic stellate cell line (LX-2) by MTT assay
Hepatic fibrosis is a wound-healing response to chronic liver injury characterized by progressive inflammation and deposition of extracellular matrix (ECM) components [30]

Summary

Introduction

A consequence of chronic liver inflammation that leads to the activation of hepatic stellate cells (HSCs) is a major cause of hepatic fibrosis [1, 2]. Liver injury or chronic inflammation results in HSC activation and differentiation into myofibroblast-like cells. These cells have high expression level of α-SMA which has been proved to be a marker in development and progression of fibrosis [7]. TGF-β1 is secreted from activated HSCs and known to be an essential mediator of fibrogenesis [10, 11] It plays crucial roles in many biological processes including cell growth, differentiation, apoptosis, and ECM production [10,11,12]. Besides MMPs, tissue inhibitors of metalloproteinases (TIMPs) can affect the outcome of fibrosis [14]

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