To evaluate the anti-fibrotic effects of ethanol extract of Rhus javanica
(RJE) in activated hepatic stellate cells (HSCs) as well as explore the underlying mechanisms.
The cytotoxic effect of RJE (100, 300 and 500 μg/mL) was analyzed using 3-[4, 5-
dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay in Chang liver cells. The mRNA
expression of collagen type I, alpha 2 (COL1A2), transforming growth factor-beta (TGF-β), α-smooth
muscle actin (α-SMA) and platelet-derived growth factor (PDGF) were determined using reverse
transcription-polymerase chain reaction (RT-PCR) in HSCs. Protein expression of collagen and Smad
were measured by Western blot analysis.
Treatment with RJE extract at 100, 300 and 500 μg/mL did not show any signs of cytotoxicity
to Chang liver cells. RJE at 500 μg/mL concentration influenced the morphology, reduced the stretched
fiber and decreased the number of viable cells in activated HSCs. The increased expressional levels of
fibrosis mediators such as COL1A2, TGF-β, α-SMA were decreased by RJE (500 μg/mL) pre-treatment.
Quantification data showed that the increased band intensity of COL1A2 (1.41 ± 0.08), TGF-β (1.23 ±
0.13), α-SMA (1.71 ± 0.14) were significantly (p < 0.05) reduced to 0.39 ± 0.12, 0.35 ± 0.11 and 0.04 ±
0.08, respectively upon RJE treatment. However, RJE did not suppress the expression of PDGF gene.
Mechanistic study revealed that RJE prevented fibrosis in HSCs via regulation of TGF-β and Smad
The findings show that RJE inhibits fibrosis production in HSCs and can be developed as
a novel therapy for hepatic fibrosis. This is the first report showing the beneficial effects of R. javanica
as an anti-fibrotic agent.