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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996
EISSN: 1596-9827
Vol. 14, No. 8, 2015, pp. 1413-1419
Bioline Code: pr15185
Full paper language: English
Document type: Research Article
Document available free of charge

Tropical Journal of Pharmaceutical Research, Vol. 14, No. 8, 2015, pp. 1413-1419

 en Anti-fibrotic Effects of Rhus javanica check for this species in other resources Linn (Anacardiaceae) Extract against Activated Hepatic Stellate Cells via Regulation of TGF-beta and Smad Signaling
Yoo, Seung-Hoon; Yoon, Chan-Jin; Kim, Dong-Ha; Yum, Mun-Jeong; Kim, Jin- Seoub; Yoon, Yeo-Chan; Chun, Chi-Su; Lee, Jae-Dong; Koppula, Sushruta & Song, MinDong

Abstract

Purpose: To evaluate the anti-fibrotic effects of ethanol extract of Rhus javanica check for this species in other resources Linn. (Anacardiaceae) (RJE) in activated hepatic stellate cells (HSCs) as well as explore the underlying mechanisms.
Methods: 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.
Results: 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 signaling pathways.
Conclusion: 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.

Keywords
Liver fibrosis; Rhus javanica; Cytotoxicity; Transforming growth factor-beta; Hepatic stellate cells

 
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