Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Anti-fibrotic effects of Rhus javanica Linn (Anacardiaceae) extract against activated hepatic stellate cells via regulation of TGF-beta and smad signaling

Seung-Hoon Yoo¹, Chan-Jin Yoon¹, Dong-Ha Kim^1,4, Mun-Jeong Yum¹, Jin-Seoub Kim¹, Yeo-Chan Yoon², Chi-Su Chun², Jae-Dong Lee³, Sushruta Koppula⁵ , MinDong Song⁵

¹Department of Applied Life Science, Graduate School of Konkuk University, Chungju, Chungbuk; ²Food One Corp, 174-45, Daseseongro, Daeso-myeon, Eumseong-Gun; ³Department of Internal Medicine, School of Medicine, Konkuk University, Chungju, Chungbuk; ⁴Asan Institute of Life Sciences, University of Ulsan College of Medicine, Poongnap-Dong, Songpa-Gu, Seoul; ⁵Department of Biotechnology, College of Biomedical and Health Sciences, Konkuk University, Chungju, Chungbuk, 380-701, South Korea.

For correspondence:- Sushruta Koppula Email: minds@kku.ac.kr Tel:+82-438403612

Received: 14 April 2015 Accepted: 7 July 2015 Published: 30 August 2015

Citation: Yoo S, Yoon C, Kim D, Yum M, Kim J, Yoon Y, et al. Anti-fibrotic effects of Rhus javanica Linn (Anacardiaceae) extract against activated hepatic stellate cells via regulation of TGF-beta and smad signaling. Trop J Pharm Res 2015; 14(8):1413-1419 doi: 10.4314/tjpr.v14i8.13

© 2015 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To evaluate the anti-fibrotic effects of ethanol extract of Rhus javanica 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