Research Article Alpha Mangostin Inhibits the Proliferation and Activation of Acetaldehyde Induced Hepatic Stellate Cells through TGF- and ERK 1/2 Pathways Novriantika Lestari, 1,2 Melva Louisa , 3 Vivian Soetikno, 3 Averina Geffanie Suwana, 4 Putra Andito Ramadhan, 4 Taufiq Akmal, 4 and Wawaimuli Arozal 3 1 Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Indonesia 2 Department of Pharmacology, Faculty of Medicine and Health Sciences, University of Bengkulu, Indonesia 3 Department of Pharmacology and erapeutics, Faculty of Medicine, Universitas Indonesia, Indonesia 4 Faculty of Medicine, Universitas Indonesia, Indonesia Correspondence should be addressed to Melva Louisa; melva.louisa@gmail.com Received 31 May 2018; Revised 7 October 2018; Accepted 24 October 2018; Published 14 November 2018 Academic Editor: Anthony DeCaprio Copyright © 2018 Novriantika Lestari et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Liver fbrosis is characterized by excessive accumulation of extracellular matrix in chronic liver injury. Alcohol-induced fbrosis may develop into cirrhosis, one of the major causes of liver disease mortality. Previous studies have shown that alpha mangostin can decrease ratio of pSmad/Smad and pAkt/Akt in TGF--induced liver fbrosis model in vitro. Further investigation of the mechanism of action of alpha mangostin in liver fbrosis model still needs to be done. Te present study aimed to analyze the mechanism of action of alpha mangostin on acetaldehyde induced liver fbrosis model on TGF- and ERK 1/2 pathways. Immortalized HSCs, LX- 2 cells, were incubated with acetaldehyde, acetaldehyde with alpha mangostin (10 and 20 M), or alpha mangostin only (10 M). Sorafenib 10 M was used as positive control. LX-2 viability was counted using trypan blue exclusion method. Te efect of alpha mangostin on hepatic stellate cells proliferation and activation markers and its possible mechanism of action via TGF- and ERK1/2 were studied. Acetaldehyde was shown to increase proliferation and expression of profbrogenic and migration markers on HSC, while alpha mangostin treatment resulted in a reduced proliferation and migration of HSC and decreased Ki-67 and pERK 1/2 expressions. Tese fndings were followed with decreased expressions and concentrations of TGF-; decreased expression of Col1A1, TIMP1, and TIMP3; increased expression of MnSOD and GPx; and reduction in intracellular reactive oxygen species. Tese efects were shown to be dose dependent. Terefore, we conclude that alpha mangostin inhibits hepatic stellate cells proliferation and activation through TGF- and ERK 1/2 pathways. 1. Introduction Liver fbrosis is characterized by excessive accumulation of extracellular matrix including collagen tissue in chronic liver injury [1]. Liver fbrosis can be caused partly due to chronic infection of hepatitis C virus, alcohol consumption, and nonalcoholic steatohepatitis (NASH). Cirrhosis due to alcohol consumption is one of the major causes of morbidity and mortality associated with liver disease [2, 3]. Hepatic stellate cells (HSCs) play an important role as a central component in the fbrosis process induced by alcohol consumption. In normal liver, HSC is a qui- escent and serves as a retinoid deposit that will diferen- tiate into myofbroblasts when activated [4, 5]. Te stim- ulus of HSC activation may be derived from paracrine stimulation by hepatocyte cells, Kupfer cells, and injured endothelial cells. In active HSCs, the synthesis of endoge- nous TGF- increases signifcantly. Te results of alcohol metabolism also increase the production of TGF-. Conse- quently, TGF- synergizes with alcohol in inducing oxidative stress, thus increasing alcohol-induced liver damage [6– 8]. Hindawi Journal of Toxicology Volume 2018, Article ID 5360496, 9 pages https://doi.org/10.1155/2018/5360496