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Alpha Mangostin Inhibits the Proliferation and Activation of Acetaldehyde Induced Hepatic Stellate Cells through TGF-β and ERK 1/2 Pathways
Liver fibrosis is characterized by excessive accumulation of extracellular matrix in chronic liver injury. Alcohol-induced fibrosis 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 pA...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261236/ https://www.ncbi.nlm.nih.gov/pubmed/30538742 http://dx.doi.org/10.1155/2018/5360496 |
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author | Lestari, Novriantika Louisa, Melva Soetikno, Vivian Suwana, Averina Geffanie Ramadhan, Putra Andito Akmal, Taufiq Arozal, Wawaimuli |
author_facet | Lestari, Novriantika Louisa, Melva Soetikno, Vivian Suwana, Averina Geffanie Ramadhan, Putra Andito Akmal, Taufiq Arozal, Wawaimuli |
author_sort | Lestari, Novriantika |
collection | PubMed |
description | Liver fibrosis is characterized by excessive accumulation of extracellular matrix in chronic liver injury. Alcohol-induced fibrosis 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-β-induced liver fibrosis model in vitro. Further investigation of the mechanism of action of alpha mangostin in liver fibrosis model still needs to be done. The present study aimed to analyze the mechanism of action of alpha mangostin on acetaldehyde induced liver fibrosis model on TGF-β and ERK 1/2 pathways. Immortalized HSCs, LX-2 cells, were incubated with acetaldehyde, acetaldehyde with alpha mangostin (10 and 20 μM), or alpha mangostin only (10 μM). Sorafenib 10 μM was used as positive control. LX-2 viability was counted using trypan blue exclusion method. The effect of alpha mangostin on hepatic stellate cells proliferation and activation markers and its possible mechanism of action via TGF-β and ERK1/2 were studied. Acetaldehyde was shown to increase proliferation and expression of profibrogenic 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. These findings were followed with decreased expressions and concentrations of TGF-β; decreased expression of Col1A1, TIMP1, and TIMP3; increased expression of MnSOD and GPx; and reduction in intracellular reactive oxygen species. These effects were shown to be dose dependent. Therefore, we conclude that alpha mangostin inhibits hepatic stellate cells proliferation and activation through TGF-β and ERK 1/2 pathways. |
format | Online Article Text |
id | pubmed-6261236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-62612362018-12-11 Alpha Mangostin Inhibits the Proliferation and Activation of Acetaldehyde Induced Hepatic Stellate Cells through TGF-β and ERK 1/2 Pathways Lestari, Novriantika Louisa, Melva Soetikno, Vivian Suwana, Averina Geffanie Ramadhan, Putra Andito Akmal, Taufiq Arozal, Wawaimuli J Toxicol Research Article Liver fibrosis is characterized by excessive accumulation of extracellular matrix in chronic liver injury. Alcohol-induced fibrosis 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-β-induced liver fibrosis model in vitro. Further investigation of the mechanism of action of alpha mangostin in liver fibrosis model still needs to be done. The present study aimed to analyze the mechanism of action of alpha mangostin on acetaldehyde induced liver fibrosis model on TGF-β and ERK 1/2 pathways. Immortalized HSCs, LX-2 cells, were incubated with acetaldehyde, acetaldehyde with alpha mangostin (10 and 20 μM), or alpha mangostin only (10 μM). Sorafenib 10 μM was used as positive control. LX-2 viability was counted using trypan blue exclusion method. The effect of alpha mangostin on hepatic stellate cells proliferation and activation markers and its possible mechanism of action via TGF-β and ERK1/2 were studied. Acetaldehyde was shown to increase proliferation and expression of profibrogenic 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. These findings were followed with decreased expressions and concentrations of TGF-β; decreased expression of Col1A1, TIMP1, and TIMP3; increased expression of MnSOD and GPx; and reduction in intracellular reactive oxygen species. These effects were shown to be dose dependent. Therefore, we conclude that alpha mangostin inhibits hepatic stellate cells proliferation and activation through TGF-β and ERK 1/2 pathways. Hindawi 2018-11-14 /pmc/articles/PMC6261236/ /pubmed/30538742 http://dx.doi.org/10.1155/2018/5360496 Text en Copyright © 2018 Novriantika Lestari et al. https://creativecommons.org/licenses/by/4.0/ This 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. |
spellingShingle | Research Article Lestari, Novriantika Louisa, Melva Soetikno, Vivian Suwana, Averina Geffanie Ramadhan, Putra Andito Akmal, Taufiq Arozal, Wawaimuli Alpha Mangostin Inhibits the Proliferation and Activation of Acetaldehyde Induced Hepatic Stellate Cells through TGF-β and ERK 1/2 Pathways |
title | Alpha Mangostin Inhibits the Proliferation and Activation of Acetaldehyde Induced Hepatic Stellate Cells through TGF-β and ERK 1/2 Pathways |
title_full | Alpha Mangostin Inhibits the Proliferation and Activation of Acetaldehyde Induced Hepatic Stellate Cells through TGF-β and ERK 1/2 Pathways |
title_fullStr | Alpha Mangostin Inhibits the Proliferation and Activation of Acetaldehyde Induced Hepatic Stellate Cells through TGF-β and ERK 1/2 Pathways |
title_full_unstemmed | Alpha Mangostin Inhibits the Proliferation and Activation of Acetaldehyde Induced Hepatic Stellate Cells through TGF-β and ERK 1/2 Pathways |
title_short | Alpha Mangostin Inhibits the Proliferation and Activation of Acetaldehyde Induced Hepatic Stellate Cells through TGF-β and ERK 1/2 Pathways |
title_sort | alpha mangostin inhibits the proliferation and activation of acetaldehyde induced hepatic stellate cells through tgf-β and erk 1/2 pathways |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261236/ https://www.ncbi.nlm.nih.gov/pubmed/30538742 http://dx.doi.org/10.1155/2018/5360496 |
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