ANTIOXIDATIVE ACTIVITY OF ALPHA-MANGOSTIN IN ACETALDEHYDE-INDUCED HEPATIC STELLATE CELLS: AN IN VITRO STUDY

NOVRIANTIKA LESTARI; SAMUEL PRATAMA; KELVIN THEANDRO GOTAMA; VIVIAN SOETIKNO; MELVA LOUISA

doi:10.22159/ijap.2019.v11s1.16089

Authors

NOVRIANTIKA LESTARI Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia,
SAMUEL PRATAMA Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia,
KELVIN THEANDRO GOTAMA Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia,
VIVIAN SOETIKNO Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia.
MELVA LOUISA Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia.

DOI:

https://doi.org/10.22159/ijap.2019.v11s1.16089

Keywords:

Acetaldehyde, Alpha-mangostin, Antioxidant

Abstract

Objective: Alcohol accumulation in the liver can cause pathological disorders such as liver fibrosis that can develop into hepatocellular carcinoma,
one of the main causes of mortality associated with liver disease. The previous studies have shown that a plant compound, alpha-mangostin, has an
antioxidant effect in the inhibition of pancreatic tumor growth in vitro. This study aimed to analyze the antioxidative properties of alpha-mangostin in
acetaldehyde-induced liver fibrosis in vitro.
Methods: Immortalized hepatic stellate cells (HSCs), of the LX-2 cell line, were incubated with acetaldehyde in the presence or absence of alphamangostin
(10 and 20 μM). The cells were then counted and lysed, and LX-2 cell viability was determined with the trypan blue exclusion method. The
malondialdehyde levels, superoxide dismutase activity, and glutathione (GSH) levels were also determined using the cell lysates.
Results: Acetaldehyde treatment resulted in a significant increase in HSC cell viability and decreased the production of GSH. Alpha-mangostin
treatment resulted in reduced cell viability of the HSCs and prevention of the loss of intracellular GSH.
Conclusion: Alpha-mangostin reduced acetaldehyde-induced cell proliferation, and this was affected at least in part by its antioxidative properties

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References

1. Chrostek L, Panasiuk A. Liver fibrosis markers in alcoholic liver
disease. World J Gastroenterol 2014;20:8018-23.
2. Sidharthan S, Kottilil S. Mechanisms of alcohol-induced hepatocellular
carcinoma. Hepatol Int 2014;8:452-7.
3. Hernandez-Gea V, Friedman SL. Pathogenesis of liver fibrosis. Annu
Rev Pathol Mech Dis 2011;6:425-56.
4. Koyama Y, Brenner DA. New therapies for hepatic fibrosis. Clin Res
Hepatol Gastroenterol 2015;39 Suppl 1:S75-9.
5. Li JT, Liao ZX, Ping J, Xu D, Wang H. Molecular mechanism of
hepatic stellate cell activation and antifibrotic therapeutic strategies.
J Gastroenterol 2008;43:419-28.
6. Wang JH, Batey RG, George J. Role of ethanol in the regulation of
hepatic stellate cell function. World J Gastroenterol 2006;12:6926-32.
7. Setshedi M, Wands JR, de la Monte SM. Acetaldehyde adducts in
alcoholic liver disease. Oxid Med Cell Longev 2010;3:178-85.
8. Liu R-M, Desai LP. Reciprocal regulation of TGF-? and reactive oxygen
species: A perverse cycle for fibrosis. Redox Biol 2015;6:565-77.
9. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen
species in inflammation and tissue injury. Antioxid Redox Signal
2014;20:1126-67.
10. Ibrahim MY, Hashim NM, Mariod AA, Mohan S, Abdulla MA,
Abdelwahab SI, et al. ?-mangostin from Garcinia mangostana Linn:
An updated review of its pharmacological properties. Arab J Chem
2016;9:317-29.
11. Lee LT, Liu SH, Lin MN, Hu NY, Tsai YF, Shih YC, et al. Effects of
mangosteen on ?-SMA expression in HSC-T6 cells and liver fibrosis in
rats. J Chin Med 2013;24:211-22.
12. Rahmaniah R, Yuyuntia Y, Soetikno V, Arozal W, Antarianto R,
Louisa M. Alpha mangostin inhibits hepatic stellate cells activation
through TGF-?/Smad and Akt signaling pathways: An in vitro study in
LX2. Drug Res 2018;68:153-8.
13. Siddique YH, Ara G, Afzal M. Estimation of lipid peroxidation induced
by hydrogen peroxide in cultured human lymphocytes. Dose Response
2012;10:1-0.
14. Misra HP, Fridovich I. The role of superoxide anion in the autooxidation
of epinephrine and a simple assay for superoxide dismutase. J Biol
Chem 1972;247:3170-5.
15. Wang H, Guan W, Yang W, Wang Q, Zhao H, Yang F, et al. Caffeine
inhibits the activation of hepatic stellate cells induced by acetaldehyde
via adenosine A2A receptor mediated by the cAMP/PKA/SRC/
ERK1/2/P38 MAPK signal pathway. PLoS One 2014;9:e92482.
16. Zhang QS, Luk JM, Zhang J, Tian GY. Targeting glycyrrhetinic acid to
hepatic stellate cells in treating rat liver fibrosis. Zhonghua Gan Zang
Bing Za Zhi 2005;13:664-7.
17. Yan T, Zhao Y, Zhang X. Acetaldehyde induces cytotoxicity of SHSY5Y
cells via inhibition of akt activation and induction of oxidative
stress. Oxid Med Cell Longev 2016;2016:4512309.
18. Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: Production,
metabolism, and signaling mechanisms of malondialdehyde and
4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014;2014:360438.
19. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative
stress and antioxidant defense. World Allergy Organ J 2012;5:9-19.
20. Han KH, Hashimoto N, Fukushima M. Relationships among alcoholic
liver disease, antioxidants, and antioxidant enzymes. World J
Gastroenterol 2016;22:37-49.