THE EFFECT OF ALPHA-MANGOSTIN ON TRANSFORMING GROWTH FACTOR BETA 1 (TGF-β1) AND MATRIX METALLOPROTEINASE-3 EXPRESSION IN TGF-β-INDUCED HEPATIC STELLATE CELLS
DOI:
https://doi.org/10.22159/ijap.2019.v11s1.16144Keywords:
Alpha-mangostin, Nil, Matrix metalloproteinase-3, Hepatic stellate cellsAbstract
Objective: Alpha-mangostin (α-MG) has been shown to possess antifibrotic effects. However, the specific mechanism of action of this compound
remains poorly understood. Therefore, the aim of this study was to investigate the effect of α-MG on the expression levels of transforming growth
factor (TGF)-β1 and matrix metalloproteinase-3 (MMP3) in hepatic stellate cells (HSCs) induced by TGF-β.
Methods: Immortalized HSCs and LX-2 cells were incubated with TGF-β with or without α-MG (5 and 10 μM). The viability of LX-2 cells was assessed
using the Trypan Blue Exclusion Method. The effect of α-MG on cell morphology and the mRNA expression levels of TGF-β1, TGF-β receptor, and MMP3
was then evaluated.
Results: TGF-β enhanced the proliferation of HSCs and caused significant increases in the expression levels of TGF-β1, TGF-β receptor, and MMP3.
α-MG treatment reduced the proliferation of HSCs and decreased the expression levels of TGF-β1, TGF-β1 receptor, and MMP3.
Conclusion: α-MG is a potential antifibrotic agent due to its antiproliferative and antifibrogenic effects, mainly by suppressing the expression of TGF-β
and MMP3 on the surfaces of activated HSCs.
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2. Mallat A, Lotersztajn S. Cellular mechanisms of tissue fibrosis 5. Novel
insights into liver fibrosis. Am J Physiol Cell Physiol 2013;305:C789?99.
3. Rahmaniah R, Yuyuntia Y, Soetikno V, Arozal W, Antarianto RD,
Louisa M, et al. Alpha mangostin inhibits hepatic stellate cells
activation through TGF-?/Smad and akt signaling pathways: An in vitro
study in LX2. Drug Res (Stuttg) 2018;68:153-8.
4. Li Y, Kim BG, Qian S, Letterio JJ, Fung JJ, Lu L, et al. Hepatic stellate
cells inhibit T cells through active TGF-?1 from a cell surface-bound
latent TGF-?1/GARP complex. J Immunol 2015;195:2648-56.
5. Tin M, Young H, Kim M, Dae DY, Lee H, Cho M. TGF- ?
Secreted from activated hepatic stellate cells may induce the
transdifferentiation of hepatocytes into hepatocarcinoma in
HBx-expressing livers. J Korean Soc Appl Biol Chem 2014;
57:529-38.
6. Kang K, Qian Z, Ryu B, Karadeniz F, Kim D, Kim S. Hepatic fibrosis
inhibitory effect of peptides isolated from navicula incerta on TGF- ?1
induced activation of LX-2 human hepatic stellate cells 2013;18:124?32.
7. Zhang S, Sun W, Wu JJ, Wei W. TGF- ?1signaling pathway as a
pharmacological target in liver diseases. Pharmacol Res 2014;85:15-22.
8. Park JH, Park B, Park KK. Suppression of hepatic epithelial-tomesenchymal
transition by melittin via blocking of TGF?/Smad and
MAPK-JNK signaling pathways. Toxins (Basel) 2017;9:e138.
9. Fagone P, Mangano K, Pesce A, Portale TR, Puleo S, Nicoletti F, et al.
Emerging therapeutic targets for the treatment of hepatic fibrosis. Drug
Discov Today 2016;21:369-75.
10. Giannelli G, Villa E, Lahn M. Transforming growth factor-? as a
therapeutic target in hepatocellular carcinoma. Cancer Res 2014;
74:1890-4.
11. Koyama Y, Brenner DA. New therapies for hepatic fibrosis. Clin Res
Hepatol Gastroenterol 2015;39 Suppl 1:S75-9.
12. Fabregat I, Moreno-Càceres J, Sánchez A, Dooley S, Dewidar B,
Giannelli G, et al. TGF-? signalling and liver disease. FEBS J 2016;
283:2219-32.
13. Dewidar B, Soukupova J, Fabregat I, Dooley S. TGF-? in hepatic
stellate cell activation and liver fibrogenesis: Updated. Curr Pathobiol
Rep 2015;3:291-305.
14. Ibrahim MY, Mariod AA, Mohan S, Hashim M, Abdulla MA,
Abdelwahab SI, et al. ?-Mangostin from Garcinia mangostana Linn:
An updated review of its pharmacological properties. Arab J Chem
2014;9:317-29.
15. Yang Y, Kim B, Park Y, Koo SI, Lee J. Astaxanthin prevents TGF ?
1-induced pro- fi brogenic gene expression by inhibiting Smad3
activation in hepatic stellate cells. Biochimica et Biophysica Acta
2015;1850:178-85.
16. Matharu Z, Patel D, Gao Y, Haque A, Zhou Q, Revzin A, et al.
Detecting transforming growth factor-? release from liver cells using an
aptasensor integrated with microfluidics. Anal Chem 2014;86:8865?72.
17. Tang LY, Heller M, Meng Z, Yu LR, Tang Y, Zhou M, et al. Transforming
growth factor-? (TGF-?) directly activates the JAK1-STAT3 axis to
induce hepatic fibrosis in coordination with the SMAD pathway. J Biol
Chem 2017;292:4302-12.
18. Zhang PF, Li KS, Shen YH, Gao PT, Dong ZR, Cai JB, et al. Galectin-1
induces hepatocellular carcinoma EMT and sorafenib resistance by
activating FAK/PI3K/AKT signaling. Cell Death Dis 2016;7:e2201.
19. Xu F, Liu C, Zhou D, Zhang L. TGF-?/SMAD pathway and its
regulation in hepatic fibrosis. J Histochem Cytochem 2016;64:157-67.
20. Zhao YL, Zhu RT, Sun YL. Epithelial-mesenchymal transition in liver
fibrosis. Biomed Rep 2016;4:269-74.
21. Kim J, An H, Kim W, Gwon M, Gu H, Park Y, et al. Anti-fibrotic effects
of synthetic oligodeoxynucleotide for TGF b 1 and Smad in an animal
model of liver cirrhosis. Mol Ther Nucleic Acid 2017;8:250-63.
22. Yoshida K, Murata M, Yamaguchi T, Matsuzaki K, Okazaki K.
Reversible human TGF-? signal shifting between tumor suppression
and fibro-carcinogenesis: Implications of smad phospho-isoforms for
hepatic epithelial-mesenchymal transitions. J Clin Med 2016;5:e7.
Published
05-04-2019
How to Cite
ADENINA, S., RAHMANIAH, R., YUYUNTIA, Y., SOETIKNO, V., & LOUISA, M. (2019). THE EFFECT OF ALPHA-MANGOSTIN ON TRANSFORMING GROWTH FACTOR BETA 1 (TGF-β1) AND MATRIX METALLOPROTEINASE-3 EXPRESSION IN TGF-β-INDUCED HEPATIC STELLATE CELLS. International Journal of Applied Pharmaceutics, 11(1), 177–180. https://doi.org/10.22159/ijap.2019.v11s1.16144
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