Standardized bioactive fraction of Phaleria macrocarpa (Proliverenol) prevents ethanol-induced hepatotoxicity via down-regulation of NF-κB-TNFα-caspase-8 pathway

Objective: To verify that Proliverenol has a potential ability in protecting cells from ethanol-induced hepatotoxicity. Methods: Activity of Proliverenol against ethanol-induced apoptosis was evaluated at mRNA and protein levels in HepG2 cell exposed to Proliverenol for 1 and 3 h. Results: Prolivere...

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Bibliographic Details
Published in:Asian Pacific Journal of Tropical Biomedicine
Main Authors: Guntur Berlian, Olivia Mayasari Tandrasasmita, Raymond Rubianto Tjandrawinata
Format: Article in Journal/Newspaper
Language:English
Published: Wolters Kluwer Medknow Publications 2016
Subjects:
Phaleria macrocarpa
Hepatoprotector
Liver injury
Cirrhosis
HepG2
Arctic medicine. Tropical medicine
RC955-962
Biology (General)
QH301-705.5
Arctic
Online Access:https://doi.org/10.1016/j.apjtb.2016.06.007
https://doaj.org/article/a1a4db013d864cf3b8250c84d04e2e8b
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Summary:Objective: To verify that Proliverenol has a potential ability in protecting cells from ethanol-induced hepatotoxicity. Methods: Activity of Proliverenol against ethanol-induced apoptosis was evaluated at mRNA and protein levels in HepG2 cell exposed to Proliverenol for 1 and 3 h. Results: Proliverenol conferred hepatoprotective activity through increasing cell survival up to 53%–69% via up-regulation of APEX1 DNA repair enzyme for 3.0–4.7 fold and down-regulating of nuclear factor-κB, tumor necrosis factorα and caspase-8 expression, allowing them to prevent 4.5–6.9 fold of alanine aminotransferase (ALT) leakage in HepG2 cells. Our finding revealed that Proliverenol repressed expression of ALT, which is significantly important as possible alternative mechanism for increased blood transaminase activities. In addition, the result also showed that caspase-8 pathway seemed to be involved in the molecular pathway rather than directly inducing mitochondrial damage. Conclusions: The data support our hypothesis that Proliverenol has a potential ability in protecting cells from ethanol-induced hepatotoxicity. We propose that Proliverenol provides hepatoprotective activity through up-regulating expression of APEX1 that repress DNA fragmentation, and down-regulating expression of nuclear factor-κB, tumor necrosis factorα and caspase-8, which therefore repress ALT leakage and its expression.

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