Trombinol, a bioactive fraction of Psidium guajava, stimulates thrombopoietin expression in HepG2 cells

Objective To study the regulation of trombinol on thrombopoietin, an essential regulator of thrombocyte production. Methods Effect of trombinol on thrombopoietin regulation was evaluated at the mRNA and protein levels in human hepatoma HepG2 cells. The mRNA expressions were revealed by PCR and real-time PCR, while the protein expressions were analyzed using western blotting and human ELISA kit. Statistical differences between the test were determined by student's t-test with P < 0.05 was considered statistically significant. Results Trombinol significantly increased the expression of thrombopoietin at the level of mRNA and protein secretion in HepG2 cell lines. Trombinol with the concentration of 15 μg/mL, positively induces 2.5-fold of thrombopoietin expression. Up-regulation of GABP, a transcription factor of thrombopoietin, is suggested to be involved in cellular regulatory mechanisms of trombinol. Here, our result shows convincing evidence that trombinol affects the thrombopoietin productions in vitro. This molecular explanation of thrombopoietin's stimulating function is in line with the traditional use of Psidium guajava for treatment of diseases involving thrombocytopenia. Conclusions Thrombopoietin stimulating function of trombinol could be potentially considered as one of alternative treatment for thrombocytopenia-related cases, including post chemotherapy shock, dengue fever and liver failure.

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 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.