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Synergy of Phospholipid—Drug Formulations Significantly Deactivates Profibrogenic Human Hepatic Stellate Cells

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Institute of Pharmacy, Friedrich Schiller University Jena, Otto Schott Strasse 41, 07745 Jena, Germany
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Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(12), 676; https://doi.org/10.3390/pharmaceutics11120676
Received: 25 October 2019 / Revised: 6 December 2019 / Accepted: 9 December 2019 / Published: 12 December 2019
The pivotal role of hepatic stellate cells (HSCs) in orchestrating the bidirectional process of progression and regression of liver fibrosis makes them an ideal target for exploring new antifibrotic therapies. Essential phospholipids (EPLs), with their polyenylphosphatidylcholine (PPC) fraction, either alone or combined with other hepatoprotective substances such as silymarin, are recommended in hepatic impairment, but a scientific rationale for their use is still lacking. Herein, we compared the ability of EPLs to restore quiescent-like features in HSCs with that of dilinoleoylphosphatidylcholine (DLPC), PPC fraction’s main component. Specifically, we screened at the cellular level the antifibrotic effects of PPC formulations in the presence and absence of silymarin, by using LX-2 cells (pro-fibrogenic HSCs) and by assessing the main biochemical hallmarks of the activated and deactivated states of this cell line. We also proved the formulations’ direct effect on the motional order of cell membranes of adherent cells. LX-2 cells, examined for lipid droplets as a quiescence marker, showed that PPCs led to a more prominent deactivation than DLPC. This result was confirmed by a reduction of collagen and α-SMA expression, and by a profound alteration in the cell membrane fluidity. PPC–silymarin formulations deactivated HSCs with a significant synergistic effect. The remarkable bioactivity of PPCs in deactivating fibrogenic HSCs paves the way for the rational design of new therapeutics aimed at managing hepatic fibrosis. View Full-Text
Keywords: liver fibrosis; essential phospholipids; hepatic stellate cells; liposomes; silymarin; antifibrotic; reversion; quiescent; inactivation liver fibrosis; essential phospholipids; hepatic stellate cells; liposomes; silymarin; antifibrotic; reversion; quiescent; inactivation
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Valentino, G.; Zivko, C.; Weber, F.; Brülisauer, L.; Luciani, P. Synergy of Phospholipid—Drug Formulations Significantly Deactivates Profibrogenic Human Hepatic Stellate Cells. Pharmaceutics 2019, 11, 676.

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