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

Valentino, Gina; Zivko, Cristina; Weber, Florian; Brülisauer, Lorine; Luciani, Paola (2019). Synergy of Phospholipid—Drug Formulations Significantly Deactivates Profibrogenic Human Hepatic Stellate Cells. Pharmaceutics, 11(12) MDPI 10.3390/pharmaceutics11120676

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Valentino, Gina; Zivko, Cristina; Weber, Florian and Luciani, Paola

Subjects:

500 Science > 540 Chemistry
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health
600 Technology > 610 Medicine & health > 615 Pharmacology & therapeutics, prescription drugs

ISSN:

1999-4923

Publisher:

MDPI

Language:

English

Submitter:

Paola Luciani

Date Deposited:

15 Jan 2020 14:37

Last Modified:

30 Jun 2020 10:18

Publisher DOI:

10.3390/pharmaceutics11120676

PubMed ID:

31842373

Uncontrolled Keywords:

liver fibrosis; essential phospholipids; hepatic stellate cells; liposomes; silymarin; antifibrotic; reversion; quiescent; inactivation

BORIS DOI:

10.7892/boris.137020

URI:

https://boris.unibe.ch/id/eprint/137020

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