ABSTRACT
Silibinin, a natural plant flavonolignan is the main active constituent found in milk thistle (Silybum marianum). It is known to have hepatoprotective, anti-neoplastic effect, and suppresses lipid accumulation in adipocytes. Objective of this study was to investigate the effect of silibinin on adipogenic differentiation and thermogenic capacity of human adipose tissue derived mesenchymal stem cells. Silibinin (10 µM) treatment, either at the beginning or at the end of adipogenic differentiation, resulted in an increase of SIRT-1, PPARα, Pgc-1α, and UCPs gene expression. Moreover, silibinin administration resulted in a decrease of PPARγ, FABP4, FAS, and MEST/PEG1 gene expression during the differentiation, confirming that this compound is able to reduce fatty acid accumulation and adipocyte size. Our data showed that silibinin regulated adipocyte lipid metabolism, inducing thermogenesis and promoting a brown remodeling in adipocyte. Taken together, our findings suggest that silibinin increases UCPs expression by stimulation of SIRT1, PPARα, and Pgc-1α, improved metabolic parameters, decreased lipid mass leading to the formation of functional adipocytes.
ABSTRACT
Previous studies have clarified the molecular mechanism of photosensitization on red blood cell membranes induced by some drugs belonging to the class of nonsteroidal antiinflammatory drugs: ketoprofen, naproxen, and diflunisal. This process involves the participation of photodegradation products, free radicals, and reactive oxygen species. The aim of the present paper is to investigate the photohemolytic process using red blood cells of mammalian species, with different membrane phospholipid compositions. Human and bovine red blood cell membranes were selectively enriched with phosphatidylcholine and sphingomyelin. For this purpose, a new approach for phospholipid investigation was undertaken. Moreover, the phototoxic effect was tested with liposomes at different phospholipid compositions. A structure-function relationship between the erythrocyte membrane phospholipid composition and the photohemolytic process induced by the sensitizers can be proposed. Indeed, the different contents of the photoperoxidable double bond and the variable architecture of the membrane bilayer, due to the different phosphatidylcholine and sphingomyelin contents, strongly influence the resistance of the cell to an osmotic shock induced by photogenerated transient species or by the lytic activity of drug photoproducts. The higher content of sphingomyelin, its asymmetric disposition at the outer surface of membrane bilayers, the high level of saturated acyl fatty chains, and the presence of photoperoxidable trans double bonds in the hydrophilic region greatly decrease the fluidity of bilayers and enhance the resistance of the membrane to phototoxic damage. On the other hand, an increase in the content of phosphatidylcholine, which is rich in species with unsaturated acyl fatty chains, decreases the membrane resistance, because these latter can be easily oxidized by drug-photogenerated reactive oxygen species.
