Molecular Mechanisms Underlying Hepatoprotective Activity of Lutein in the Context of Intestinal Failure-Associated Liver Disease.

Intestinal failure-associated liver disease (IFALD) is a spectrum of liver diseases occurring in patients not exposed to liver-damaging factors other than those linked to intestinal dysfunction. The pathogenesis of this disease is multifactorial. It is estimated that up to 90% of people taking long-term parenteral nutrition may develop IFALD, with particular risk for premature neonates and infants due to their immature antioxidant protection and bile acid metabolism. The lack of effective prevention and treatment methods for IFALD encourages scientists to search for new therapeutic solutions. The use of lutein as a substance with antioxidant and anti-inflammatory effects seems to be of great potential in such indication, especially since patients on parenteral nutrition are at risk of deficits in various plant-based nutrients, including lutein. In this review, we explain the pathogenesis of IFALD and summarize knowledge of the hepatoprotective properties of lutein, underscoring its potential as a treatment option. The hepatoprotective effects of lutein and their proposed mechanisms of action are supported by studies on cells and animals exposed to various liver-damaging factors, such as lipopolysaccharide, high-fat diet, alcohol, and more. Finally, we provide perspectives on the future application of lutein in therapy.

Natural bioactive compounds-The promising candidates for the treatment of intestinal failure-associated liver disease.

Parenteral nutrition (PN) is a life-saving procedure conducted to maintain a proper nutritional state in patients with severe intestinal failure who cannot be fed orally. A serious complication of PN therapy is liver failure, known as intestinal failure-associated liver disease (IFALD). The pathogenesis of IFALD is multifactorial and includes inhibition of the farnesoid X receptor (FXR) by PN components, bacteria translocation from impaired intestines, and intravenous line-associated bloodstream infection. Currently, the most frequently researched therapeutic option for IFALD is using lipid emulsions based on soy or fish oil and, therefore, free from phytosterols known as FXR antagonists. Nevertheless, the potential side effects of the lack of soybean oil delivery seem to outweigh the benefits, especially in the pediatric population. PN admixture provides all the necessary nutrients; however, it is deprived of exogenous natural bioactive compounds (NBCs) of plant origin, such as polyphenols, characterized by health-promoting properties. Among them, many substances have already been known to demonstrate the hepatoprotective effect in various liver diseases. Therefore, searching for new therapeutic options for IFALD among NBCs seems reasonable and potentially successful. This review summarizes the recent research on polyphenols and their use in treating various liver diseases, especially metabolic dysfunction-associated steatotic liver diseases (MASLD). Furthermore, based on scientific reports, we have described the molecular mechanism of action of selected NBCs that exert hepatoprotective properties. We also summarized the current knowledge on IFALD pathogenesis, described therapeutic options undergoing clinical trials, and presented the future perspective of the potential use of NBCs in PN therapy.

The Development of Magnolol-Loaded Intravenous Emulsion with Low Hepatotoxic Potential.

Intestinal failure-associated liver disease (IFALD) is a severe liver injury occurring due to factors related to intestinal failure and parenteral nutrition administration. Different approaches are studied to reduce the risk or ameliorate the course of IFALD, including providing omega-3 fatty acids instead of soybean oil-based lipid emulsion or administering active compounds that exert a hepatoprotective effect. This study aimed to develop, optimize, and characterize magnolol-loaded intravenous lipid emulsion for parenteral nutrition. The preformulation studies allowed for chosen oils mixture of the highest capacity of magnolol solubilization. Then, magnolol-loaded SMOFlipid was developed using the passive incorporation method. The Box-Behnken design and response surface methodology were used to optimize the entrapment efficiency. The optimal formulation was subjected to short-term stress tests, and its effect on normal human liver cells and erythrocytes was determined using the MTT and hemolysis tests, respectively. The optimized magnolol-loaded SMOFlipid was characterized by the mean droplet diameter of 327.6 ± 2.9 nm with a polydispersity index of 0.12 ± 0.02 and zeta potential of -32.8 ± 1.2 mV. The entrapment efficiency of magnolol was above 98%, and pH and osmolality were sufficient for intravenous administration. The magnolol-loaded SMOFlipid samples showed a significantly lower toxic effect than bare SMOFlipid in the same concentration on THLE-2 cells, and revealed an acceptable hemolytic effect of 8.3%. The developed formulation was characterized by satisfactory stability. The in vitro studies showed the reduced cytotoxic effect of MAG-SMOF applied in high concentrations compared to bare SMOFlipid and the non-hemolytic effect on human blood cells. The magnolol-loaded SMOFlipid is promising for further development of hepatoprotective lipid emulsion for parenteral nutrition.

Etoricoxib-Cannabidiol Combo: Potential Role in Glioblastoma Treatment and Development of PLGA-Based Nanoparticles.

BACKGROUND: Glioblastoma (GBM) is the most frequently occurring primary malignant central nervous system tumor, with a poor prognosis and median survival below two years. Administration of a combination of non-steroidal anti-inflammatory drugs and natural compounds that exhibit a curative or prophylactic effect in cancer is a new approach to GBM treatment. This study aimed to investigate the synergistic antitumor activity of etoricoxib (ETO) and cannabidiol (CBD) in a GBM cell line model, and to develop poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) for these two substances. METHODS: The activity of ETO+CBD was determined using the MTT test, cell-cycle distribution assay, and apoptosis analysis using two GBM cell lines, namely, T98G and U-138 MG. The PLGA-based NPs were developed using the emulsification and solvent evaporation method. Their physicochemical properties, such as shape, size, entrapment efficiency (EE%), in vitro drug release, and quality attributes, were determined using scanning electron microscopy, diffraction light scattering, high-performance liquid chromatography, infrared spectroscopy, and differential scanning calorimetry. RESULTS: The combination of ETO and CBD reduced the viability of cells in a dose-dependent manner and induced apoptosis in both tested GBM cell lines. The developed method allowed for the preparation of ETO+CBD-NPs with a spherical shape, mean particle size (MPS) below 400 nm, zeta potential (ZP) values from -11 to -17.4 mV, polydispersity index (PDI) values in the range from 0.029 to 0.256, and sufficient EE% of both drugs (78.43% for CBD, 10.94% for ETO). CONCLUSIONS: The combination of ETO and CBD is a promising adjuvant therapeutic in the treatment of GBM, and the prepared ETO+CBD-NPs exhibit a high potential for further pharmaceutical formulation development.