Biophysical methods: Complementary tools to study the influence of human steroid hormones on the liposome membrane properties.

Human steroid hormones are involved in many aspects of physiology and have long been known to exert rapid and delayed effects. They are lipophilic molecules which can be incorporated into the lipid membranes. Through non-covalent interactions they can alter the properties of the membrane, including fluidity, lipid raft formation and others. In this review, different biophysical techniques were described to study the interaction of human steroid hormones with biological and biomimetic membranes such as differential scanning calorimetry, electron paramagnetic resonance, fluorescence spectroscopy and Fourier transform infrared spectroscopy. The aim of this review is to overview the results of these complementary biophysical techniques summarizing the effects of these hormones on thermotropic and dynamic membrane properties. Meanwhile, the disorder induced by human steroid hormones is discussed in terms of hydrophobicity and chemical structure.

Interaction of triterpenoids with human serum albumin: A review.

Triterpenoids are a large group of natural and synthetic products. This review deals with the current state of knowledge on their interaction with serum albumin. The binding of drugs to albumin may control their distribution in tissues. In literature, different techniques were used to investigate the albumin-triterpenoid interaction and include fluorescence spectroscopy, Fourier transform infrared spectroscopy, circular dichroism, calorimetric techniques and molecular modeling. Changes in fluorescence intensity of albumin were observed upon triterpenoid-albumin complex formation. Thermodynamic analyses proved that hydrophobic interactions and hydrogen bonds were the mainly binding forces in triterpenoid-albumin systems. Molecular docking and site marker competitive experimental results revealed that triterpenoids bound to Sudlow's site I of albumin. Furthermore, Fourier transform infrared spectroscopy and circular dichroism spectra analysis indicated that the native conformation of the protein is affected upon binding to triterpenoids.

Interaction of glucocorticoids and progesterone derivatives with human serum albumin.

Glucocorticoids (GCs) and progesterone derivatives (PGDs) are steroid hormones with well-known biological activities. Their interaction with human serum albumin (HSA) may control their distribution. Their binding to albumin is poorly studied in literature. This paper deals with the interaction of a series of GCs (cortisol, cortisone, prednisolone, prednisone, 6-methylprednisolone and 9-fluorocortisol acetate) and PGDs (progesterone, hydroxylated PGDs, methylated PGDs and dydrogesterone) with HSA solution (pH 7.4) at molar ratios steroid to HSA varying from 0 to 10. Similar titrations were conducted using Trp aqueous solution. Fluorescence titration method and Fourier transform infrared spectroscopy (FTIR) are used. PGDs (except dydrogesterone), cortisone and 9-fluorocortisol acetate affected weakly the fluorescence of Trp in buffer solution while they decreased in a dose-dependent manner that of HSA. Their binding constants to HSA were then calculated. Moreover, displacement experiment was performed using bilirubin as a site marker. The binding constant of bilirubin to albumin was determined in the absence and presence of a steroid at a molar ratio steroid to HSA of 1. The results indicate that the steroids bind to HSA at site I in a pocket different from that of bilirubin. Furthermore, the peak positions of amide I and amide II bands of HSA were shifted in the presence of progesterone, dydrogesterone and GCs. Also a variation was observed in amide I region indicating the formation of hydrogen bonding between albumin and steroids.

Tetra- and Penta-Cyclic Triterpenes Interaction with Lipid Bilayer Membrane: A Structural Comparative Study.

The effect of tetracyclic (cortisol, prednisolone, and 9-fluorocortisol acetate) and pentacyclic (uvaol and erythrodiol) triterpenes (TTPs) on the fluidity of dipalmitoyl phosphatidyl choline (DPPC) liposome membrane was investigated by differential scanning calorimetry, Raman spectroscopy, and fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH). Liposomes were prepared in the absence and presence of TTPs at molar ratios DPPC:TTP 100:1, 100:2.5, and 100:10. All the studied TTPs abolished the pre-transition and modified the intensity of the Raman peak at 715 cm(-1) proving the interaction of TTP molecules with the choline head group of phospholipids. An increase in the Raman height intensity ratios of the peaks I 2935/2880, I 2844/2880, and I 1090/1130, giving information about the ratio disorder/order of the alkyl chains, and a decrease of the main transition temperature demonstrated the interaction of TTPs with the alkyl chains. The tetracyclic TTPs produced broadening of the phase transition profile. Besides, a scarcely splitting of the main transition peak was obtained with prednisolone and 9-fluorocortisol acetate. The results of fluorescence depolarization of DPH showed that the studied molecules fluidized the liposomal membrane at 25, 41, and 50 °C. Pentacyclic TTPs, being more hydrophobic than tetracyclic ones, demonstrated higher fluidizing effect than tetracyclic TTPs in the liquid crystalline phase suggesting a deeper incorporation in the lipid bilayer. The presence of a free polar head group at the ring D seems to control the TTP incorporation in the bilayer and consequently its effect on the membrane fluidity.

Effect of Progesterone, Its Hydroxylated and Methylated Derivatives, and Dydrogesterone on Lipid Bilayer Membranes.

The interaction of progesterone (PG), 17-hydroxyprogesterone (17-OHPG), 21-hydroxyprogesterone (21-OHPG), medroxyprogesterone (MP), medroxyprogesterone acetate (MPA), and dydrogesterone (DYG), with zwitterionic dipalmitoyl phosphatidylcholine (DPPC) multilamellar liposome, was investigated as a function of drug concentration using Fourier transform infrared spectroscopy and differential scanning calorimetry. The results reveal that progesterone and its derivatives changed the physical properties of the DPPC bilayers by decreasing the main phase-transition temperature (T m) and enthalpy (ΔH m), abolishing the pre-transition and disordering the membrane. From the thermodynamic parameters analysis, we concluded that PG, 21-OHPG, and MPA are localized inside the membrane. Whereas, the insertion of 17-OHPG in the lipid bilayers cannot be excluded in view of the significant decrease in the transition enthalpy at two molar ratios. MP and DYG are rather localized near the polar heads of phospholipids at the interface water-lipid bilayer. PG derivatives increase the membrane fluidity in the order: PG ≈ 21-OHPG ≈ MPA > 17-OHPG > MP ≈ DYG. The distinct effects produced by steroids are discussed in terms of hydrophobicity and chemical structure.