Bile Salt Molecules Research Articles

Modification of coconut residue fiber and its bile salt adsorption mechanism: Action mode of insoluble dietary fibers probed by microrheology

The effect of dietary fiber on lowering blood cholesterol level depends on its ability to separate bile salt (BS) and prevent its recycling. The effects of composition and microstructure of coconut residue fiber (CRF) by modifying on BS retention and adsorption process were studied, and the adsorption mechanism of BS by insoluble dietary fiber (IDF) was investigated. We proved for the first time that adding 0.38 wt% of chitosan to assist in CRF self-assembly could improve effectively IDF's ability to retain multiple BS molecules. The adsorption of CRF to BS was a combination of two modes: rapid adsorption at the initial stage and slow adsorption after the initial stage. The fast adsorption mode plays a dominant role during the early stage of adsorption and is correlated with the viscosity and soluble diary fiber (SDF) content in dietary fiber (DF). In contrast, the slow adsorption mode occurs during the whole adsorption process while plays a dominant role during the middle and late adsorption stages. This mode is also correlated with the non-covalent transient network formed by DF in the system. The formation of a non-covalent transient network is a dynamic process in which the formation and collapse of the system occurs alternately; and this formation relies on the content of free H-bonds in IDF. This study can be helpful for the understanding of the BS-adsorption mechanism of ordinary diary fiber.

Tuning lipid structure by bile salts: Hexosomes for topical administration of catechin

The delivery of bio-active molecules through the skin is challenging given the complex structure of its outer layer, the stratum corneum. Here we explore the possibility to encapsulate natural compounds into nanocarriers containing permeation enhancers that can affect the fluidity of the stratum corneum lipids. This approach is expected to facilitate dermal or transdermal release. For this purpose, the application of bile salts, which are natural surfactants involved in vivo in lipid digestion, was exploited.Bile salts were added to lipid liquid crystalline nanoparticles (NPs) made of monoolein for antioxidant topical delivery. Monoolein self-assembly behaviour in water was affected by the presence of bile salts molecules, giving a transition from a bicontinuous cubic to unilamellar vesicles dispersion. By adding oleic acid (OA), the change of curvature in the system led to a reverse hexagonal phase. The morphology, structure and size of the nanocarriers was investigated before the nanoparticles were loaded with catechin, a natural antioxidant occurring in plants and food. The encapsulation did not affect significantly the formulation phase behaviour. The formulation loaded with bile salts and catechin was thereafter tested in vitro on the skin from new-born pig. The results for two different lipid formulations without bile salts were compared under the same experimental conditions and with the same antioxidant. The formulation with bile salts showed the best performance, allowing a superior permeation of catechin in the different skin layers in comparison with formulations without bile salt.

Simple Analysis of Primary and Secondary Bile Salt Hydrolysis in Mouse and Human Gut Microbiome Samples by Using Fluorogenic Substrates

Animals produce bile to act as an antibacterial agent and to maximize the absorption of lipophilic nutrients in the gut. The physical properties of bile are largely dictated by amphipathic bile salt molecules, which also participate in signaling pathways by modulating physiological processes upon binding host receptors. Upon excretion of bile salts from the gall bladder into the intestine, the gut microbiota can create metabolites with modified signaling capabilities. The category and magnitude of bile salt metabolism can have positive or negative effects on the host. A key modification is bile salt hydrolysis, which is a prerequisite for all additional microbial transformations. We have synthesized five different fluorogenic bile salts for simple and continuous reporting of hydrolysis in both murine and human fecal samples. Our data demonstrate that most gut microbiomes have the highest capacity for hydrolysis of host-produced primary bile salts, but some microbially modified secondary bile salts also display significant turnover.

Bile Salts: Natural Surfactants and Precursors of a Broad Family of Complex Amphiphiles.

Bile salts (BSs) are naturally occurring rigid surfactants with a steroidal skeleton and specific self-assembly and interface behaviors. Using bile salts as precursors, derivatives can be synthesized to obtain molecules with specific functionalities and amphiphilic structure. Modifications on single molecules are normally performed by substituting the least-hindered hydroxyl group on carbon C-3 of the steroidal A ring or at the end of the lateral chain. This leads to monosteroidal rigid building blocks that are often able to self-organize into 1D structures such as tubules, twisted ribbons, and fibrils with helical supramolecular packing. Tubular aggregates are of particular interest, and they are characterized by cross-section inner diameters spanning a wide range of values (3-500 nm). They can form through appealing pH- or temperature-responsive aggregation and in mixtures of bile salt derivatives to provide mixed tubules with tunable charge and size. Other derivatives can be prepared by covalently linking two or more bile salt molecules to provide complex systems such as oligomers, dendrimers, and polymeric materials. The unconventional amphiphilic molecular structure imparts specific features to BSs and derivatives that can be exploited in the formulation of capsules, drug carriers, dispersants, and templates for the synthesis of nanomaterials.

Calcium Alters the Interfacial Organization of Hydrolyzed Lipids during Intestinal Digestion.

Calcium plays an important dual role in lipid digestion: promoting removal of long-chain fatty acids from the oil-water interface by forming insoluble calcium soaps while also limiting their bioaccessibility. This becomes more significant in food containing high calcium concentration, such as dairy products. Nevertheless, scarce attention has been paid to the effect of calcium on the interfacial properties during lipid digestion, despite this being largely an interfacial reaction. This study focused on the dynamics of the formation of calcium soaps at the oil-water interface during lipolysis by pancreatic lipase in the absence and presence of the two primary human bile salts (sodium glycocholate or sodium glycochenodeoxycholate). The competitive adsorption of lipase, bile salts, and lipolysis products, as well as the formation of calcium soaps in the presence of increasing concentrations of calcium were mainly characterized by recording the interfacial tension and dilatational modulus in situ. In the absence of bile salts, calcium complexes with fatty acids at the oil-water interface forming a relatively strong viscoelastic network of calcium soaps over time. The dilatational modulus of the calcium soap network is directly related to the interfacial concentration of lipolysis products and the calcium bulk concentration. Calcium soaps are also visualized forming a continuous rough layer on the surface of oil droplets immersed in simulated intestinal aqueous phase. Despite bile salts having different surface activity, they play a similar role on the interfacial competition with lipase and lipolysis products although altering their kinetics. The presence of bile salts disrupts the network of calcium soaps, as suggested by the decrease in the dilatational modulus and the formation of calcium soap islands on the surface of the oil droplets. The accelerant effect of calcium on lipolysis is probably because of fatty acid complexation and subsequent removal from the interface rather than reduced electrostatic repulsion between lipase and bile salt molecules and promoted lipase adsorption. The work shown here has implications for the delivery of oil-soluble bioactives in the presence of calcium.

Influence of bile salt on vitamin E derived vesicles involving a surface active ionic liquid and conventional cationic micelle

This study has been actually performed with the aim to develop vitamin E derived vesicles individually from a surface active ionic liquid (1-Hexadecyl-3-Methylimidazolium chloride ([C16mim]Cl)) and a common cationic amphiphile (benzyldimethylhexadecylammonium chloride (BHDC)) and also to investigate their consequent breakdown in presence of bile salt molecule. From this study, it is revealed that the rotational motion of coumarin 153 (C153) molecule is hindered as the vitamin E content is increased in the individual micellar solution of [C16mim]Cl and BHDC. The extent of enhancement in rotational relaxation time is more pronounced in case of [C16mim]Cl-vitamin E solutions than in the BHDC-vitamin E vesicular aggregates which confirms the greater rigidity of the former vesicular system than the later one. Moreover, the effect of bile salt in the vitamin E forming vesicular assemblies have also been unravelled. It is found that the large area occupancy by the steroidal backbone of the bile salt plays a crucial role towards the enlargement of the average surfactant head group area. This results in disintegration of the vesicles composed of vitamin E and consequently, vesicles are transformed into mixed micellar aggregates. From the anisotropy measurement it is found that the rotational motion of C153 is more hindered in the [C16mim]Cl/BHDC-NaCh mixed micelles compared to that inside the individual vesicles. The fluorescence correlation spectroscopic (FCS) study also confirms that the mixed micelles have a more compact structure than that of the [C16mim]Cl-vitamin E and BHDC-vitamin E vesicles. Altogether, the micelle to vesicle transition involving any vitamin and their disruption by bile salt would be an interesting investigation both from the view point of basic colloidal chemistry and towards the generation of new drug delivery vehicle due to their unique microenvironment. Therefore, in future, these systems can be utilised as vehicle for the transport and as well as delivery of drugs and as probable reactor in nanomaterial synthesis.

Study on Micelle Formation of Bile Salt Using Nuclear Magnetic Resonance Spectroscopy.

1H-nuclear magnetic resonance (1H-NMR) measurements can identify the specific protons that contribute to interactions between molecules. Using this technique, micelles formed by four bile salts: sodium taurocholate (NaTC), taurodeoxycholate (NaTDC), taurochenodeoxycholate (NaTCDC), and tauroursodeoxycholate (NaTUDC) were measured and compared in viewpoint of molecular interactions. Rotating-frame nuclear Overhauser effect and exchange spectroscopy (ROESY) analysis of the four bile salts showed differences with respect to the type of micelle formation. For all four bile salts, the key protons contributing to hydrophobic interactions were found to be the methyl protons at positions 18 and 19. The cross-peak patterns for the four bile salt species indicated pairs of characteristic proton depending on a bile salt species. The spin-lattice relaxation time (T1) of the alkyl side-chain in NaTC was relatively long compared to that of the three other bile salts, even when the concentration was higher than the critical micelle concentration (cmc). This unique behavior indicates that the hydrophilic region of NaTC molecules is flexible within their micelles. Moreover, T1 values for the typically hydrophobic methyl protons at sites C18 and C19 of NaTC were almost constant above the cmc. These results may suggest that NaTC micelles remain as small primary structures in solution unlike the three other bile salt molecules investigated in the study.

Self-assembly of micelles in organic solutions of lecithin and bile salt: Mesoscale computer simulation

We propose a coarse-grained model for studying the effects of adding bile salt to lecithin organosols by means of computer simulation. This model allows us to reveal the mechanisms of experimentally observed increasing of viscosity upon increasing the bile salt concentration. We show that increasing the bile salt to lecithin molar ratio induces the growth of elongated micelles of ellipsoidal and cylindrical shape due to incorporation of disklike bile salt molecules. These wormlike micelles can entangle into transient network displaying perceptible viscoelastic properties.

Interaction of Bile Salts with β-Cyclodextrins Reveals Nonclassical Hydrophobic Effect and Enthalpy-Entropy Compensation.

Herein, we present an endeavor toward exploring the lacuna underlying the host:guest chemistry of inclusion complex formation between bile salt(s) and β-cyclodextrin(s) (βCDs). An extensive thermodynamic investigation based on isothermal titration calorimetry (ITC) demonstrates a dominant contribution from exothermic enthalpy change (ΔH < 0) accompanying the phenomenon of inclusion complex formation, along with a relatively smaller contribution to total free energy change from the entropic component. However, the negative heat capacity change (ΔCp < 0) displays the hallmark for a pivotal role of hydrophobic effect underlying the interaction. Contrary to the classical hydrophobic effect, such apparently paradoxical thermodynamic signature has been adequately described under the notion of "nonclassical hydrophobic effect". On the basis of our results, the displacement of disordered water from hydrophobic binding sites has been argued to mark the enthalpic signature and the key role of such interaction forces is further corroborated from enthalpy-entropy compensation behavior showing indication for almost complete compensation. To this end, we have quantified the interaction of two bile salt molecules (namely, sodium deoxycholate and sodium glycocholate) with a series of varying chemical substituents on the host counterpart, namely, βCD, (2-hydroxypropyl)-βCD, and methyl βCD.

Dispersion and Individualization of SWNT in Surfactant-Free Suspensions and Composites of Hydrosoluble Polymers

We propose a simple and original way to prepare surfactant-free SWNT/hydrosoluble polymer composites with high concentrations of individual SWNT. We first disperse single-walled carbon nanotubes (SWNT) in aqueous suspensions using bile salts (BS), and we mix them with a solution of hydrosoluble polymer, poly(vinylpyrrolidone) (PVP) or poly(vinyl alcohol) (PVA). We measure the yield using visible–NIR absorption spectroscopy, and we probe both the chemical environment of the nanotubes and the effectiveness of individualization from coupled Raman/photoluminescence studies. We evidence a direct exchange of BS molecules and PVA chains at the surface of SWNT. By contrast, no direct exchange is observed with PVP. On the other hand, we show that a simple dialysis process leads to the preparation of aqueous suspensions of SWNT covered by PVP or PVA with high yields and an effective individualization of the nanotubes.

Thermodynamic Study of Bile Salts Micellization

The aggregation process of sodium cholate, NaC, sodium deoxycholate, NaDC, sodium glycocholate, NaG, sodium glycodeoxycholate, NaDG, sodium taurocholate, NaT, and sodium taurodeoxycholate, NaDT in aqueous solution has been investigated at several temperatures, in the absence and in the presence of NaCl 0.15 mol kg–1. Results show that both a decrease in the number of ring hydroxyls and an increase in the length of the side chain favor micellization, in the absence as well as in the presence of salt. These observations can be explained by considering that the hydrophobic effect is the driving force for the self-association process. This is in agreement with the ΔmicCp° values, which point out that the micellization process leads to a diminution of the hydrophobic surface of the bile salt molecules exposed to water. The presence of NaCl 0.15 mol kg–1 in the aqueous phase favors micellization by decreasing the CMC due to a diminution in the electrostatic repulsions within the micelles. However the presence o...

Formation and dynamics of "waterproof" photoluminescent complexes of rare earth ions in crowded environment.

Understanding behavior of rare-earth ions (REI) in crowded environments is crucial for several nano- and bio-technological applications. Evolution of REI photoluminescence (PL) in small compartments inside a silica hydrogel, mimic to a soft matter bio-environment, has been studied and explained within a solvation model. The model uncovered the origin of high PL efficiency to be the formation of REI complexes, surrounded by bile salt (DOC) molecules. Comparative study of these REI-DOC complexes in bulk water solution and those enclosed inside the hydrogel revealed a strong correlation between an up to 5×-longer lifetime of REIs and appearance of the DOC ordered phase, further confirmed by dynamics of REI solvation shells, REI diffusion experiments and morphological characterization of microstructure of the hydrogel.

Study on interaction of bile salts with curcumin and curcumin embedded in dipalmitoyl-sn-glycero-3-phosphocholine liposome

Curcumin, often used as a food spice, is a natural polyphenol that has various medicinal benefits such as anti-cancer, anti-amyloid, anti-oxidant, and anti-inflammatory properties, among others. The interaction between bile salts having physiological significance and curcumin suggests the aggregation of bile salts dramatically alters the absorption and fluorescence parameters of curcumin. The fluorescence emission maximum as well as the intensity can easily detect critical micellar concentration of sodium cholate and sodium deoxycholate respectively to be 16 and 6mM at room temperature. The mechanism of interaction of curcumin with bile salts has been presented at low, intermediate and high bile salt concentrations and depends on temperature. In the presence of bile salts the DPPH scavenging activity was preserved, though less than in the presence of curcumin alone. The effect of submicellar concentration, 5–50μM, of bile salt with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes in solid gel and liquid crystalline phases has been investigated using curcumin as an embedded probe in the membrane. The curcumin based fluorescence probing method indicates even at very low concentration, ∼5μM, incorporation of monomeric bile salt molecules disorders the membrane properties. Expulsion of curcumin from the membrane in the presence of bile salt is ruled out, suggesting wetting of membrane. Alteration of membrane fluidity by bile salts is found to have an opposing effect in the liquid crystalline phase compared to in the solid gel phase, and is sensitive to the nature of bile salt. The permeability in the liquid crystalline phase decreases in the presence of bile salt. The phase transition temperature of the membrane is influenced by bile salt.

Mixed Micellization and Mixed Monolayer Formation of Sodium Cholate and Sodium Deoxycholate in Presence of Hydrophobic Salts Under Physiological Conditions

AbstractMixed micellization and mixed monolayer formation of two bile salts namely sodium cholate (NaC) and sodium deoxycholate (NaDC), in the presence of sodium chloride (NaCl) and three hydrophobic salts including sodium acetate (NaAc), sodium butanoate (NaBu) and sodium hexanoate (NaHx) in 10 mM phosphate buffer (pH 6.5) at 37 °C were investigated by means of surface tension measurements. The experimental results were utilized to evaluate various parameters like critical micellar concentration (CMC), micellar and monolayer interaction parameter (β and βσ), micellar and monolayer mole fractions (X and Z), activity coefficients of two bile salts in mixed micelles and monolayer (f and f(σ)), surface excess (Γmax) and minimum surface area per molecule of bile salt (Amin). Mixed micelles and mixed monolayer were found to show slight non‐ideality and both these phenomena have been found to be affected differently in the presence of various additive salts with NaHx showing larger effects. Higher efficiency of NaHx in affecting both phenomena has been attributed to its appreciable hydrophobicity and surface activity, thus showing stronger interactions with bile salt molecules.

Reduced Graphene Oxide Nanosheets Functionalized with Bile Salts as Support for Electrochemical Catalysts

Graphene nanosheets functionalized with bile salts (G-bile salts) are obtained through chemical reduction of exfoliated graphite oxide in the presence of deoxycholic acid sodium salt, taurodeoxycholic acid sodium salt, or cholic acid sodium salt. Due to the “facial amphiphilic” structure of bile salt molecules, the G-bile salt composites exhibit excellent dispersibility in water. In addition, G-bile salts decorated with palladium (Pd) nanoparticles (Pd-G-bile salts) are prepared via a facile co-reduction process. The use of the Pd-G-bile salt composites as electrochemical catalysts for formic acid oxidation reaction is demonstrated. Better utilization has been achieved for Pd catalysts dispersed on G-bile salts than those prepared without bile salts.

Multiple prototropism of fisetin in sodium cholate and related bile salt media

Fisetin, a bioflavonoid, has important biological relevance. It exhibits intramolecular excited state proton transfer (ESIPT), analogous to the structurally similar flavonoids. The presence of multiple prototropic forms of fisetin was observed at various concentrations of different bile salt molecules. The presence of ground state fisetin anion (FA)(GS) (λ(ex) 418 nm; λ(em) 490 nm) in alcohols and bile salt micellar media is a novel observation. The interaction of fisetin with sodium cholate (NaC) and some other bile salts has been studied in detail, using the intrinsic fluorescence of different prototropic forms of fisetin: neutral form (FN, λ(ex) 369 nm, λ(em) ~ 400 nm), ground state anion form ((FA)(GS), λ(ex) 418 nm, λ(em) 490 nm) and phototautomer (FT, λ(ex) 369 nm, λ(em) 540 nm). The hypsochromic shift of (FA*)(ES) emission and bathochromic shift of FT emission with increasing bile salt concentration suggests the progressive reduction of polarity of the bile salt media, which could be resulting from the neutralization of bile salt molecules as their concentration increases.

Bile salt structural effect on the thermodynamic properties of a catanionic mixed adsorbed monolayer

The interfacial effects of two bile salts (sodium deoxycholate (NaDC) and sodium dehydrocholate (NaDHC)) in a catanionic mixed adsorbed monolayer have been investigated at 25 °C. The surfactant interfacial composition, the interfacial orientation of the molecules and the energy changes are analysed to show a thermodynamic evidence of the hydrophobic BSs effect during its intercalation into interfacial adsorbed didodecyldimethyl ammonium bromide (DDAB) molecules. Both mixed systems (NaDC–DDAB and NaDHC–DDAB) have analogous adsorption efficiencies, which are similar from a pure DDAB monolayer and superior to that obtained for both bile salts molecules. Nevertheless, their adsorption effectiveness is different: NaDC causes an increment of Γ while NaDHC produces the opposite effect. The adsorption efficiency in surface tension reduction is due to the existence of interfacial synergistic interactions (confirmed by the analysis of β γ and ΔG ad 0 values). Maximum synergistic interaction is seen for α BSs = 0.4. The hydrophobic steroid backbone of NaDHC molecule presents a deep interfacial penetration than NaDC. This fact causes a great disturbance of DDAB hydrocarbon tails and conduces to a large separation of molecules (high A m values) which explains the reduction of adsorption effectiveness (low Γ m values).

Tween 80−Sodium Deoxycholate Mixed Micelles: Structural Characterization and Application in Doxorubicin Delivery

The objective of the present investigation is to develop and characterize anionic mixed micelles of two biocompatible surfactants, Tween 80 (T-80) and sodium deoxycholate (NaDC), and evaluate their potential in the delivery of doxorubicin hydrochloride (DOX), a cationic anticancer drug. The mixed micelles were characterized for their microstructure, intermicellar interactions, and doxorubicin binding ability by dynamic light scattering, small angle neutron scattering (SANS), viscosity, and optical absorption measurements. Salt-induced growth of the mixed micelles at different compositions suggests that both electrostatic interaction of the anionic bile salts and steric repulsion of the ethylene oxide groups in nonionic components are affected by the presence of electrolytes. Addition of bile salt molecules to T-80 micelles suppresses the salt-induced growth of nonionic T-80 micelles. SANS studies indicate that bile salt micelles are prolate ellipsoidal in shape, and the addition of T-80 transforms them toward a spherical shape. The anionic bile salt can successfully bind to the cationic drug doxorubicin. The in vitro cytotoxicity studies in various cancer cell lines revealed that DOX-loaded micelles have greater in vitro anticancer activity as compared to DOX solution, indicating their potential in pharmaceutical applications.

1-Naphthol as a Sensitive Fluorescent Molecular Probe for Monitoring the Interaction of Submicellar Concentration of Bile Salt with a Bilayer Membrane of DPPC, a Lung Surfactant

In this study, 1-naphthol has been used as a sensitive ESPT fluorescent molecular probe to investigate the interaction of submicellar concentrations of two physiologically important bile salts, sodium deoxycholate and sodium cholate, with dipalmitoylphosphatidylcholine small unilamellar vesicles in solid gel and liquid crystalline phases. Steady-state and time-resolved fluorescence of the two excited state prototropic forms of 1-naphthol indicate that the incorporation of monomeric bile salt molecules in the lipid bilayer membrane induces appreciable wetting of the bilayer up to the hydrocarbon core region, even at very low (≤1 mM) concentrations of the bile salts.

Site‐Specific Investigation of the Steady‐State Kinetics and Dynamics of the Multistep Binding of Bile Acid Molecules to a Lipid Carrier Protein

The investigation of multi-site ligand-protein binding and multi-step mechanisms is highly demanding. In this work, advanced NMR methodologies such as 2D (1)H-(15)N line-shape analysis, which allows a reliable investigation of ligand binding occurring on micro- to millisecond timescales, have been extended to model a two-step binding mechanism. The molecular recognition and complex uptake mechanism of two bile salt molecules by lipid carriers is an interesting example that shows that protein dynamics has the potential to modulate the macromolecule-ligand encounter. Kinetic analysis supports a conformational selection model as the initial recognition process in which the dynamics observed in the apo form is essential for ligand uptake, leading to conformations with improved access to the binding cavity. Subsequent multi-step events could be modelled, for several residues, with a two-step binding mechanism. The protein in the ligand-bound state still exhibits a conformational rearrangement that occurs on a very slow timescale, as observed for other proteins of the family. A global mechanism suggesting how bile acids access the macromolecular cavity is thus proposed.