Comparison of solubilization capacity of resveratrol in sodium 3α, 12α -dihydroxy-7-oxo-5 ß-cholanoate and sodium dodecyl sulfate.

In this study we investigated resveratrol (trans-3,5,4'-trihydroxystilbene) solubilization with sodium 3α,12 α-dihydroxy-7-oxo-5 ß-cholanoate (S7-OD) and sodium dodecyl sulfate (SDS). The investigation was aimed at determining whether large spherical micelles (SDS) or small longitudinal micelles (S7-OD) are more convenient for incorporation of resveratrol. Also, we studied resveratrol behavior in mixed micelles with mentioned surfactants using spectroflourimetric method as well as the effects of sodium chloride and urea on resveratrol solubilization capacity in the applied surfactants. Resveratrol solubilization curve was different in the investigated surfactants. Resveratrol solubilization curve for sodium 3α,12 α-dihydroxy-7-oxo-5 ß-cholanoate at concentration 0.9 CMC reached saturation level of 60% dissolved resveratrol. The curve for sodium dodecyl sulfate was linear within the whole range of the investigated concentration; resveratrol solubilization rate reached 13% at 2 CMC. In S7-OD, NaCl increased capacity of resveratrol solubilization up to 1.4 CMC surfactant concentration, whilst maximum level of dissolved resveratrol (90%) was observed at 0.9 CMC. In SDS, NaCl decreased resveratrol solubilization capacity. Urea reduced resveratrol solubilization rate in sodium 3α ,12 α-dihydroxy-7-oxo-5 ß-cholanoate, whereas it had inverse effect in sodium dodecyl sulfate. The obtained results strongly suggest that structure, that is, shape, of the surfactant micelles significantly affects their capacity of resveratrol solubilization. Also, presence of NaCl and urea influences solubilization capacities of investigated surfactants.

Effect of potassium channel opener pinacidil on the contractions elicited electrically or by noradrenaline in the human radial artery.

In order to discover an agent that can prevent spasm of the human radial artery, the aim of our study was to evaluate the effect of the K(+) channel opener, pinacidil, on contractions in the radial artery. Contractions of the radial artery were evoked by exogenously applied noradrenaline or by electrical field stimulation (EFS, 20Hz, neurogenic). Pinacidil induced concentration-dependent inhibition of both EFS- and noradrenaline-evoked contractions of the radial artery. Glibenclamide, a selective blocker of ATP-sensitive K(+) channels (Kir6.x containing subunit) antagonized in the same manner the pinacidil-induced inhibition of neurogenic contractions and contractions evoked by exogenous noradrenaline. The inhibition of pinacidil relaxation by tetraethylammonium (TEA), a blocker of Ca-sensitive K(+) (K(Ca)) channels, was more pronounced in EFS-contracted preparations. A blocker of voltage-sensitive K(+) (K(V)) channels, 4-aminopyridine (4-AP), inhibited pinacidil relaxation only in EFS-contracted preparations. In order to test the presence of different K(+) channels, immunohistochemistry of K(+) channels expression in the radial artery was performed. The vascular wall of the human radial artery showed variable positivity with the following applied antibodies: Kv1.2, Kv1.3, Kir6.1, and K(Ca)1.1. The antibodies against Kv1.6, Kv2.1, and Kir6.2 channel subunits were completely negative. These results suggest that the inhibitory effect of pinacidil on contractions of the human radial artery might be postsynaptic and associated with opening of smooth muscle Kir6.1-containing K(ATP) channels. TEA- and 4-AP-sensitive K(+) channels may also contribute to pinacidil effect in the human radial artery.

Isoflavone composition, total polyphenolic content, and antioxidant activity in soybeans of different origin.

Twenty soybean cultivars, originating from the United States, Russia, Serbia, and China, were analyzed for their isoflavone composition, total polyphenolic content, and antioxidant activity. Isoflavones were extracted by aqueous methanol (80%) and analyzed by high-performance liquid chromatography/diode array detection. Precision and linearity of the applied method were within the standard limits of validation. The highest and the lowest total isoflavone contents were 4.59 and 1.45 mg/g of dried soybean weight, respectively. A significant difference (P < .05) was found in isoflavone concentration among the different cultivars, but it was observed that origin is not a significant factor that could influence isoflavone content in soybeans. Total polyphenolic content varied between 2.13 and 3.45 mg of gallic acid equivalents/g of dried soybean weight. The free radical scavenging activity of soybean extracts assayed by 2,2-diphenyl-1-picrylhydrazyl in terms of 50% inhibitory concentration (IC(50)) ranged from 1.40 to 3.35 mg/mL. Negative correlation between total polyphenolic content and IC(50) was observed, but there was no correlation between total isoflavone content and IC(50). On the basis of this study, soybean cultivars with larger potency for biological activity could be recognized.

Determination of trans- and cis-resveratrol in Serbian commercial wines.

Resveratrol (trans-3,5,4'-trihydroxystilbene) is a phytoalexin produced by grapevines in response to fungal infection, particularly to Botrytis cinerea. It has been shown that it possess various biological effects such as prevention of cardiovascular diseases and anti-inflammatory and anticancerogenic properties. Red wines are a primary source of resveratrol. Although a number of investigations have focused on the determination of resveratrol in wines of different countries, there is no similar study about the wines produced in Serbia. As authors are aware, the only study concerning resveratrol content in wine in the Balkan region was conducted in Greece. In this study, the trans- and cis-resveratrol content in samples obtained from 18 commercial Serbian wines (10 red, 7 white, and 1 rose) were analyzed. Analyses were performed after solid-phase extraction by high-performance liquid chromatography with a diode array detection system using an RP-C(18) column with gradient elution [solvent A: acetonitrile-acetic acid-water (20:2:78 v/v), solvent B: acetonitrile-acetic acid-water (90:2:8 v/v)]. Detection of trans- and cis-resveratrol was performed on 306 and 286 nm, respectively. It was clearly established that there was a presence of trans-resveratrol isomers in all analyzed wines (0.11-1.69 mg/L) except in one white wine. Cis-resveratrol was present in 12 from 18 samples in different amounts (0.12-1.49 mg/L).

A new approach to the compartmental analysis in pharmacokinetics: fractional time evolution of diclofenac.

This study presents a new two compartmental model and its application to the evaluation of diclofenac pharmacokinetics in a small number of healthy adults, during a bioequivalence trial. In the model the integer order derivatives are replaced by derivatives of real order often called fractional order derivatives. Physically that means that a history (memory) of a biological process, realized as a transfer from one compartment to another one with the mass balance conservation, is taken into account. This kind of investigations in pharmacokinetics is founded by Dokoumetzidis and Macheras through the one compartmental models while our contribution is the analysis of multi-dimensional compartmental models with the applications of the two compartmental model in evaluation of diclofenac pharmacokinetics. Two experiments were preformed with 12 healthy volunteers with two slow release 100 mg diclofenac tablet formulations. The agreement of the values predicted by the proposed model with the values obtained through experiments is shown to be good. Thus, pharmacokinetics of slow release diclofenac can be described well by a specific two compartmental model with fractional derivatives of the same order. Parameters in the model are determined by the least-squares method and the Particle Swarm Optimization (PSO) numerical procedure is used. The results show that the fractional order two compartmental model for diclofenac is superior in comparison to the classical two compartmental model. Actually this is true in general case since the classical one is a special case of the fractional one.

Solubilization of resveratrol in micellar solutions of different bile acids.

Bile acids are a special group of biological surfactants which can express different physiological and pharmacological effects. Micellar solutions of bile acids can solubilizate poorly soluble organic substances and improve their resorbtion. Above their critical micellar concentration (CMC) values, bile acids can cause interruption of membrane's integrity. Resveratrol (trans-3,5,4'-trihydroxystilbene) is a stilbene phytoalexine and studies reported that it can prevent or reduce diseases such as cancer and coronary heart disease. In this study, we examined affinity of different bile acids (CA, 12-MDCA, 12-MCA, 7-MCA, 7,12-DCA, 3,7,12-TCA) micellar solutions for resveratrol solubilization. CMC values for bile acids were determined by conductivity measurements. Concentration of micellar solutions were 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0 CMC value, for each acid respectively. At the same time, we investigated membranolytical potential of each acid. Solubilizated resveratrol was quantified using HPLC system with UV detection. Membranolytical potential was determined from citrate rabbit blood. Structures of mixed micelles of each bile acid and resveratrol were explained, and multiple linear regression equations for solubilization of resveratrol on different concentrations of bile acids were obtained. Micellar solution of 3,7,12-TCA had the biggest affinity for resveratrol solubilization and then, in decreasing order 7-MCA>7, 12-DCA>12-MCA>12-MDCA>CA. Also, 3,7,12-TCA had the lowest membranolytical potential.