Diana Marcela Aragón

Isolation of C-glycosylflavonoids with α-glucosidase inhibitory activity from Passiflora bogotensis Benth by gradient high-speed counter-current chromatography

In this study, we applied a gradient High-Speed Counter-Current Chromatography (HSCCC) method that allowed, by direct injection of an aqueous crude extract of the leaves of Passiflora bogotensis, the successful isolation of six flavonoids in a single run, with purity of each compound higher than 81%. This separation enabled the isolation of two new flavonoid glycosides, apigenin-6-C-α-l-rhamnopyranosyl-(1→2)-(6″-O-acetyl)-β-d-glucopyranoside (2) and luteolin-6-C-α-l-rhamnopyranosyl-(1→2)-(6″-O-acetyl)-β-d-glucopyranoside (4), and four known ones, isovitexin (1), isoorientin (3), isovitexin-2″-O-rhamnoside (5) and isoorientin-2″-O-rhamnoside (6). The structures of the isolated compounds were identified by HPLC-DAD, LC-MS, (1)H and (13)C NMR and comparison with literature data. The inhibitory activities of all of these compounds were evaluated in vitro on α-glucosidase from S. cerevisiae, and the IC50 was determinate. This is the first study concerning the chemical composition and biological activity of Passiflora bogotensis.

Thermodynamic study of the solubility of ibuprofen in acetone and dichloromethane

Thermodynamic functions, Gibbs energy, enthalpy and entropy for the solution processes of ibuprofen (IBP) in acetone and dichloromethane (DCM) were calculated from solubility values obtained at temperatures ranging from 293.15 K to 313.15 K. The respective thermodynamic functions for mixing and solvation processes as well as the activity coefficients for the solute were calculated. IBP solubility was high and proved similar in both solvents but was greater in DCM than acetone. In addition, the thermodynamic quantities for the transfer process of this drug from cyclohexane to the organic solvents were also calculated in order to estimate the contributions of hydrogen-bonds or of other dipolar interactions. The results were discussed in terms of solute-solvent interactions.

Solution thermodynamics of naproxen in some volatile organic solvents

The thermodynamic functions Gibbs energy, enthalpy and entropy for the solution processes of naproxen (NAP) in four volatile organic solvents were calculated from solubility values obtained at the temperature interval from 293.15 to 313.15 K. NAP solubility was determined in ethyl acetate, acetone, dichloromethane and acetonitrile, as pure solvents. The respective thermodynamic functions for mixing and solvation processes and the activity coefficients for the solute were also calculated. The NAP solubility decreases in the order, Acetone > AcOEt > DCM > AcNit. In addition, the thermodynamic quantities relative to the transfer process of this drug from cyclohexane to the organic solvents were also calculated in order to estimate the contributions due to hydrogen-bonding or other dipolar interactions. The results were discussed in terms of solute–solvent interactions.

Relationship between the solution thermodynamic properties of naproxen in organic solvents and its release profiles from PLGA microspheres

Naproxen (NPX)-loaded poly-(D,L-lactic-co-glycolic acid) (PLGA) microparticles were prepared by the emulsion–solvent evaporation method. The different organic solvents used significantly affects the properties of the microparticles obtained. These microparticles exhibited a controlled release profile that extends up to 15 days depending on the organic solvent used. The formulations did not exhibit zero- or first-order release kinetics and no agreement with Higuchi or Korsmeyer–Peppas models was obtained. In all cases, the dissolution profiles were fitted to the model proposed by Gallagher and Corrigan for PLGA systems. It was found that this model fully describes the dissolution processes. An interesting relationship between the NPX solubility in the organic solvents studied and some parameters obtained for the dissolution model of the microparticles prepared with the same solvents is thus obtained. Accordingly, it can be proposed that the drug solubility in organic solvents is relevant to estimate the physical characteristics of microparticles other than its dissolution profiles.

Biodistribution study of free and microencapsulated 6‐methylcoumarin in Wistar rats by HPLC

A sensitive, specific and reproducible HPLC method has been developed and validated for the quantitative determination of 6-methylcoumarin (6MC) in plasma and other tissues in Wistar rats. A C18 column was used with UV detection at 321 nm and a gradient system consisting of methanol-deionized water was used as mobile phase. The retention time for 6MC was 14.921 min and no interfering peaks were observed for any of the matrices. Linear relationships (r(2)  > 0.997) were obtained between the peak height ratios and the corresponding biological sample concentrations over the range 0.4-12.8 µg/mL. Precision and accuracy were evaluated; the coefficient of variation and the relative error for all of the organs were <2 and 7%, respectively. The limit of quantitation was 0.20 µg/mL for the heart and 0.30 µg/mL for the other tissues evaluated. This HPLC method was successfully used in the determination of 6MC in the biodistribution study after administration of 200 mg/kg of both 6MC-free and 6MC-loaded polymeric microparticles. In this study, extensive 6MC was found, in both free and microencapsulated forms, in all the organs tested. The 6MC-free showed a range of between 1.7 and 11.5 µg/g, while the microencapsulated 6MC showed concentrations of between 6.35 and 17.7 µg/g, suggesting that 6MC improved absorption rate.

Peruvioses A to F, sucrose esters from the exudate of Physalis peruviana fruit as α-amylase inhibitors

The fruit of Physalis peruviana is widely used in traditional Colombian medicine as an antidiabetic treatment. The aim of the study reported here was to identify the compounds responsible for the hypoglycemic activity using the α-amylase inhibition test. Bioguided fractionation of a dichloromethane extract of the sticky exudate that covers the fruit allowed the isolation and identification of three new sucrose esters, named as peruvioses C-E (1-3), along with the known peruvioses A (6), B (5) and F (4), the structures of which were elucidated by extensive NMR and MS experiments. These compounds proved to be responsible for the hypoglycemic activity observed in the extract. Peruviose D (2) showed the highest activity, with an inhibitory activity value of 84.8%. This is the first study to establish the potential of sucrose esters as α-amylase inhibitors and to explain the hypoglycemic effect that has traditionally been attributed to gooseberry fruit.

Pharmacokinetics of Botanical Drugs and Plant Extracts

BACKGROUND Botanical drugs contain plant extracts, which are complex mixtures of compounds. As with conventional drugs, it is necessary to validate their efficacy and safety through preclinical and clinical studies. However, pharmacokinetic studies for active constituents or characteristic markers in botanical drugs are rare. OBJECTIVE The objective of this review was to investigate the global state of the art in pharmacokinetic studies of active ingredients present in plant extracts and botanical drugs. A review of pharmacokinetics studies of chemical constituents of plant extracts and botanical drugs was performed, with a total of 135 studies published between January 2004 and February 2015 available in recognized scientific databases. Botanical preparations were mainly found in the form of aqueous extracts of roots and rhizomes. The most widely studied species was Salvia miltiorrhiza Bunge, and the compound most frequently used as a pharmacokinetic marker was berberine. CONCLUSION Most studies were performed using the Sprague Dawley rat model, and the preparations were mainly administered orally in a single dose. Quantification of plasma concentrations of pharmacokinetic markers was performed mainly by liquid-liquid extraction, followed by high performance liquid chromatography coupled to mass spectrometry detector. In conclusion, in recent years there has been an increasing interest among researchers worldwide in the study of pharmacokinetics of bioactive compounds in botanical drugs and plant extracts, especially those from the Traditional Chinese Medicine.