Jelena B. Zvezdanović

The estimation of the traditionally used yarrow (Achillea millefolium L. Asteraceae) oil extracts with anti-inflamatory potential in topical application

ETHNOPHARMACOLOGICAL RELEVANCE Olive or sunflower oil yarrow extracts have been extensively used against inflammatory disorders and skin wound healing in traditional medicine. AIM OF THE STUDY To evaluate oil yarrow extracts traditional use in treatment of topical/dermatological skin impairments, sodium lauryl sulfate test was applied, and in vivo measuring of the biophysical parameters (erythema index, skin capacitance and the pH of the skin) in the artificially irritated skin was performed. As traditionally olive and sunflower oil have been used equally for extracts production, the experiment was carried out to investigate whether any of the oil extractants has the advantage over the other, and if the method of extraction might influence the desired activity. The observed activity has been connected to the chemical profile of the investigated extracts and their antioxidative properties. MATERIALS AND METHODS In vivo measurements were performed using the appropriate probes for measuring skin capacitance, pH of the skin and erythema index (EI). The designed experiment enabled the evaluation of the anti-inflammatory effects of a seven-day application of oil yarrow extracts known in traditional medicine, on artificially irritated skin of volunteers. The chemical profile for the investigated samples was achieved applying the HPLC and UHPLC-MS methods. Also, ferric reducing antioxidant power (FRAP) test was performed to assess the antioxidant properties of the investigated samples. RESULTS The application of tested oil extracts on artificially irritated skin in vivo demonstrated the ability to re-establish their optimal pH and hydration of skin to the values measured prior to the irritation. Considering the EI transition, the investigated samples succeeded in re-establishing the baseline values, with no significant difference after three- and seven-day application. CONCLUSIONS The data obtained in the study showed that the oil yarrow extracts had an evident anti-inflammatory property. Namely, the investigated extracts demonstrated significant anti-inflammatory effect in an in vivo double blind randomized study, using a sodium lauryl sulfate test. The skin parameters assessed in the study (skin capacitance, pH and EI) were restored to the basal values after three- and seven-day treatment with the tested extracts. The shown effects were attributed to yarrow oil extracts composition. The yarrow oil extracts might be used as promising base in the phytopreparations designed for dermatological application as anti-inflammatory agents with a positive impact on the skin pH and its moisture content.

P-Glycoprotein Polymorphism C3435T Is Associated with Dose-Adjusted Clopidogrel and 2-Oxo-Clopidogrel Concentration

Background/Aims: One of the most common polymorphisms of ABCB1 gene, a synonymous mutation C3435T (rs1045642), is associated with increased in vivo activity. The main goal of this study was to determine the association of C3435T polymorphism with clopidogrel and 2-oxo-clopidogrel concentrations in plasma. Methods: The patients were recruited upon acute myocardial infarction diagnosis. They were all tested for ABCB1 C3435T polymorphism. In plasma, drawn 1 h after the drug administration, concentrations of clopidogrel and 2-oxo-clopidogrel were measured using UHPLC-DAD-MS analysis. Results: Due to differences in the maintenance doses, we have calculated the dose-adjusted concentrations of clopidogrel (0.2 ng/ml/mg (0.1-0.4)) and 2-oxo-clopidogrel (2.1 ng/ml/mg (0.5-4.6)). Patients carrying at least one C allele achieved significantly higher serum concentration of clopidogrel (p < 0.001), as well as dose-adjusted clopidogrel (p < 0.001) and 2-oxo-clopidogrel concentrations (p < 0.05). Conclusion: The ABCB1 3435CC genotype is associated with increased clopidogrel and 2-oxo-clopidogrel dose-adjusted concentrations. Therefore, the ABCB1 C3435T genotyping should be one of the parameters taken into account when deciding about the dosing regimen of clopidogrel.

Benzophenone Suppression of Quercetin Antioxidant Activity towards Lipids under UV-B Irradiation Regime: Detection by HPLC Chromatography

Quercetin, a well-known flavonoid antioxidant, has been employed to control benzophenone-sensitized peroxidation of the lipid mixture in methanol solution, induced by continuous UV-B irradiation. Surprisingly, the detected quercetin antioxidant activity was almost negligible. The presented data suggests that the reason is not in its own UV-B-induced degradation but rather in its interrelationship with benzophenone during UV-B stress. On the other side of this relationship, benzophenone anticipated sensitizing role towards lipids; that is, the initiation of lipid peroxidation has been affected as well. These results, obtained by HPLC chromatography, partly confirm but partly relativize to some extent recent results obtained with the same system by spectrophotometric method.

Quercetin degradation induced by continuous UV-B irradiation in the presence of benzophenone

ion from lipids by triplet states of derivatized benzophenone photosensitizers, Photochemistry and Photobiology, 51(4) (1990) 389 394. [9] D. Z. Marković, L. K. Patterson, Radical processes in lipids. Selectivity of hydrogen abstraction from lipids by benzophenone triplet, Photochemistry and Photobiology, 49(5) (1989) 531 535. [10] D. Z. Marković, L. K. Patterson, Benzophenone-sensitized lipid peroxidation in linoleate micelles, Photochemistry and Photobiology, 58(3) (1993) 329 334. [11] A. Beckett, B. McClure, K. Zimmerman, Benzophenone and padimate-O protect Saccharomyces cerevisiae from UV radiation and cause little harm from UV-induced reactive chemical species, Journal of Experimental Microbiology and Immunology, 5 (2004) 37 43. [12] F. Zhang, J. Zhang, C. Tong, C. Yadong, Z. Shulin, L. Weiping Molecular interactions of benzophenone UV filters with humanserum albumin revealed by spectroscopic techniques and molecular modeling, Journal of Hazardous Materials, 263(Part 2) (2013) 618 626. [13] A. R. Ndhlala, M. Moyo, J. V. Staden, Natural antioxidants: fascinating or mythical biomolecules?, Molecules, 15(10) (2010) 6905 6930. [14] S. Tahara, A journey of twenty-five years through the ecological biochemistry of flavonoids, Bioscience, Biotechnology and Biochemistry, 71(6) (2007) 1387 1404. [15] A. Saija, A. Tomaino, D. Trombetta, M. L. Pellegrino, B. Tita, C. Messina, F. P. Bonina, C. Rocco, G. Nicolosi, F. Castelli, ”In vitro” antioxidant and photoprotective properties and interaction with model membranes of three new quercetin esters, European Journal of Pharmaceutics and Biopharmaceutics, 56(2) (2003) 167 174. [16] U. J. Joshi, A. S. Gadge, P. D’Mello, R. Sinha, S. Srivastava, G. Govil, Anti-inflammatory, antioxidant and anticancer activity of quercetin and its analogues, International Journal of Research in Pharmaceutical and Biomedical Sciences, 2(4) (2011) 1756 1766. [17] E. Falkovskaia, P. K. Sengupta, M. Kasha, Photophysical induction of dual fluorescence of quercetin and related hydroxyflavones upon intermolecular H-bonding to solvent matrix, Chemical Physics Letters, 297(1-2) (1998) 109 114. [18] B. M. Fahlman, E. S. Krol, UVA and UVB radiation-induced oxidation products of quercetin, Journal of Photochemistry and Photobiology B: Biology, 97(3) (2009) 123 131. [19] A. Zhou, O. A. Sadik, Comparative analysis of quercetin oxidation by electrochemical, enzymatic, autoxidation, and free radical generation techniques: a mechanistic study, Journal of Agricultural Food Chemistry, 56(24) (2008) 12081 12091. [20] F. T. M. C. Vicentini, S. R. Georgetti, J. R. Jabor, J. A. Caris, M. V. L. B. Bentley, M. J. V. Fonseca, Photostability of quercetin under exposure to UV irradiation, Latin American Journal of Pharmacy, 26(1) (2007) 119 124. [21] S. Dall’Acqua, G. Miolo, G. Innocenti and S. Caffieri, The photodegradation of quercetin: relation to oxidation, Molecules, 17(8) (2012), 8898 8907. [22] A. Marfak, P. Trouillas, D. P. Allais, C. A. Calliste and J. L. Duroux, Redox reactions obtained by gamma irradiation of quercetin methanol solution are similar to in vivo metabolism, Radiation Research, 159(2) (2003) 218 227. [23] A. Zhou, S. Kikandi, O. A. Sadik, Electrochemical degradation of quercetin: Isolation and structural elucidation of the degradation products, Electrochemistry Communications, 9(9) (2007) 2246 2255. [24] A. K. Timbola, C. D. de Souza, C. Giacomelli, A. Spinelli, Electrochemical oxidation of quercetin in hydro-alcoholic solution, Journal of the Brazilian Chemical Society, 17(1)

Riboflavin degradation in the presence of quercetin in methanol under continuous UV-B irradiation: the ESI–MS–UHPLC analysis

The presented work deals with continuous UV-B irradiation of riboflavin in MeOH solution, leading to its degradation under anaerobic as well as aerobic conditions (faster in the former case), which is related to riboflavin photosensitizing properties (type I photosensitizer in the first case, and type II in the other one). Addition of quercetin, a well-known antioxidant in the system causes a decrease of the (riboflavin) degradation in both cases. In anaerobic conditions it might be a consequence of quercetin antioxidant scavenging activity, while under aerobic conditions it could be related to singlet oxygen formation. The degradation dynamics—in both systems, in the presence and in the absence of quercetin—is well synchronized with dynamics formation of the two major products, lumiflavin and lumichrome.Graphical abstract