Asli Semiz

A Comparative Study for the Evaluation of Two Doses of Ellagic Acid on Hepatic Drug Metabolizing and Antioxidant Enzymes in the Rat

The present study was designed to evaluate different doses of ellagic acid (EA) in vivo in rats for its potential to modulate hepatic phases I, II, and antioxidant enzymes. EA (10 or 30 mg/kg/day, intragastrically) was administered for 14 consecutive days, and activity, protein, and mRNA levels were determined. Although the cytochrome P450 (CYP) 2B and CYP2E enzyme activities were decreased significantly, the activities of all other enzymes were unchanged with the 10 mg/kg/day EA. In addition, western-blot and qRT-PCR results clearly corroborated the above enzyme expressions. On the other hand, while the NAD(P)H:quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activities were increased significantly, CYP1A, 2B, 2C, 2E, and 19 enzyme activities were reduced significantly with 30 mg/kg/day EA. In addition, CYP2B, 2C6, 2E1, and 19 protein and mRNA levels were substantially decreased by the 30 mg/kg/day dose of EA, but the CYP1A protein, and mRNA levels were not changed. CYP3A enzyme activity, protein and mRNA levels were not altered by neither 10 nor 30 mg/kg/day ellagic acid. These results indicate that EA exerts a dose-dependent impact on the metabolism of chemical carcinogens and drugs by affecting the enzymes involved in xenobiotics activation/detoxification and antioxidant pathways.

Drug interaction potential of the seed extract of Urtica urens L. (dwarf Nettle)

Dwarf nettle (Urtica urens) seed extract was examined in vivo in the rat for its potential to modulate drug metabolizing enzymes including aminopyrine N‐demethylase (APND; CYP2C6), aniline 4‐hydroxylase (A4H; CYP2E1), nitrosodimethylamine N‐demethylase (NDMA‐ND; CYP2E1) erythromycin N‐demethylase (ERND; CYP3A1) CYP2D1/2 and glutathione S‐transferase (GST). RT‐PCR data and western blotting studies clearly demonstrated that CYP2C6 and CYP2E1 mRNA levels were substantially increased after Urtica treatment, while the level of CYP3A1 mRNA decreased and that of CYP2D1/2 remained unchanged. Urtica treatment significantly induced GST activity in the liver, lung and kidney (66‐, 46‐ and 31‐fold, respectively) while decreasing that of APND (35‐, 61‐ and 94‐fold) and NDMA‐ND (23, 28 and 54‐fold). ERND activity in liver was reduced 45‐fold, but increased in the lung and kidney (78‐ and 144‐fold) after Urtica treatment. These results indicate that Urtica seed extract may have the potential to inhibit and/or induce the metabolism of certain co‐administered drugs. Copyright

Essential oil composition, antioxidant activity and phenolic content of endemic Teucrium alyssifolium Staph. (Lamiaceae)

Abstract The present study was designed to examine the chemical composition of the essential oil, in vitro antioxidant activity and total phenolic and flavonoid content of extracts from plant parts (leaf, flower and stem) of Teucrium alyssifolium. The principle components of the essential oil were trans-β-caryophyllene (16.87%), ar-curcumene (11.43%) and bisabolene (11.06%), representing 39.36% of the oil. The total phenolic contents ranged between 13.99 and 41.54 mg of GAE/g of extract. The concentrations of flavonoids varied from 16.82 to 49.52 mg of Ru/g of extract. Antioxidant activity was determined in vitro using DPPH reagent and expressed as concentration of each extract required to inhibit radical by 50% (IC50) values that ranged from 13.52 to 132.55 μg/ml. Our results have indicated that water extract of T. alyssifolium (part leaf) with a total content of polyphenols (41.54 mg of GAE/g) and an IC50 of 13.52 μg/ml is more antioxidant.

Epilobium hirsutum alters xenobiotic metabolizing CYP1A1, CYP2E1, NQO1 and GPx activities, mRNA and protein levels in rats.

Abstract Context: Natural products have attracted increasing interests due to their use in flavoring, nutrition, cosmetics, pharmacy and medicine. Epilobium hirsutum L. (Onagraceae) is known for its analgesic, antimicrobial, and antiproliferative activity. CYP1A1 and CYP2E1, xenobiotic metabolizing enzymes, serve as a metabolic activation route yielding reactive metabolites that are eliminated by the action of NQO1 and glutathione peroxidase (GPx) enzymes. Objective: This study investigated in vivo effects of Epilobium hirsutum (EH) on CYP2E1, CYP1A1, NQO1 and GPx activities, protein and mRNA expressions in liver. Materials and methods: Male Wistar Albino rats were injected with EH at a dose of 37.5 mg/kg i.p. daily for 9 d. CYP2E1, CYP1A1, NQO1 and GPx activities, protein and mRNA levels were determined by enzyme assays, Western blotting and qPCR, respectively. Results: CYP1A1 associated ethoxyresorufin-O-deethylase activity of control and EH-treated animals were found as 6.54 ± 1.21 and 4.48 ± 1.67 nmol/min/mg, respectively. CYP2E1 associated aniline 4-hydroxylase of control and EH group were 0.537 ± 0.011 and 0.109 ± 0.01 nmol/min/mg, respectively. However, EH treatment increased the GPx and NQO1 activities from 0.069 ± 0.015 to 0.107 ± 0.026 nmol/min/mg and from 163.34 ± 92 to 588.3 ± 14 nmol/min/mg, respectively. Furthermore, protein and mRNA expression analysis revealed that CYP1A1 and CYP2E1 levels were decreased while those of NQO1 and GPx increased after EH treatment. Discussion and conclusion: Our current data suggest that the metabolism of xenobiotics, including drugs, may be altered due to changes in the expression and activity of these proteins by EH.

Alteration of drug metabolizing enzymes in sulphite oxidase deficiency

The aim of this study was to investigate the possible effects of sulphite oxidase (SOX, E.C. 1.8.3.1) deficiency on xenobiotic metabolism. For this purpose, SOX deficiency was produced in rats by the administration of a low molybdenum diet with concurrent addition of 200 ppm tungsten to their drinking water. First, hepatic SOX activity in deficient groups was measured to confirm SOX deficiency. Then, aminopyrine N-demethylase, aniline 4-hydroxylase, aromatase, caffeine N-demethylase, cytochrome b5 reductase, erythromycin N-demethylase, ethoxyresorufin O-deethylase, glutathione S-transferase, N-nitrosodimethylamine N-demethylase and penthoxyresorufin O-deethylase activities were determined to follow changes in the activity of drug metabolizing enzymes in SOX-deficient rats. Our results clearly demonstrated that SOX deficiency significantly elevated A4H, caffeine N-demethylase, erythromycin N-demethylase and N-nitrosodimethylamine N-demethylase activities while decreasing ethoxyresorufin O-deethylase and aromatase activities. These alterations in drug metabolizing enzymes can contribute to the varying susceptibility and response of sulphite-sensitive individuals to different drugs and/or therapeutics used for treatments.

Contribution of ellagic acid on the antioxidant potential of medicinal plant Epilobium hirsutum

abstract In the present study, the possible role of ellagic acid (EA) on antioxidant potential of Epilobium hirsutum (EH) in rat liver was investigated. Wistar rats were intraperitoneally treated with 37.5 mg/kg of EH and 10 mg/kg of EA for 9 days. Effects of EH and EA on antioxidant [glutathione peroxidase (GPx) and superoxide dismutases (SOD)] and Phase II [NADPH quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTs)] enzyme activities, as well as protein and mRNA expressions of those, were investigated. Polyphenolic content of EH was determined by LC-MS/MS analysis. EH and EA injection to rats resulted in a significant increase of NQO1 (3.6-fold and 4.7-fold), GPx (1.45-fold), and SOD (1.34-fold and 1.27-fold) enzyme activities, whereas total GST (46% and 57%) and its isoforms,and GST mu (57% and 72%), and GST theta (60% and 68%) activities were significantly decreased. Western-blot and qRT-PCR analysis showed that NQO1 and GPx protein and mRNA expressions were increased significantly (P < 0.0001), whereas GST mu and GST theta were significantly decreased (P < 0.0001).

Essential oil composition, total phenolic content, antioxidant and antibiofilm activities of four Origanum species from southeastern Turkey

ABSTRACT This study reports a comparative screening of four species of Origanum in Turkey, based on their essential oil composition, total phenolic content, antioxidant and antibiofilm activities. The major components of essential oils were p-cymene, linalool, and thymol. The total phenolic contents differed from 3.81 to 47.54 mg of GAE/g of extract. The concentrations of flavonoids varied from 12.74 to 58.39 mg of Ru/g of extract. Antioxidant activity was determined in vitro using DPPH reagent and expressed as concentration of each extract required to inhibit radical by 50% (IC50) values that ranged from 16.03 to 48.94 μg/ml. Our results indicated that chloroform extracts of species O. majorana and O. onites, with a total content of polyphenols (47.54 mg of GAE/g and 45.17 mg of GAE/g, respectively) and an IC50 of 16.03 μg/ml and 16.89 μg/ml, respectively were more antioxidant. Among the essential oil concentrations tested, maximum antibiofilm activity was found as 92.24% against M. luteus NRRL-B 1013 by O. majorana essential oil at 50 mg/ml.