Effect of grapefruit juice, naringin, naringenin, and bergamottin on the intestinal carrier-mediated transport of talinolol in rats

The effect of two varieties of grapefruit juice (white and ruby red) and its selected components (naringin, naringenin, and bergamottin) was investigated on the activity of the P-glycoprotein (P-gp) in male Sprague-Dawley rats. Talinolol, a nonmetabolized P-gp substrate, was used as a marker compound. The white grapefruit juice (GFJ) had a minor effect on talinolol pharmacokinetics, but the ruby red GFJ reduced the C max and the AUC (0-infinity) by 60% and 50% of the control, respectively. However, among the GFJ constituents tested, bergamottin (0.22 mg/kg) was the most potent component augmenting the C max and the AUC (0-infinity) of talinolol by 2.4- and 1.8-fold, respectively, if compared to the control group. The flavonoids naringenin (0.7 mg/kg) and naringin (2.4 and 9.4 mg/kg) had a similar effect increasing the talinolol C max and AUC (0-infinity) by 1.5- to 1.8-fold, respectively. In conclusion, the effect of GFJ on P-gp activity seems to depend on the variety, the concentration of compounds in the juice, and the composition of different ingredients.     

Pymetrozine,a Fast-Acting and Selective Inhibitor of Aphid Feeding. In-situ Studies with Electronic Monitoring of Feeding Behaviour

Pymetrozine, a pyridine azomethine compound, represents a novel insecticide with a selective activity against homopteran insects. It acts in a unique way: aphids are not knocked down on contact but seem to die of starvation. This implies an effect of pymetrozine on feeding behaviour. The aim of the present work was to elucidate how and at which step pymetrozine interferes with the complex mechanisms underlying phloem feeding. The effect of pymetrozine, applied in various ways, on different phases of stylet penetration and feeding activity of individual aphids was studied using the Electrical Penetration Graph technique (EPG). Initial choice experiments indicated that pymetrozine does not have a deterrent or antifeedant action. Topical application (150 ng pymetrozine mg^-1 fresh weight) inhibited stylet insertion into the plant. When injected, less than 30 ng mg^-1 was sufficient to produce the same effect. When pymetrozine was systemically applied via plant spraying or root uptake, aphids started feeding normally. After some time, however, they withdrew their stylets from the phloem and walked around with unaffected locomotion. At low doses aphids eventually recovered and resumed feeding. High doses, however, irreversibly disrupted feeding and prevented stylet reinsertion. Aphid motility was not affected up to an estimated haemolymph concentration of 1 mM pymetrozine. Aphids which eventually stopped feeding on pymetrozine-treated plants showed EPGs with distorted salivation/ingestion patterns. It is concluded that pymetrozine does not have a general toxic effect on aphids but selectively interferes with the nervous regulation of feeding behaviour which consequently results in death due to starvation after a few days. © 1997 SCI.     

Physiological and biochemical responses of two faba bean (Vicia faba L.) varieties grown in vitro to salt stress

Journal of Crop Science and Biotechnology - Faba bean (Vicia faba L.) is one of the most important legume crops worldwide. High salinity is a major constraint for faba bean productivity in many...     

Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum l.) polyphenols after ingestion of a standardized extract in healthy human volunteers

The intake of polyphenols has been demonstrated to have health-promoting and disease-preventive effects. The pomegranate (Punica granatum L.), which is rich in several polyphenols, has been used for centuries in ancient cultures for its medicinal purposes. The potential health benefits of pomegranate polyphenols have been demonstrated in numerous in vitro studies and in vivo experiments. This study investigated the absorption and antioxidant effects of a standardized extract from pomegranate in healthy human volunteers after the acute consumption of 800 mg of extract. Results indicate that ellagic acid (EA) from the extract is bioavailable, with an observed C(max) of 33 ng/mL at t(max) of 1 h. The plasma metabolites urolithin A, urolithin B, hydroxyl-urolithin A, urolithin A-glucuronide, and dimethyl ellagic acid-glucuronide were identified by HPLC-MS. The antioxidant capacity measured with the oxygen radical absorbance capacity (ORAC) assay was increased with a maximum effect of 32% after 0.5 h, whereas the generation of reactive oxygen species (ROS) was not affected. The inflammation marker interleukin-6 (IL-6) was not significantly affected after 4 h after the consumption of the extract. Overall, this study demonstrated the absorbability of EA from a pomegranate extract high in ellagitannin content and its ex vivo antioxidant effects.     

Variation of flavonoids and furanocoumarins in grapefruit juices: a potential source of variability in grapefruit juice-drug interaction studies

Grapefruit juice (GFJ) has been found to interact with several medications, increasing their oral bioavailability and the risk of toxicity. Inhibition of CYP3A4 in the small intestine by flavonoids (such as naringin and naringenin) and furanocoumarins (including bergamottin and 6',7'-dihydroxybergamottin) present in GFJ seems to be the predominant mechanism, although P-glycoprotein and influx transporters in the small intestine are also involved. The quantity of interactive compounds ingested may affect the magnitude and mechanism of the food-drug interaction. Therefore, these four compounds were quantified by HPLC analysis in commercially available and fresh-squeezed GFJ and in grapefruit tissues. Considerable variability in naringin (174-1492 micromol/L), bergamottin (1.0-36.6 micromol/L), and 6',7'-dihydroxybergamottin (0.22-52.5 micromol/L) was observed, whereas naringenin could not be detected. White grapefruit showed higher concentrations of naringin and furanocoumarins located in the albedo and flavedo compared with red varieties. Findings from this study suggest considering concentrations of components with a potential for drug interactions in GFJ-drug interaction studies. The concentration of potentially contributing compounds may crucially influence the magnitude of observed interaction and impair direct comparison of studies in which different juices have been used.     

Polymethoxylated flavones and other phenolic derivates from citrus in their inhibitory effects on P-glycoprotein-mediated transport of talinolol in Caco-2 cells

Many studies investigating drug interactions with citrus compounds focus on the major grapefruit furanocoumarins bergamottin, dihydroxybergamottin, and the flavonoid naringenin. This study evaluated the influence of polymethoxylated flavones (PMFs), tangeretin, nobiletin, 3,5,6,7,8,3,4'-heptamethoxyflavone, and sinensetin, as well as other minor occurring citrus phenols, hesperetin, limettin, 7-OH-coumarin, 7-geranyloxycoumarin, and eriodictyol, on P-glycoprotein-mediated transport of the beta-blocker talinolol using the Caco-2 cell monolayer model and was used to determine the structure-function aspects of the interaction. The transport of talinolol across Caco-2 cells monolayers was determined in the absence and presence of distinct concentrations of the calcium-channel blocker verapamil (a known inhibitor of P-glycoprotein) and citrus compounds. A sigmoid dose-response model was used to fit the data and to estimate the IC50 values of the potential inhibitors. Results from this study show that PMFs significantly decreased talinolol transport from the basolateral to apical side, where tangeretin had the lowest IC50 of 3.2 micromol/L, followed by nobiletin, heptamethoxyflavone, and sinensetin with IC50 values of 3.5, 3.8, and 3.9 micromol/L, respectively. However, the efficacy of the compounds did not appear to be dependent on the number of methoxy groups. Other citrus compounds did not have any significant effect on the transport of talinolol. This study suggests that PMFs have a high potential in the interaction with P-gp-mediated talinolol transport in Caco-2 cells. Based on their relatively low concentrations (< or =3 microg/mL) in citrus, the clinical relevance of these interactions needs to be further elucidated in in vivo studies.     

Glucosinolate concentration in turnip (Brassica rapa ssp. rapifera L.) roots as affected by nitrogen and sulfur supply

Three greenhouse pot experiments were conducted with four different nitrogen (N) treatments (80, 160, 240, and 320 kg ha (-1)) in combination with three sulfur (S) treatments (10, 20, and 60 kg ha (-1)) to study the effects of combined N and S supply on glucosinolate concentration and composition in turnip roots. Total glucosinolate concentration varied widely from 9.7 (N 320S 10) to 91.6 (N 160S 60) mg (100 g) (-1) root fresh weight (FW) and individual glucosinolate concentrations were increased with increasing S supply regardless of the N treatment, whereas enhanced N supply (160 - 320 N ha (-1)) at the high S level (60 kg ha (-1)) did not affect total glucosinolate concentration. In contrast, assumingly attributed to the individual glucosinolate biosynthesis concentration of N-containing tryptophan-derived indole glucosinolate was highest with increased N supply, whereas S-containing methionine-derived aromatic and aliphatic glucosinolates decreased with increasing N supply combined at low S level (10-20 kg ha (-1)).     

Constructed wetlands for the treatment of organic pollutants

Background  Constructed wetlands (wetland treatment systems) are wetlands designed to improve water quality. They use the same processes that occur in natural wetlands but have the flexibility of being constructed. As in natural wetlands vegetation, soil and hydrology are the major components. Different soil types and plant species are used in constructed wetlands. Regarding hydrology surface flow and subsurface flow constructed wetlands are the main types. Subsurface flow constructed wetlands are further subdivided into horizontal or vertical flow. Many constructed wetlands deal with domestic wastewater where BOD and COD (Biochemical and Chemical Oxygen Demand respectively) are used as a sum parameter for organic matter. However, also special organic compounds can be removed. Objective  The objectives are to summarise the state-of-the-art on constructed wetlands for treatment of specific organic compounds, to the present the lack of knowledge, and to derive future research needs. Methods  Case studies in combination with a literature review are used to summarise the available knowledge on removal processes for specific organic compounds. Results and Discussion  Case studies are presented for the treatment of wastewaters contaminated with aromatic organic compounds, and sulphonated anthraquinones, olive mill wastewater, landfill leachate, and groundwater contaminated with hydrocarbons, cyanides, chlorinated volatile organics, and explosives. In general the removal efficiency for organic contaminants is high in all presented studies. Conclusion  Constructed wetlands are an effective and low cost way to treat water polluted with organic compounds. There is a lack of knowledge on the detailed removal pathways for most of the contaminants. Removal rates as well as optimal plant species are substance-specific, and also typically not available. If a constructed wetland provides different environmental conditions and uses different plant species the treatment efficiency can be improved. Recommendations and Outlook  There is a great need to lighten the black box ‘constructed wetland’ to obtain performance data for both microbial activity and the contribution of the plants to the overall removal process. Also genetic modified plants should be considered to enhance the treatment performance of constructed wetlands for specific compounds.