Population Pharmacokinetic Modeling to Inform Sertraline Dosing Optimization in Patients with Depression.

Sertraline is one of the most prescribed antidepressants, but its pharmacokinetic (PK) properties are still not completely characterized. Using nonlinear mixed-effects modeling, we examined factors influencing sertraline PK variability in outpatients with major depressive disorder. Blood samples from 53 male and female adults treated with sertraline orally were collected at a steady state. Various demographic and clinical covariates were tested by stepwise regression procedure. We found that sertraline clearance is significantly influenced by serum concentrations of its main metabolite N-desmethylsertraline, whereas clearance of N-desmethylsertraline is affected by both creatinine clearance and drug daily dose. These results were confirmed by the reduction of points dispersion in goodness-of-fit plots for their predicted versus measured concentrations and with bootstrapping analyses. This finding can serve to inform sertraline dosing optimization, especially when changes in kidney function occur in treated individuals, to prevent adverse drug reactions and maximize therapeutic benefits.

Comparison of Polyphenol-Enriched Tomato Juice and Standard Tomato Juice for Cardiovascular Benefits in Subjects with Stage 1 Hypertension: a Randomized Controlled Study.

There is a growing body of evidence that tomato consumption reduces the risk of cardiovascular disease, through antioxidative, anti-inflammatory and hypotensive effects. We compared the effects of polyphenol-enriched and standard tomato juice on parameters of lipid and oxidative status and blood pressure in subjects with stage 1 hypertension. The experimental group (n = 13) was supplemented with 200 g of tomato fruit juice enriched with 1 g of ethanolic extract of whole tomato fruit, while the control group (n = 13) was consuming 200 g tomato fruit juice. Before and after the treatment, blood samples were collected, and blood pressure was measured. Markers of oxidative stress and antioxidative defense: paraoxonase (PON1), thiobarbituric acid reactive substances (TBARS), total antioxidant status (TAS), total oxidant status (TOS), pro-oxidant-antioxidant balance (PAB) and C reactive protein (CRP) were determined in serum. Prothrombin time (PT) was measured in the whole blood samples. Parameters of lipid status, as well as susceptibility to copper-induced oxidation of LDL particles in vitro were also determined. There was a significant reduction in total cholesterol and LDL-C only in the control group at the end of the study. No significant differences were observed in the remainder of the assessed parameters along the study. In conclusion, tomato juice may have favorable effects on lipid metabolism, but polyphenol fortification does not constitute additional beneficial cardiovascular effects.

Negligible adsorption and toxicity of microplastic fibers in disinfected secondary effluents.

Wastewater treatment plants play a crucial role in controlling the transport of pollutants to the environment and often discharge persistent contaminants such as synthetic microplastic fibers (MFs) to the ecosystem. In this study, we examined the fate and toxicity of polyethylene terephthalate (PET) MFs fabricated from commercial cloth in post-disinfection secondary effluents by employing conditions that closely mimic disinfection processes applied in wastewater treatment plants. Challenging conventional assumptions, this study illustrated that oxidative treatment by chlorination and ozonation incurred no significant modification to the surface morphology of the MFs. Additionally, experimental results demonstrated that both pristine and oxidized MFs have minimal adsorption potential towards contaminants of emerging concern in both effluents and alkaline water. The limited adsorption was attributed to the inert nature of MFs and low surface area to volume ratio. Slight adsorption was observed for sotalol, sulfamethoxazole, and thiabendazole in alkaline water, where the governing adsorption interactions were suggested to be hydrogen bonding and electrostatic forces. Acute exposure experiments on human cells revealed no immediate toxicity; however, the chronic and long-term consequences of the exposure should be further investigated. Overall, despite the concern associated with MFs pollution, this work demonstrates the overall indifference of MFs in WWTP (i.e., minor effects of disinfection on MFs surface properties and limited adsorption potential toward a mix of trace organic pollutants), which does not change their acute toxicity toward living forms.

Analysis of antioxidant potential of fruit and vegetable juices available in Serbian markets.

Antioxidants in fruit and vegetable juices have become increasingly popular because of their potential health benefits. Nowadays, juice mixes made from berries present frequent consumer choices, due to their nutritive value and high content of bioactive compounds. Commercial fruit and vegetable juices available in Serbian markets (n = 32) were analyzed for the physicochemical properties, chemical composition, and antioxidant activity. Relative antioxidant capacity index was used for the ranking of the juices according to antioxidant capacity, while antioxidant effectiveness of phenolic compounds contained in juice samples was investigated depending on phenolic antioxidant coefficients. Principal component analysis was applied to study the data structure. In addition, a multi-layer perceptron model was used for modeling an artificial neural network model (ANN) for prediction antioxidant activity (DPPH, reducing power, and ABTS) based on total phenolic, total pigments, and vitamin C content. The obtained ANN showed good prediction capabilities (the r2 values during training cycle for output variables were 0.942). Phenolic, pigments, and vitamin C contents showed a positive correlation with the investigated antioxidant activity. The consumption of commercial berry fruit juices available in Serbian markets may deliver great health benefits through the supply of natural antioxidants.

UHPLC-Triple-TOF-MS Characterization, Antioxidant, Antimicrobial and Antiproliferative Activity of Raspberry (Rubus idaeus L.) Seed Extracts.

The primary aim of this experiment was to investigate the bioactivity potential and polyphenolic profile of defatted raspberry seeds (DRS) extracts from three varieties (Willamette, Meeker, and Polka) using the in vitro tests HPLC-DAD and UHPLC-Triple-TOF-MS. Extracts were obtained using ultrasound-assisted extraction (UAE) or hydrolysis. The antioxidant activity of the extracts was tested using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic) cation (ABTS), and ferric reducing antioxidant power (FRAP) assays. Furthermore, the extracts were tested for antimicrobial activity using the disk diffusion method for four bacterial cultures (Staphylococcus aureus, Escherichia coli, Listeria monocytogenes, and Salmonella enterica subsp. enterica Enteritidis). In vitro antiproliferative activity was tested using cervical carcinoma (HeLa), breast adenocarcinoma (MCF7), and fetal lung (MRC-5) human cell lines. In total, 32 phenolic compounds were detected in DRS extracts. A small quantity of ellagic acid (EA) was in free form, while EA content increased after the hydrolysis process. The extracts from the Meeker variety exhibited the highest antioxidant activity, analyzed with DPPH and FRAP assays, while extracts from the Polka variety had the highest activity towards ABTS•+ radical scavenging activity. The UAE samples expressed higher antiproliferative activity in comparison to hydrolysis extracts. The results indicate that DRS extracts have certain bioactivity, and their use in the food, cosmetic, and pharmaceutical industries is recommended.

Textural, Color and Sensory Features of Spelt Wholegrain Snack Enriched with Betaine.

The influence of different extrusion parameters, including screw speed (250-750 rpm), feed rate (15-25 kg/h) and feed moisture content (15-25%), on the textural and color properties of spelt wholegrain snack products produced on a co-rotating twin-screw extruder with added betaine was investigated. In order to determine the relative influence of input variables in the artificial neural network (ANN) model, Yoon's interpretation method was used, and it was concluded that feed moisture content has the greatest influence on L* values, while screw speed has the greatest influence on a* and b* values. The softest samples were obtained at the lowest moisture content. Sensory analysis was carried out on selected samples, and it showed that betaine addition did not intensify the bitter taste. The sample with the largest expansion exhibited the lowest hardness and chewiness before and after immersion in milk, and this sample is the most suitable for enrichment with betaine.

Development of a Novel Rice-Based Snack Enriched with Chicory Root: Physicochemical and Sensory Properties.

A novel rice-based snack enriched with chicory root flour (CRF) was developed by twin-screw extrusion. Chicory (Cichorium intybus L.) is one of the promising medicinal plants for the development of innovative food and may be considered a functional food ingredient. Central composite design (CCD) was employed to generate snack formulations by varying feed moisture (M, 16.3-22.5%), screw speed (SS, 500-900 rpm) and CRF content (20-40%). The optimization according to artificial neural network modeling and a genetic algorithm was applied to define optimal process conditions (17.6% moisture, 820 rpm and 24.1% of CRF) for obtaining the product with the highest expansion (3.34), crispiness (3.22 × 10-3), volume (2040 m3), degree of gelatinization (69.70%) and good color properties. Bulk density (110.33 g/L), density (250 kg/m3), and hardness (98.74 N) resulted in low values for the optimal sample. The descriptive sensory analysis evaluated low hardness and bitterness, with high crispiness for the optimal extrudate. This study points to the possibility of a novel chicory enriched extrudate production with desirable physicochemical and sensory properties.

Chicory (Cichorium intybus L.) as a food ingredient - Nutritional composition, bioactivity, safety, and health claims: A review.

Chicory (Cichorium intybus L.) is a perennial herb from the Cichorium genus, Asteraceae family, and is worldwide cultivated. So far, chicory has been used mainly in animal feed, but also in several cases in the food industry: as salad, for teas and tea blends, for coffee supplementation, and as a source for the inulin production. Nowadays there is an increasing interest in chicory utilization for food production and supplementation. Some compounds present in chicory, such as polyphenols, inulin, oligofructose and sesquiterpene lactones may be considered as potential carriers of food functionality. This review describes nutritional, mineral and bioactive composition of the chicory plant and summarized the main biological activities associated with the presence of bioactive compounds in the different plant parts. Finally, the review explores possibilities of uses of chicory and its implementation in food products, with intention to design new functional foods.

pH-Responsive Release of Ruthenium Metallotherapeutics from Mesoporous Silica-Based Nanocarriers.

Ruthenium complexes are attracting interest in cancer treatment due to their potent cytotoxic activity. However, as their high toxicity may also affect healthy tissues, efficient and selective drug delivery systems to tumour tissues are needed. Our study focuses on the construction of such drug delivery systems for the delivery of cytotoxic Ru(II) complexes upon exposure to a weakly acidic environment of tumours. As nanocarriers, mesoporous silica nanoparticles (MSN) are utilized, whose surface is functionalized with two types of ligands, (2-thienylmethyl)hydrazine hydrochloride (H1) and (5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)hydrazine (H2), which were attached to MSN through a pH-responsive hydrazone linkage. Further coordination to ruthenium(II) center yielded two types of nanomaterials MSN-H1[Ru] and MSN-H2[Ru]. Spectrophotometric measurements of the drug release kinetics at different pH (5.0, 6.0 and 7.4) confirm the enhanced release of Ru(II) complexes at lower pH values, which is further supported by inductively coupled plasma optical emission spectrometry (ICP-OES) measurements. Furthermore, the cytotoxicity effect of the released metallotherapeutics is evaluated in vitro on metastatic B16F1 melanoma cells and enhanced cancer cell-killing efficacy is demonstrated upon exposure of the nanomaterials to weakly acidic conditions. The obtained results showcase the promising capabilities of the designed MSN nanocarriers for the pH-responsive delivery of metallotherapeutics and targeted treatment of cancer.

Methanol Sensing by a Luminescent Zinc(II)-Based Metal-Organic Framework.

A luminescent zinc-based metal-organic framework (MOF; 1) was synthesized from a highly conjugated tridentate ligand, 1,3,5-tris[(1E)-2'-(4''-benzoic acid)vinyl]benzene. X-ray single crystal analysis reveals the organization of 1 in a three-dimensional porous framework. Thermogravimetric analysis shows that 1 has a good thermal stability, and resists decomposition up to 420 °C. The removal of the solvent molecules from the cavities leads to a temporary loss of crystallinity, which can be regained by heating the MOF in diethylformamide, the solvent used for the synthesis, as shown by powder X-ray diffraction. In addition, 1 shows luminescent features influenced by the chemical environment, making it suitable as optical sensor. Detection of methanol with a turn-on effect was possible in low concentration in mixtures with water (50 µL/3 mL and 10 µL/3 mL) and as vapor.

Phytoecdysteroids increase protein synthesis in skeletal muscle cells.

Phytoecdysteroids, which are structurally similar or identical to insect molting hormones, produce a range of effects in mammals, including increasing growth and physical performance. To study the mechanism of action of phytoecdysteroids in mammalian tissue, an in vitro cellular assay of protein synthesis was developed. In C2C12 murine myotubes and human primary myotubes, phytoecdysteroids increased protein synthesis by up to 20%. In vivo, ecdysteroids increased rat grip strength. Ecdysteroid-containing plant extracts produced similar results. The effect was inhibited by a phosphoinositide kinase-3 inhibitor, which suggests a PI3K-mediated mechanism.

Betaine in Cereal Grains and Grain-Based Products.

Betaine is a non-essential nutrient which performs several important physiological functions in organisms. Abundant data exist to suggest that betaine has a potential for prevention of chronic diseases and that its dietary intake may contribute to overall health enhancement. Several studies have pointed out that the betaine status of the general population is inadequate and have suggested nutritional strategies to improve dietary intake of betaine. Cereal-based food has been implicated as the major source of betaine in the Western diet. This review summarizes the results on the betaine content in various cereals and related products. Attention has been given to the betaine content in gluten-free grains and products. It also discusses the stability of betaine during processing (cooking, baking, extrusion) and possibilities to increase betaine content by fortification.

Mesoporous Silica and Organosilica Nanomaterials as UV-Blocking Agents.

Mesoporous silica nanoparticles (MSN) and periodic mesoporous organosilica nanoparticles containing bridging benzene (PMOBTB) and ethane (PMOBTE) moieties are synthesized, characterized, and evaluated for application in skin protection from UVA/UVB sun irradiation. Furthermore, the influence of surface functionalization with chelating 3-(2-aminoethylamino)propylsilane and Zn2+ ions on the UV-blocking ability of MSN is evaluated, along with the photostability and capability of the synthesized nanomaterials to carry avobenzone, a known UV-absorbing agent. The obtained results reveal promising characteristics of MSN and PMO materials with regard to their potential for sunscreen applications, which could be beneficial in terms of alleviating concerns about health and environmental hazards of sunscreen ingredients.

Toxicological evaluation of a chicory root extract.

An Ames test and a 28-day sub-chronic toxicity study in male and female Sprague-Dawley rats were conducted to evaluate the safety of a chicory root extract being investigated as a therapeutic for inflammation. Chicory extract had no mutagenic activity in the Ames test although it was cytotoxic to certain strains of Salmonella at higher doses with and without metabolic activation. For the 28-day rat study, measurements included clinical observations, body weights, food consumption, clinical pathology, gross necropsy and histology. There were no treatment-related toxic effects from chicory extract administered orally at 70, 350, or 1000 mg/kg/day. Since there were no observed adverse effects of chicory extract in these studies, the NOAEL for the extract is 1000 mg/kg/g administered orally for 28 days.

Effects of Arachis hypogaea nutshell extract on lipid metabolic enzymes and obesity parameters.

The aim of the present study was to assess the effects of peanut (Arachis hypogaea L.) shell extracts (PSE) on lipases and to evaluate its potential development for the treatment of obesity. The peanut shells were extracted in 95% ethanol, and the extracts were screened for inhibitory effects on pancreatic lipase (PL) and lipoprotein lipase (LPL) activities as well as on lipolysis of 3T3-L1 adipocytes. We also examined in vivo whether PSE could prevent the body weight gain induced by feeding a high-fat diet to male Wistar rats for 12 weeks. PSE inhibits a number of lipases, including PL, LPL and, possibly, hormone sensitive lipase (HSL). PSE-treated Wistar rats showed increased fecal lipid excretion respect to the control group. Body weight and body weight gain, and liver size, were significantly lower in rats fed the high-fat diet with 1% of PSE (w:w diet) than in those fed the high-fat diet alone. The rats treated with PSE showed reduced triacylglycerol content in the liver, as well as the serum glucose and insulin. The inhibitory activity of PSE on the lipid metabolic enzymes and the increase in fecal fat excretion suggests that PSE might be useful as a treatment to reduce the dietary fat absorption. The observed reduction in intracellular lipolytic activity of cultured 3T3-L1 adipocytes may reduce the levels of circulating free fatty acids. The observed effects are likely induced by more than one bioactive component of PSE. The PSE actions may, at least in part, be attributed to the inhibition of fat absorption in the digestive tract and the reduction of the adipocyte lipolysis.

Plants and human health in the twenty-first century.

The concept of growing crops for health rather than for food or fiber is slowly changing plant biotechnology and medicine. Rediscovery of the connection between plants and health is responsible for launching a new generation of botanical therapeutics that include plant-derived pharmaceuticals, multicomponent botanical drugs, dietary supplements, functional foods and plant-produced recombinant proteins. Many of these products will soon complement conventional pharmaceuticals in the treatment, prevention and diagnosis of diseases, while at the same time adding value to agriculture. Such complementation can be accelerated by developing better tools for the efficient exploration of diverse and mutually interacting arrays of phytochemicals and for the manipulation of the plant's ability to synthesize natural products and complex proteins. This review discusses the history, future, scientific background and regulatory issues related to botanical therapeutics.

Inhibitory effects of grape seed extract on lipases.

OBJECTIVE: The aim of the present study was to assess the effects of grape seed extract (GSE) on the fat-metabolizing enzymes pancreatic lipase, lipoprotein lipase, and hormone-sensitive lipase in vitro and evaluate its potential application as a treatment for obesity. METHODS: Crushed grape seeds were extracted in ethanol, and the extract was assayed for the measurement of inhibitory effects on pancreatic lipase and lipoprotein lipase activities and on lipolysis of 3T3-L1 adipocytes. RESULTS: The GSE rich in bioactive phytochemicals showed inhibitory activity on the fat-metabolizing enzymes pancreatic lipase and lipoprotein lipase, thus suggesting that GSE might be useful as a treatment to limit dietary fat absorption and the accumulation of fat in adipose tissue. The observed reduction in intracellular lipolytic activity of cultured 3T3-L1 adipocytes may reduce the levels of circulating free fatty acids that have been linked to insulin resistance in obese patients. CONCLUSION: The GSE rich in compounds that inhibit lipases may provide a safe, natural, and cost-effective weight control treatment.

Anti-inflammatory activity of grains of paradise (Aframomum melegueta Schum) extract.

The ethanolic extract of grains of paradise (Aframomum melegueta Schum, Zingiberaceae) has been evaluated for inhibitory activity on cyclooxygenase-2 (COX-2) enzyme, in vivo for the anti-inflammatory activity and expression of several pro-inflammatory genes. Bioactivity-guided fractionation showed that the most active COX-2 inhibitory compound in the extract was [6]-paradol. [6]-Shogaol, another compound from the extract, was the most active inhibitory compound in pro-inflammatory gene expression assays. In a rat paw edema model, the whole extract reduced inflammation by 49% at 1000 mg/kg. Major gingerols from the extract [6]-paradol, [6]-gingerol, and [6]-shogaol reduced inflammation by 20, 25 and 38%. respectively when administered individually at a dose of 150 mg/kg. [6]-Shogaol efficacy was at the level of aspirin, used as a positive control. Grains of paradise extract has demonstrated an anti-inflammatory activity, which is in part due to the inhibition of COX-2 enzyme activity and expression of pro-inflammatory genes.

Toxicological evaluation of grains of paradise (Aframomum melegueta) [Roscoe] K. Schum.

ETHNOPHARMACOLOGICAL RELEVANCE: Grains of Paradise (Aframomum melegueta [Roscoe] K. Schum.) seeds are used in West Africa as a remedy for variety of ailments such as stomach ache, snakebite, diarrhea and they have reported anti-inflammatory properties. Additionally, the seeds contain gingerols and related compounds that may be useful against cardiovascular disease, diabetes, and inflammation. AIM OF STUDY: A 28-day sub-chronic toxicity study in male and female Sprague-Dawley rats was conducted to evaluate the safety of a Grains of Paradise extract. MATERIALS AND METHODS: An ethanolic extract of the seeds was evaluated for toxicological effect on rats. RESULTS: A dose-related increase in absolute and relative liver weights was observed in males and females dosed with 450 and 1500 mg/kg. There was a corresponding increase in alkaline phosphatase with no signs of steatosis or cirrhosis. At the same doses, there was a significant decrease in blood glucose in male rats. CONCLUSIONS: This study shows that Grains of Paradise extract may be useful as a treatment for diabetes, however liver toxicity should be considered.