Sources of natural phenolic antioxidants

Boskou Dimitrios

Abstract: An important field of research today is the control of ‘redox’ status with the properties of food and food components. Natural antioxidants present in the diet increase the resistance toward oxidative damages and they may have a substantial impact on human health. Dietary antioxidants such as ascorbates, tocopherols and carotenoids are well known and there is a surplus of publications related to their role in health. Plant phenols have not been completely studied because of the complexity of their chemical nature and the extended occurrence in plant materials. Extensively studied sources of natural antioxidants are fruits and vegetables, seeds, cereals, berries, wine, tea, onion bulbs, olive oil and aromatic plants. Attempts are also
made to identify and evaluate antioxidants in agricultural by-products, ethnic and traditional products, herbal teas, cold pressed seed oils, exudates resins, hydrolysis products, not evaluated fruits and edible leaves and other raw materials rich in antioxidant phenols that have nutritional importance and/or the potential for applications in the promotion of health and prevention against damages caused by radicals.

Read More …

Antioxidant activities, total phenolic and flavonoid contents of ethyl acetate extract of Mengkudu (Morinda citrifolia, L) fruit and its fractions

Abdul Rohman, Sugeng Riyanto dan Diah Utari

Abstract: This present study was carried out to evaluate antioxidant activities, total phenolic and total flavonoid contents of ethyl acetate extract of Mengkudu fruit and its fractions. Ethyl acetate extract was fractionated by column chromatography and yielded 15 fractions based on the identical TLC (thin layer chromatography) profile. Antioxidant activities in ethyl acetate extract and its fractions were determined by radical scavenging assay using DPPH (2,2-diphenyl-1-picrylhydrazyl) radical. The total phenolic and total flavonoid contents were determined spectrophotometrically. Among 15 fractions of ethyl acetate extract evaluated, fraction 8 (IC505,49 μg/mL) and fraction 7 (IC50 7,90 μg/mL) revealed antioxidant activities
that higher than that of vitamin E (IC50 8,27 μg/mL). The total phenolic contents ranged from 5.94 ± 0.08 to 36.52 ± 0.35 g of gallic acid equivalent/100 gram dry material whereas the total flavonoid contents ranged from 1.19 ± 0.02 to 17.65 ± 0.17 g of quercetin equivalent/100 gram dry material. A linier positive relationship existed between the antioxidant activities and total phenolic contents of the tested ethyl acetate extract and its fractions y = -1.220x + 44.022; r2 = 0.67, while the correlation between antioxidant activities and total flavonoid contents revealed a linier regression y = -2.202 x + 35.82; r2 = 0.4278.
Keywords: antioxidant activity, Morinda citrifolia, L, Fraction

Read More …

Pemanfaatan Maltodekstrin Dari Pati Singkong Sebagai Bahan Penyalut Lapis Tipis Tablet

Effionora Anwar

Abstract: The Use of Maltodextrin from Tapioca Starch as a Film Coating Tablet Material. Maltodexrin is a modifi ed starch product which can be use as a material fi lm coating tablet. The aim of the research was to study the capability of maltodextrin as a material fi lm coating exipient. Maltodextrin DE 5-10 was made by hidrolysis of tapioca starch with α-amylase enzyme from NOVO (Termamyl L120®), at 80° C, for 65 minute. Maltodextrin was used as a fi lm coating material at concentration 10%,15%,20% dan 25%. As a comparative fi lm coating material was used HPMC. The evaluation of the coating tablet was done accordance to Farmacope Indonesia third and fourth edition. The result show that maltodextrin DE 5-10 from tapioca starch can be used as fi lm coating at concentration 10-25% with concentration 10% gave better result a HPMC.
keywords: Maltodextrin, film coating

Read More …

Clinical Production, Stability Studies and PET Imaging With 16- α-fluoroestradiol (FES) in ER Positive Breast Cancer Patients

ABSTRACT Purpose: Fluoroestradiol FES has emerged as a valuable PET tracer to predict the response to hormone therapy in recurrent or metastatic breast cancer patients. A clinically acceptable product requires a rapid reliable synthesis and must be demonstrated to maintain chemical stability and receptor specific uptake during patient studies. FES then becomes a dependable tracer for the evaluation and management of breast cancer patients.
Methods: An improved automated radiosynthesis of FES was developed. Stability studies of the injectible form of FES were performed up to 24 h after dose formulation under normal storage conditions. A comparative FES/FDG PET imaging in ER+ breast cancer patients is reported.
Results: The improved synthesis procedure utilizes fewer hydrolysis steps and a single high performance liquid column chromatography (HPLC) purification of the labeled mixture affording FES in good yield with high radiochemical purity (>99%). Stability studies with purified FES in saline/ethanol (85:15 v/v) indicated no radiolytic or chemical degradation of this radiopharmaceutical when stored for 24 h at 20-24 °C. Positron Emission Tomography (PET) studies with FES and FDG in estrogen receptor positive (ER+) breast cancer patients indicated that while FDG accumulation was seen in all metabolically hyperactive sites, the uptake of
FES clearly delineated the ER+ tissues regions.
Conclusions: An improved automated synthesis of FES has been developed and the integrity of this product has been validated by long term stability studies and clinical PET imaging studies in ER+ breast cancer patients. A lack of concordance between FES and FDG uptake in a patient with metastatic breast cancer suggests specificity of the FES for tumors expressing estrogen receptors.

Read More …

Vinblastine – syntheses and preliminary imaging in cancer patients

ABSTRACT - Purpose: The primary aim of this work was to establish a radiolabeling procedure of vinblastine, a vinca alkaloid widely used in chemotherapy, with the positron-emitter carbon-11 for application in positron-emission-tomography (PET) studies in cancer patients. The optimized reaction conditions were transferred to an automated radiosynthesizer system for the preparation of vinblastine under GMP conditions for human use. We report about the whole body activity distribution after injection of vinblastine as well as the pharmacokinetic behavior in selected organs and the tumor in two patients that were investigated with vinblastine PET before chemotherapy. Methods: For carbon-11 labeling of vinblastine the reaction conditions were determined with respect to the two possible labeling precursors (i.e. methyl iodide and diazomethane), solvent, reaction temperature and reaction time. Both, diazomethane and methyl iodide were tested as labeling
precursors with the corresponding demethyl compound of vinblastine, i.e. the vinblastine acid and the potassium salt of vinblastine acid. Two patients with renal carcinoma underwent vinblastine PET before chemotherapy. One patient underwent a second scan during infusion of unlabeled vinblastine at a therapeutic dose.
Results: Best results for the labeling procedure were found when methylation was carried out at 100 °C within 20 min using 2 mg/mL of the potassium salt of vinblastine acid in DMSO and methyl iodide as labeling precursor. Based on methyl iodide starting activity a radiochemical yield of up 53 % vinblastine was achieved. In addition, the synthesis was transferred to a remotely controlled module for routine GMP conform production for human use. In large scale production runs up to 1 GBq of vinblastine was obtained ready for injection within 45 min after EOB. In one patient, whole body PET scans 40 min after injection of 112 MBq vinblastine showed a focally increased vinblastine uptake and vinblastine metabolite uptake, respectively in the known metastases, along with a slow but continuous washout during the measurement interval (0-60 min p.i.). Another patient showed no focally increased vinblastine uptake and vinblastine metabolite uptake in the tumor, where radioactivity concentration was comparable to that in the blood. In this patient, a second PET scan during infusion of unlabeled vinblastine revealed similar kinetics with a trend towards delayed hepatic metabolism and higher blood and tumor concentrations. Whereas this patient showed a partial response to chemotherapy, the first patient did not, hypothetically due to the observed vinblastine washout from the tumor. Conclusions: The carbon-11 labeling of vinblastine using methyl iodide is superior to the method using diazomethane. A well working automated radiosynthesis was established for the production of vinblastine for PET-investigations in cancer patients. The individual pharmacokinetic behavior of the chemo-therapeutic agent to the tumor can be assessed with PET, thus, can be considered to be a realistic approach for individualized chemotherapy.

Read More …

Cephalexin inhibits N-formylated peptide transport and intestinal hyperpermeability in Caco2 cells

ABSTRACT- Purpose. Intestinal barrier integrity is diminished in critical illness and inflammatory bowel disease. Bacterial-derived N-formylated peptides, absorbed by the intestinal oligopeptide transporter, hPEPT1, are involved in the pathogenesis of disease-induced intestinal barrier dysfunction, via stimulation of polymorphonuclear leukocyte (PMN) migration. The purpose of this study was to determine if the hPEPT1 substrate, cephalexin, inhibits the absorption of the Nformylated peptide, N-formyl-L-methionyl-Lleucyl-L-phenylalanine (“fMLP”), thereby preventing hyperpermeability in Caco2 cells. Methods. Caco2 monolayers were grown on permeable supports. fMLP (0.1 μM) was added to apical chambers with and without cephalexin (5 and 10 mM), and fMLP effective permeability was calculated. To determine the ability of cephalexin to attenuate intestinal dysfunction, Caco2 cells were co-cultured with human PMN’s in the presence of fMLP, cephalexin, and inflammatory cytokines. Monolayer integrity was assessed by measuring mannitol permeability. Results. Cephalexin 10 mM significantly reduced fMLP permeability (p=0.007).
Monolayer integrity (as indicated mannitol permeability) was decreased in cultures treated with inflammatory cytokines and fMLP, an effect that was attenuated by cephalexin (p<0.01). Conclusion. Cephalexin inhibits fMLP transport across cultured intestinal monolayers, and partially attenuates PMN-induced intestinal hyperpermeability. The use of pharmacologic hPEPT1 substrates may represent a novel means of preserving intestinal barrier integrity.

Read More …