Antitumor Effects of an Anthocyanin-Rich Grain Diet in a Mouse Model of Lewis Lung Carcinoma.

Functional foods enriched with plant polyphenol anthocyanins attract particular attention due to their health-promoting properties, including antitumor activity. We evaluated the effects of a grain diet rich in anthocyanins in a mouse model of Lewis lung carcinoma. Mice of the C57BL/6 strain were fed with wheat of near-isogenic lines differing in the anthocyanin content for four months prior to tumor transplantation. Although a significant decrease in the size of the tumor and the number of metastases in the lungs was revealed in the groups with both types of grain diet, the highest percentage of animals without metastases and with attenuated cell proliferation in the primary tumor were observed in the mice with the anthocyanin-rich diet. Both grain diets reduced the body weight gain and spleen weight index. The antitumor effects of the grain diets were associated with the activation of different mechanisms: immune response of the allergic type with augmented interleukin(IL)-9 and eotaxin serum levels in mice fed with control grain vs. inhibition of the IL-6/LIF system accompanied by a decrease in the tumor-associated M2 macrophage marker arginase 1 gene mRNA levels and enhanced autophagy in the tumor evaluated by the mRNA levels of Beclin 1 gene. Thus, anthocyanin-rich wheat is suggested as a promising source of functional nutrition with confirmed in vivo antitumor activity.

Use of over-the-counter mouthwashes as an additional measure in individual oral prophylaxis on adults with plaque-induced gingivitis: a double-blind, parallel, randomized controlled trial.

BACKGROUND: Plaque-induced gingivitis is a chronic inflammatory condition characterized by complete reversibility of tissue damage once the periodontal biofilm has been disorganised. The aim of this study was to evaluate the efficacy of two commercially available mouthwashes (MWs) versus a chlorhexidine (CHX) 0.12% MW in reducing gingival bleeding (GB) in adults with plaque-induced gingivitis. METHODS: The present study was a double-blind, parallel, randomized controlled trial involving 6492 gingival sites (i.e. 39 subjects × 28 teeth × 6 sites/tooth) aged 18-75 years. During a 2-week period, subjects were randomized to receive MWs: a control CHX 0.12% MW (group C, 1818 sites); a MW test containing CHX 0.09% + Citrox®/P complex (group CX, 2628 sites); a MW test based on natural compounds (group P, 2016 sites). GB was assessed at the inclusion visit (T0) and after 2 weeks of MW use (T1). Analyses of GB were compared between groups and then restricted to subjects with bleeding sites between 10 and 30% (moderate gingivitis) or ≥ 30% (severe gingivitis) at T0. Pairwise comparisons were made between groups and logistic regression was used to identify correlates of GB (T1). RESULTS: For total bleeding site analysis, GB reduction between T0 and T1 ranged from 23% (C), 26% (CX) and 36% (P), respectively (all p < 0.05). Multiple comparison between groups showed that group C was significantly less effective (p < 0.05) than groups CX and P. Splitting the analysis, in patients with severe gingivitis (≥ 30% bleeding sites at T0), all MWs had a positive effect on GB with a reduction at T1 of 36% (C), 33% (CX) and 42% (P), respectively. While GB reduction between T0 and T1, was significant for all groups, the comparison among groups showed no significant difference between group C and CX, whereas the improvement was significant for group P. On the other hand, in adults with moderate gingivitis (< 30% bleeding sites at T0), only CX and P had a positive effect on GB reduction at T1(9% in CX and 2% in P, respectively), although the differences between the three groups were not significant. CONCLUSION: The daily use of MWs with natural components (groups P and CX) for 2 weeks should be considered positively as an adjunct to individual oral prophylaxis to reduce GB compared to the control MW containing CHX 0.12% (group C) in healthy adults with plaque-induced gingivitis. For subjects with severe gingivitis, it is advisable to first use natural MW (P) and then MW based on CHX 0.09% with natural components (CX), compared to MW with CHX 0.12% (C). For adults with moderate gingivitis, P and CX can be advisable, even if no definitive recommendations can be drawn. TRIAL REGISTRATION: ACTRN12622000215729, 07/02/2022.

Recent developments in citrus bioflavonoid encapsulation to reinforce controlled antioxidant delivery and generate therapeutic uses: Review.

Citrus fruits contain numerous antioxidative biomolecules including phenolic acids, flavonols, flavanones, polymethoxyflavones (PMFs), and their derivatives. Previous in vitro and in vivo studies thoroughly investigated the antioxidant and therapeutic potential of bioflavonoids extracted from different citrus varieties and fruit fractions. Major bioflavonoids such as hesperidin, naringin, naringenin, and PMFs, had restricted their incorporation into food and health products due to their poor solubility, chemical stability and bioavailability. Considering these limitations, modern encapsulation methodologies such as hydrogelation, liposomal interactions, emulsifications, and nanoparticles have been designed to shield bioflavonoids with improved target distribution for therapeutic enhancements. The size, durability, and binding efficiency of bioflavonoid-loaded encapsulates were acquired by the optimized chemical and instrumental parameters such as solubility, gelation, dispersion, extrusion, and drying. Bioflavonoid-enriched encapsulates have been also proven to be effective against cancer, inflammation, neurodegeneration, and various other illnesses. However, in the future, newer natural binding agents with higher binding capacity might accelerate the encapsulating potential, controlled release, and enhanced bioavailability of citrus bioflavonoids. Overall, these modern encapsulation systems are currently leading to a new era of diet-based medicine, as demand for citrus fruit-based nutritional supplements and edibles grows.

Fast and Sensitive Determination of Bioflavonoids Using a New Analytical System Based on Label-Free Silver Triangular Nanoplates.

Optical sensors based on silver triangular nanoplates (AgTNPs) are insufficiently studied as probes for the spectrophotometric determination of biologically active compounds. In the present article, an interaction between label-free AgTNPs and bioflavonoids in the presence of silver(I) ions was assessed to outline the possibilities of AgTNPs as a colorimetric probe for the fast and sensitive determination of bioflavonoids. It is shown that the interaction was accompanied by a bathochromic shift of the local surface plasmon resonance band of nanoparticles and an increase in its intensity. Seven bioflavonoids differing in their structure were tested. The influence of the structure of analytes and the main external factors on the analytical signal is discussed in detail. It was found that the detection limits of bioflavonoids in the selected optimal conditions increased in the series morin < rutin = quercetin < taxifolin and came to 0.9, 1.2, 1.2, and 2.0 µmol L-1, respectively. Chrysin, naringenin, and naringin were found not to affect the spectral characteristics of AgTNPs. The suggested approach was applied for the spectrophotometric determination of flavonoids in pharmaceuticals and onion peel.

BIOFLAVONOIDS AS AGENTS FOR CORRECTING NITRO-OXIDATIVE STRESS AND SALIVARY GLAND FUNCTIONS IN RATS EXPOSED TO ALCOHOL DURING MODELED LIPOPOLYSACCHARIDE-INDUCED SYSTEMIC INFLAMMATORY RESPONSE.

OBJECTIVE: The aim: To investigate the effects of bioflavonoids (curcumin, epigallocatechin-3-gallate and quercetin) on nitro-oxidative stress and the functions of submandibular SGs in rats under alcohol exposure during SIR. PATIENTS AND METHODS: Materials and methods: The studies were conducted on 35 rats of the Wistar line weighing 205-220 g, divided into 5 groups of seven animals in each: the 1st group, control group I, included animals receiving isotonic sodium chloride solution intragastrically twice a day; the 2nd group, control group II, included rats exposed to alcohol (in a dose of 24 mg/kg intragastrically through gavage a twice a day) for last 2 weeks during lipopolysaccharide (LPS)-induced SIR; the rats of the 3rd, 4th and 5th groups exposed to alcohol during LPS-induced SIR, which also received bioflavonoids. The bioflavonoids ("Sigma-Aldrich, Inc.", USA) were as following: curcumin (in a daily dose of 200 mg/kg), epigallocatechin-3-gallate (in a daily dose of 40 mg/kg), and quercetin (in a daily dose of 200 mg/kg), respectively. SIR was induced by intraperitoneal administration of Salmonella typhi LPS (during the first week a dose of 0.4 µg/kg of body weight was administered 3 times a week; during the next 7 weeks of the experiment rats received 0.4 µg/kg of body weight once a week. The formation of superoxide anion radical (О2 -), activity of NO-synthase - total (NOS), its constitutive and inducible isoforms (cNOS, iNOS), and concentration of peroxynitrites and S-nitrosothiols were evaluated spectrophotometrically. To assess the functional status of submandibular SGs in their homogenate we determined α-amylase activity (spectrophotometrically) and the aquaporin-5 concentration (by enzyme-linked immunosorbent assay). through gav-age with orogastric cannul. RESULTS: Results: When applying bioflavonoids under the conditions of alcohol administration during SIR, NADH-induced .О2 - production decreased and yielded to the result in the control group II by 36.8% under administering curcumin, by 34.5% under administering epigallocatechin-3-gallate, and by 41.3% under administering quercetin. The total NOS activity in SGs tissues was inferior by 42.8% to the relevant data in the control group II (under curcumin administration), by 33.7% (under epigallocatechin-3-gallate administration) and by 46.6% (under quercetin administration); and the iNOS activity decreased by 47.0, 38.3 and 52.0%, respectively. Under the administration of bioflavonoids peroxynitrites concentration in the submandibular SGs tissues was inferior to the control group II by 35.6% (under curcumin administration), by 37.4% (under epigallocatechin-3-gallate administration), and by 39.3% (under quercetin administration); the content of S-nitrosothiols was lower by 34.5, 31.1 and 35.3%, respectively. The administration of bioflavonoids led to the changes in α-amylase activity in the submandibular SGs tissues: its values exceeded the relevant data in the control group II by 40.4% (under curcumin administration), by 38.2% (under epigallocatechin-3-gallate administration), and by 34.1% (under quercetin administration); under those conditions aquaporin-5 concentration grew in 2.66, 2.61 and 2.55 times, respectively. CONCLUSION: Conclusions: The use of bioflavonoids (curcumin, epigallocatechin-3-gallate, and quercetin) under the combined administration of 40% ethanol solution and LPS considerably limits the development of nitro-oxidative stress in the tissues of the submandibular SGs. The administration of the bioflavonoids increases the level of cNOS coupling, and improves the functional status of the submandibular SGs under the combined administration of alcohol and LPS enhancing the activity of α-amylase and concentration of aquaporin-5.

[Assessment of antimicrobial activity of bioflavonoid CITROX and chlorhexidine combination against P. gingivalis (in vitro)]. / Otsenka antisepticheskikh svoistv kombinatsii khlorgeksidina i bioflavonoida CITROX v otnoshenii P. gingivalis (in vitro).

OBJECTIVE: The aim of the study - evaluation of the antiseptic properties of the combination of chlorhexidine and bioflavonoid CITROX against P. gingivalis. MATERIAL AND METHODS: Clinical isolates of microbial cultures from the collection of the Department of Microbiology, Immunology, Virology of the Moscow State Medical University named after A.I. Evdokimov: P. gingivalis. Primary seeding of the studied material was carried out on nutrient media produced by Himedia Laboratories Pvt. Limited (India): Colombian agar with the addition of 5% defibrinated blood and a selective additive for the isolation of non-spore anaerobes. To conduct the experiment, a thermostatic rotary system - RTS-1 (Biosan, Latvia) was used, which performs a modern type of mixing due to the formation of a vortex-type diffusing effect. The interpretation of the results was carried out by changing the optical density index (the indicator in McFarland units) at a wavelength of λ = 850 nm. RESULTS: The combination of CITROX + chlorhexidine 0.05% more effectively suppresses the growth of periodotopathogenic bacteria than chlorhexidine 0.05%, prolonging the adaptive phase (lag phase) of the growth of P.gingivalis bacteria and can be considered as an alternative to chlorhexidine without additives. Prolongation of the lag phase increases the time until the first clinical symptoms appear, as a result, the body has more time to form an immune response. CONCLUSION: The combination of the complex of bioflavonoids CITROX and chlorhexidine bigluconate in concentrations of 0.05% and 0.2% is active against P. gingivalis and can be considered as an alternative to chlorhexidine without additives. The inclusion of CITROX in the rinse aid reduces the concentration of chlorhexidine in the rinse aid, which can lead to a decrease in the severity of undesirable effects and be considered as an alternative remedy in the treatment of periodontal diseases.

Amalgamation of in-silico, in-vitro and in-vivo approach to establish glabridin as a potential CYP2E1 inhibitor.

CYP2E1 is directly or indirectly involved in the metabolism of ethanol and endogenous fatty acids but it plays a major role in the bio-activation of toxic substances that produce reactive metabolites leading to hepatotoxicity. Therefore, identification of CYP2E1 inhibitor from bioflavonoids class having useful pharmacological properties has dual benefit regarding avoidance of severe food-drug/nutraceutical-drug interaction and scope to develop a phytotherapeutics through an intended pharmacokinetic interaction.In the present study, we aimed to identify CYP2E1 inhibitor from experimental bioflavonoids which are unexplored for CYP2E1 inhibition till date using in-silico, in-vitro and in-vivo approaches.Results of in-vitro CYP2E1 inhibitory studies using CYP2E1-mediated chlorzoxazone 6-hydroxylation in human liver microsomes showed that glabridin have the highest potential than fisetin, epicatechin, nobiletin, and chrysin to inhibit CYP2E1 enzyme. Mechanistic investigations indicate that glabridin is a competitive CYP2E1 inhibitor. Molecular docking study results demonstrate that glabridin strongly interacted with the active site of human CYP2E1 enzyme. Pharmacokinetics of a CYP2E1 substrate in mice model indicates a significant alteration of chlorzoxazone and 6-hydroxychlorzoxazone plasma levels in the presence of glabridin. Further studies are needed to confirm the results at clinical level.Overall, glabridin is found to be a potential CYP2E1 inhibitor.

Evaluation of in vitro biological activities: antioxidant; anti-inflammatory; anti-cholinesterase; anti- xanthine oxidase, anti-superoxyde dismutase, anti-α-glucosidase and cytotoxic of 19 bioflavonoids.

Pure compounds belonging to phenolic family were studied for their biological potential such as 5,8-dihydroxy-1,4-naphthoquinone (M1), rutin hydrate (M2), 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (M3), taxifolin (M4), myricetin (M5), plumbagin (M6), silibinin (M7), dihydromyricetin (M8), shikonin (M9), quercetin 3-ß-D-glucoside (M10), (±)-taxifolin hydrate (M11), cardamonin (M12),(-)-epicatechin (M13), 9-chloro-10-hydroxy-anthracene-1,4-dione (M14), 9-chloro-10-hydroxy-2,3-dimethyl-anthracene-1,4-dione (M15), 2-chloro-3-(2-hydroxy-5-methylanilino)-1,4-naphthoquinone (M16), 2-chloro-3-(4-hydroxy-phenylamino)-(1,4) naphthoquinone (M17), 2-chloro-3-(3,5-di-tert-butyl-4-hydroxy-phenyl)-(1,4)-naphtoquinone (M18), and myricitrin dihydrate (M19). These molecules were chosen based on two reasons; the limited or total absence of their exploitation in several studied activities and the use of other tests for the same activity. The evaluation of the in vitro anti-acetyl-cholinesterase (AChE), anti-5-lipoxygenase (5-LOX), anti-xanthine oxidase (XOD), anti-alpha glucosidase, anti-superoxide dismutase (SOD), anti-oxidant (DPPH (1, 1-diphenyl-2-picrylhydrazyl) and ABTS (2, 2- azinobis-3-ethylbenzothiazoline-6-sulphonate)), and anticancer activities of mentioned 19 molecules was explored during this work. M3, M14, M15, M16, M17, M18, M19 were exploited for the first time for such purposes. Tested compounds were shown to have interesting radical scavenging abilities against DPPH radicals, and the highest molecules among them were M19 and M5 (IC50 = 12.0 and 15.5 µM, respectively), and M4, M19 and M2 against ABTS (IC50= 1.9, 4.3 and 4.3 µM, respectively). Moreover, the majority of products showed very important cytotoxic activity since IC50 values were ranging between (IC50= 0.2 µM (M1) and 79 µM (M8)) against HCT116 cell line, and values of IC50= 0.2 µM for M1 against MCF7 cell line. All new molecules (non studied before) were shown to have great cytotoxic effect against both cancer cell lines.Furthermore, molecule M5 was shown to have anti-inflammatory potential via the inhibition of 5-LOX enzyme (65% at 100 µM). In addition, M19 showed important anti XOD activity with 47% of inhibition at 100 µM. Also, it has been found that compound M3 had the best anti alpha glucosidase activity with 43.8 % of inhibition at 100 µM, the highest anti-AChE effect (IC50= 14.5 µM), and the best effect towards SOD (IC50= 10.0 µM).  A structure-activity relationship study was also performed.

Optimized microwave-assisted extraction of bioflavonoids from Albizia myriophylla bark using response surface methodology.

Bioflavonoids are of great interest due to their health-benefitting properties and possible protection against certain types of diseases. A microwave-assisted extraction (MAE) method was investigated for maximum retention of total bioflavonoids from Albizia myriophylla bark (AMB). Response surface methodology (RSM) using central composite design were employed for obtaining the best possible combination of MAE process parameters including microwave power (400-900 W), liquid/solid ratio (20-40 ml/g), extraction time (20-40 min) and ethanol concentration (60-100%). Optimum conditions of extraction under which predicted maximum bioflavonoids yield of 152.74 mg QE/g DW and antioxidant activity of 75.33% in close proximity with the experimental values were: microwave power 728 W, liquid/solid ratio 24.70 ml/g, extraction time 39.86 min and ethanol concentration 70.36%. Satisfactory statistical parameters (R2), ANOVA for the model and lack-of-fit testing provided an adequate mathematical description of the MAE of bioflavonoids with high antioxidant activity. Therefore, MAE of AMB using RSM could be termed as a time-saving and an efficient method resulting to high yield with increased antioxidant activity. Also, HPLC analysis of AMB revealed the presence of bioflavonoids viz., naringin, quercetin and apigenin; which may be further extensively studied for use as therapeutics against various health issues.

Agathisflavone: Botanical sources, therapeutic promises, and molecular docking study.

In this article, we have summarized the biological sources and pharmacological activities of agathisflavone along with molecular docking studies to correlate the interaction of this biflavonoid and biomacromolecules involving in its biological effects observed in database-oriented scientific reports. For this, an up-to-date (from 1991 to October 2018) search was done on the databases such as PubMed, Science Direct, Web of Science, Scopus, The American Chemical Society, Clinicaltrials.gov, and Google Scholar databases. The findings suggest that agathisflavone possesses antioxidant, anti-inflammatory, antiviral, antiparasitic, cytotoxic, neuroprotective, and hepatoprotective activities. An in silico study of agathisflavone against 17 essential proteins/enzymes revealed that inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 are the most efficient enzymes for the interaction and binding of this biflavonoid for its anti-inflammatory activity. In conclusion, agathisflavone may be one of the promising plant-derived lead compounds in the treatment of oxidative stress, inflammatory diseases, microbial infection, hepatic and neurological diseases and disorders, and cancer. © 2019 IUBMB Life, 71(9):1192-1200, 2019.

[The expression of apoptosis and autophagy markers in transplantable rat kidney cancer with the administration of flavonoid-containing hedge hyssop ( L.) extract]. / Ékspressiia markerov apoptoza i autofagii v perevitom rake pochki u krys pri vvedenii flavonoidsoderzhashchego ékstrakta avrana lekarstvennogo (L.).

OBJECTIVE: To establish the mechanisms of pathomorphism of transplantable kidney cancer in rats that used flavonoid-containing hedge hyssop (Gratiola officinalis L.) extract in an in vivo experiments. MATERIAL AND METHODS: The experiment was carried out on 30 male Wistar rats with transplantable kidney cancer PA. At 72 hours after tumor inoculation, the rats in the experimental groups received hedge hyssop extract at an oral or intramuscular dose of 110 mg/kg/day for 12 days. A comparison group consisted of the animals with a tumor, but without exposure. The investigators used the immunohistochemical markers of apoptosis (p53, bax, bcl-2, Fas-receptor, Fas-ligand), autophagy (LC3B), proliferation (Ki-67), and angiogenesis (VEGF). During statistical data processing, the Shapiro-Wilk test was used to test the normality of the indicator distribution in the groups. Cramer-Welch's t-test was also employed to compare the groups. RESULTS: Histological examination of tumor tissue under the action of hedge hyssop extract showed the emergence of extensive areas of damage (necrosis and apoptotic bodies). With both routes of hedge hyssop extract administration, there was a sharp decrease in the expression of the proliferation markers Ki-67 and the angiogenesis marker VEGF and a high expression of the apoptosis markers p53, bax, CD95 (Fas/APO-1), and FAS-ligand in tumor cells and its absence in the comparison group. All the described changes were more pronounced with intramuscular administration. The expression of the autophagy marker LC3B increased with the oral administration of hedge hyssop extract and decreased with its intramuscular administration. CONCLUSION: A pronounced pathomorphism of kidney cancer develops due to consumption of hedge hyssop extract. This suppresses the proliferation, angiogenesis, and activation of apoptotic signaling and mitochondrial pathways and blocks protective autophagy. The autophagy marker LC3B can be used as an additional criterion for evaluating the therapeutic pathomorphism of tumors.

[Pharmacology of the drugs prescribed for chronic venous diseases]. / Farmakologiia preparatov, primeniaiushchikhsia pri khronicheskikh zabolevaniiakh ven.

The main groups of the drugs used for pharmacotherapy of chronic venous disease are considered. The main therapeutic targets of the drugs including their effect on venous wall tone, permeability and inflammation are described.

Citrus bioflavonoids dipeptidyl peptidase-4 inhibition compared with gliptin antidiabetic medications.

This study compared dipeptidyl peptidase-4 (DPP-4) inhibitory activity of citrus bioflavonoid nutraceuticals compared with three gliptins. Citrus bioflavonoid standards and three commercially available citrus bioflavonoid supplements (Thompson's Super Bioflavonoid Complex®(SB), Ethical Nutrients Bioflavonoids Plus Vitamin C®(EN), and Country Life Citrus Bioflavonoids and Rutin®(CB)) were considered in this study. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis was undertaken to identify and quantitate the citrus bioflavonoids present in each supplement. The DPP-4 inhibitory activity was determined by fluorometric assay. All of the tested individual citrus flavonoids demonstrated DPP-4 inhibitory activity, with IC50 values ranging from 485 µM (rutin) to 5700 µM (hesperitin and eriodictyol). Similarly, the flavonoid supplements had IC50 values of 16.9 mg/mL (EN), 3.44 mg/mL (SB) and 2.72 mg/mL (CB). These values compare with gliptin IC50 values of 0.684 µM (sitagliptin), 0.707 µM (saxagliptin) and 2.286 µM (vildagliptin). The supplement flavonoid content varied from 11.98% (CB) to 5.26% (EN) and 14.51% (SB) of tablet mass, corresponding to daily flavonoid doses of around 300, 150 and 400 mg, respectively, with CB and SB containing rutin at levels of 7.0% and 7.5% of tablet mass, respectively. While our data demonstrated that citrus bioflavonoid based supplements do possess DPP-4 inhibitory activity, they are several orders of magnitude less potent than gliptins. Further studies using higher concentrations of citrus bioflavonoids, as well as investigations into antioxidant properties which may add additional benefit are warranted.

Investigation into the Emerging Role of the Basic Amino Acid L-Lysine in Enhancing Solubility and Permeability of BCS Class II and BCS Class IV Drugs.

BACKGROUND: The search for a simple and scalable approach that can improve the two key biopharmaceutical processes (solubility and permeability) for BCS Class II and BCS Class IV has still been unmet need. PURPOSE: In this study, L-lysine was investigated as a potential excipient to tackle problems with solubility and permeability. Bendazac (Class II); quercetin and rutin (Class IV) were employed. METHODS: Drugs-lysine complexes in 1:1 M ratios were prepared by co-precipitation and co-grinding; characterized for solubility, partition coefficient, DSC, FTIR, SEM, dissolution rate and permeability. Chemical stability of quercetin-lysine and rutin-lysine was studied by assessing antioxidant capacity using Trolox and CUPRAC assays. RESULTS AND CONCLUSION: Drugs-lysine salt/complexes were confirmed. Solubility enhancement factors ranged from 68- to 433-fold increases and dissolution rates were also significantly enhanced by up to 6-times, compared with drugs alone. With the exception of rutin-lysine, Papp for bendazac-lysine and quercetin-lysine enhanced by 2.3- to 4-fold. Papp for quercetin (Class IV) benefited more than bendazac (Class II) when complexed with lysine. This study warrants the use of L-lysine as a promising excipient for enhanced solubility and permeability of Class II and Class IV, providing that the solubility of the drug is ensured at 'the door step' of absorption sites.

Assessment of the Effect of Dietary Modifications and Bioenteric Intragastric Balloon Treatment on the Changes of Some Morphological and Biochemical Parameters in Obese Patients.

Obesity is the most common disease of affluence of the XXI century. According to WHO (World Health Organization), it is defined as a chronic metabolic disorder manifested by excessive accumulation of adipose tissue with high tendency for familial occurrence. According to WHO, obesity reaches epidemic proportions in many countries. High BMI (Body Mass Index) correlates with coexisting diseases. Traditional dietetic treatment often does not bring any results. A form of conservative (non-surgical) support for patients in fighting with obesity is the reduction of stomach volume by bioenteric intragastric balloon (BIB) treatment. The aim of the work was to develop a diet with anti-inflammatory properties, well-tolerated by the patients after BIB treatment. An American diet was modified by changing the composition of fatty acids, increasing anti-oxidative potential and adding synbiotics for patients treated with BIB. Chemical analysis of reconstructed food ratios of recommended diet was performed, analysing the content of micronutrients, composition of fatty acids, antioxidative capacity, reducing power and the content of polyphenols. Improvement in anthropometric measurement results and satisfying body weight loss were obtained, while preserving fat-free body mass. Improvement in the parameters of lipid metabolism was also observed, that is, decrease in total CH (cholesterol) and TG (triglycerides), and normalized concentration of HDL (high density lipoproteins) and LDL (low density lipoproteins) fractions. Reduced concentration of glucose in blood and lower blood pressure was also noted. Performed study confirms the effectiveness of complex treatment with BIB and properly adjusted individualized diet. Observations and own experience allow to deduce that patients who resign from systematic contact with a dietician cannot maintain reduced body weight. Abandoning previous habits is the only way to maintain the effect of weight loss. Most importantly, the change in patients' awareness and consequent behaviour in the future are crucial. Even though genes may contribute to obesity, environmental factors mainly determine the possibility of the disease to occur. Therefore, the change of patients' lifestyle after body weight reduction will decide on their fate.

Statistical optimization of an RP-HPLC method for the determination of selected flavonoids in berry juices and evaluation of their antioxidant activities.

An isocratic RP-HPLC method for the separation and identification of selected flavonoids (quercetin, rutin, luteolin-7-O-glucoside, kaempferol and kaempferol-3-O-glucoside) in commercial berry juices (blackcurrant, blueberry, red raspberry and cherry) was developed with the aid of central composite design and response surface methodology. The optimal separation conditions were a mobile phase of 85:15 (% v/v) water-acetonitrile, pH 2.8 (adjusted with formic acid), flow rate 0.5 mL min-1 and column temperature 35°C. The obtained levels of bioflavonoids (mg per 100 mL of juice) were as follows: for quercetin, ca. 0.21-5.12; for kaempferol, ca. 0.05-1.2; for rutin, ca. 0.4-6.5; for luteolin-7-O-glucoside, ca. 5.6-10.2; and for kaempferol-3-O-glucoside, ca. 0.02-0.12. These are considerably lower than the values in fresh fruits. Total phenolic, flavonoid and anthocyanin contents were determined spectrophotometrically. Total flavonoid content varied as follows: blackcurrant > blueberry > red raspberry > cherry. The antioxidant activity of juice extracts (DPPH and ABTS methods) expressed as IC50 values varied from 8.56 to 14.05 mg L-1 . These values are ~2.5-3 times lower than quercetin, ascorbic acid and Trolox®, but compared with rutin and butylhydroxytoluene, berries show similar or better antioxidant activity by both the DPPH and ABTS methods.

A Phase I Dose Escalation Study Demonstrates Quercetin Safety and Explores Potential for Bioflavonoid Antivirals in Patients with Chronic Hepatitis C.

The hepatitis C virus (HCV) infects more than 180 million people worldwide, with long-term consequences including liver failure and hepatocellular carcinoma. Quercetin bioflavonoids can decrease HCV production in tissue culture, in part through inhibition of heat shock proteins. If quercetin demonstrates safety and antiviral activity in patients, then it could be developed into an inexpensive HCV treatment for third world countries or other affected populations that lack financial means to cover the cost of mainstream antivirals. A phase 1 dose escalation study was performed to evaluate the safety of quercetin in 30 untreated patients with chronic HCV infection and to preliminarily characterize quercetin's potential in suppressing viral load and/or liver injury. Quercetin displayed safety in all trial participants. Additionally, 8 patients showed a "clinically meaningful" 0.41-log viral load decrease. There was a positive correlation (r = 0.41, p = 0.03) indicating a tendency for HCV decrease in patients with a lower ratio of plasma quercetin relative to dose. No significant changes in aspartate transaminase and alanine transaminase were detected. In conclusion, quercetin exhibited safety (up to 5 g daily) and there was a potential for antiviral activity in some hepatitis C patients.

Rapid extraction and analysis method for the simultaneous determination of 21 bioflavonoids in Siegesbeckia pubescens Makino.

A novel and rapid microwave extraction and ultra high performance liquid chromatography coupled with a triple quadrupole-linear ion trap mass spectrometry method was developed and validated for the determination of 21 bioflavonoids in Siegesbeckia pubescens Makino. The optimal conditions for the extraction of flavonoids from Siegesbeckia pubescens Makino involved the use of methanol as the extraction solvent, a microwave temperature of 70°C, an extraction time of 11 min, and a solvent-to-solid ratio of 40 mL/g. Chromatographic separation was achieved on a Waters ACQUITY UPLC BEH C18 column(100 × 2.1 mm, 1.7 µm) with a gradient mobile phase (A: 0.3% v/v aqueous formic acid and B: acetonitrile) at a flow rate of 0.25 mL/min. All calibration curves showed good linearity (r > 0.999) within the test ranges. The method developed was validated with acceptable sensitivity, intra- and interday precision, reproducibility, and extraction recoveries. The validated method was successfully applied to determine the contents of 21 bioflavonoids in Siegesbeckia pubescens Makino from different sources.

Phytochemicals as Anticancer and Chemopreventive Topoisomerase II Poisons.

Phytochemicals are a rich source of anticancer drugs and chemopreventive agents. Several of these chemicals appear to exert at least some of their effects through interactions with topoisomerase II, an essential enzyme that regulates DNA supercoiling and removes knots and tangles from the genome. Topoisomerase II-active phytochemicals function by stabilizing covalent protein-cleaved DNA complexes that are intermediates in the catalytic cycle of the enzyme. As a result, these compounds convert topoisomerase II to a cellular toxin that fragments the genome. Because of their mode of action, they are referred to as topoisomerase II poisons as opposed to catalytic inhibitors. The first sections of this article discuss DNA topology, the catalytic cycle of topoisomerase II, and the two mechanisms (interfacial vs. covalent) by which different classes of topoisomerase II poisons alter enzyme activity. Subsequent sections discuss the effects of several phytochemicals on the type II enzyme, including demethyl-epipodophyllotoxins (semisynthetic anticancer drugs) as well as flavones, flavonols, isoflavones, catechins, isothiocyanates, and curcumin (dietary chemopreventive agents). Finally, the leukemogenic potential of topoisomerase II-targeted phytochemicals is described.

A rapid extraction and analysis method for the simultaneous determination of 26 bioflavonoids in Portulaca oleracea L.

INTRODUCTION: Portulaca oleracea L. (P. oleracea, purslane) is an edible plant that is widely distributed around the world, and flavonoids are its main bioactive constituents. Therefore, the detection of flavonoids is very important for a better understanding of its pharmacological actions and to monitor the product quality control of P. oleracea. OBJECTIVE: To develop a rapid method to extract and determine 26 bioflavonoids in P. oleracea, based on microwave extraction (MWE) and triple quadrupole-linear ion trap mass spectrometry. METHODS: The optimal conditions of MWE for the extraction of flavonoids from P. oleracea involved the use of methanol as the extraction solvent, a microwave power of 300 W, an extraction time of 450 s, and a solvent-to-solid ratio of 30 mL/g. The samples were analysed using an ultra-performance liquid chromatograph coupled with a triple quadrupole-linear ion trap mass spectrometer (UPLC-MS/MS) system. RESULTS: The calibration curves of all 26 analytes showed good linearity (r ≥ 0.999) and the intra- and interday precisions and repeatability were all within required limits. The mean recoveries measured at three concentrations were higher than 94.2%, with RSDs lower than 2.94% for the targets. CONCLUSION: The established MWE/UPLC-MS/MS method is a rapid and effective method for quality evaluation of P. oleracea from different production regions and different harvest periods.