ARTICLE | doi:10.20944/preprints202007.0553.v1
Subject: Keywords: bioavailability, heavy metals, BCR extraction, lagoon, sediments
Online: 23 July 2020 (11:47:24 CEST)
Heavy metals have been implicated as Lagoon pollutants from sources such as agriculture, mining and manufacturing industries and waste water treatment works. A study was carried out in the University of Lagos lagoon to investigate the seasonal bioavailability of the heavy metal contaminants Cd, Cr, Cu, Pb and Zn. The physical parameters pH, redox potential, temperature, TDS and conductivity were measured on site. Dried sediment samples were extracted using the Community Bureau of Reference (BCR) sequential procedure and analysed by ICP-OES. A certified reference material (CRM), BCR 701 (lake sediment) was used for quality assurance with recoveries ranging between 80-120%. Statistical analysis (ANOVA) showed that there was a significant difference between metal distribution in the dry and wet seasons. Cu, Pb and Zn were in the available fractions (carbonate, Fe/Mn oxide and organic). Cu was highest in the Fe/Mn oxide and organic fractions. This indicated that an increase in organic matter and reducing agents will avail the Cu. Zn was distributed in all fractions while Pb was found in the Fe/Mn oxide fraction (3.93- 21.3 %). Results showed that the bioavailability of Cu, Pb and Zn was high. Metal bioavailability by BCR indicates a potential risk of pollution in lagoon sediments as the available metals exceeded the permissible Sediment Quality Assessment Guidelines (SQAG’s) from Environmental Protection Agency (EPA).
ARTICLE | doi:10.20944/preprints201711.0109.v1
Online: 16 November 2017 (10:59:25 CET)
The objective of the research was to evaluate the concentration of organochlorine pesticides in sediment of the Alvarado Veracruz lagoon system, Mexico. To define the risk that causes to the public health the consumption of organisms that inhabit in sediments of this ecosystem. In 20 out of 41 stations analyzed, 11 prohibited organochlorine pesticides were identified, such as hexachlorocyclohexane, lindane, aldrin, dieldrin, endrin, among others. The highest concentrations were: aldrin 46.05; β-HCH 42.11; α-HCH 38.44; γ-HCH (lindane) 34.20; δ-HCH 31.61; methoxychlor 29.40; heptachlor epoxide 25.70; heptachlor 24.11; dieldrin 22.13; endrin 21.23; and endrin aldehyde 12.40 ng g-1. Concentrations reported are prohibited in international standards. In Mexico it is necessary to establish permissible limits in the environmental legislation for this matrix. There is a strong need to demonstrate, with scientific studies, the level of concentration reported by impact of compounds widely used in agricultural-livestock activities.
ARTICLE | doi:10.20944/preprints201810.0584.v1
Subject: Biology, Physiology Keywords: resveratrol; magnesium dihydroxide; solubility; bioavailability; dissolution rate; microparticles
Online: 25 October 2018 (03:53:04 CEST)
Resveratrol, because of its low solubility in water and its high membrane permeability, is collocated in the second class of the biopharmaceutical classification system, with limited bioavailability due to its dissolution rate. Solid dispersion of resveratrol supported on magnesium dihydroxide (RESV@MDH) was evaluated to improve solubility and increase bioavailability of resveratrol. Fluorimetric microscopy and granulometric analysis display three types of microparticles with similar size: type 1 that emitted preferably fluorescence at 463 nm (λecc 358 nm), type 2 that emitted preferably fluorescence at 605 nm (λecc 550 nm) andtype 3 that are non-fluorescent. Micronized pure resveratrol display only microparticles type 1 whereas type 3 are associated to pure magnesium dihydroxide. Dissolution test in simulated gastric environment resveratrol derived from RESV@MDH in comparison to resveratrol alone displayed better solubility. According to the biopharmaceutical classification, an increase of 3 fold of resveratrol bioavailabilitywas observed after oral administration of 50 mg/Kg of resveratrol of RESV@MDH in rabbits. We hypothesize that type 2 microparticles represent magnesium dihydroxide microparticles with a resveratrol shell and that they are responsible for the improved resveratrol solubility and bioavailability of RESV@MDH.
ARTICLE | doi:10.20944/preprints202103.0649.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: wheat; micronutrient; macronutrient; source-sink regulation; biofortification; phytate; bioavailability
Online: 25 March 2021 (17:17:10 CET)
In order to better understand the source-sink flow and relationships of Zinc (Zn) and other nutrients in wheat (Triticum aestivum L.) plants for biofortification and improving grain nutritional quality, effects of reducing photoassimilate source (through the flag leaf removal and spike shading) or sink (through 50% spikelets removal) in the field on accumulation of Zn and other nutrients in wheat grains of two cultivars (Jimai 22 and Jimai 44) were investigated under two soil Zn application levels. The single panicle weight (SPW), kernel number per spike (KNPS), thousand kernel weight (TKW), total grain weight (TGW), concentrations and yields of various nutrient elements (Zn, Fe, Mn, Cu, N, P, K, Ca and Mg), phytate phosphorus (phytate-P), phytic acid (PA) and phytohormones (ABA: abscisic acid, and the ethylene precursor ACC: 1-aminocylopropane-1-carboxylic acid), and C/N ratios were determined. Soil Zn application significantly increased concentrations of grain Zn, N and K. Cultivars showing higher grain yields had lower grain protein and micronutrient nutritional quality. SPW, KNPS, TKW (with an exception of TKW in half spikelets removal), TGW, and nutrient yields in wheat grains were most severely reduced by half spiklets removal, secondly by spike shading, and slightly by flag leaf removal. Grain concentrations of Zn, N and Mg consistently showed negative correlations with SPW, KNPS and TGW, but positively with TKW. There were general positive correlations among grain concentrations of Zn, Fe, Mn, Cu, N and Mg, and bioavailability of Zn and Fe (estimated by molar ratios of PA/Zn, PA × Ca/Zn, PA/Fe, or PA × Ca/Fe). Although concentrations of Zn and Fe were increased and Ca was decreased in treatments of half spikelets removal and spike shading, the simultaneously increased PA limited the increase in bioavailability of Zn and Fe. In general, different nutrient elements interact with each other and are affected to different degrees by source-sink manipulations. Elevated endogenous ABA levels and ABA/ACC ratios were associated with increased TKW and grain-filling of Zn, Mn, Ca and Mg, and inhibited K in wheat grains. However, effects of ACC were diametrically opposite. These results provide basis for wheat grain biofortification to alleviate human malnutrition.
REVIEW | doi:10.20944/preprints202004.0100.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: ellagic acid; oral administration; bioavailability; microformulations; nanoformulations; solubility enhancement
Online: 7 April 2020 (12:02:54 CEST)
Ellagic acid, a polyphenolic compound present in fruits and berries, has recently been object of extensive research for its antioxidant activity, which might be useful for the prevention and treatment of cancer, cardiovascular pathologies, and neurodegenerative disorders. Its protective role justifies numerous attempts to include it in functional food preparations and in dietary supplements not only to limit the unpleasant collateral effects of chemotherapy. However, ellagic acid use as chemopreventive agent has been debated because of its poor bioavailability associated to low solubility, limited permeability, first pass effect, and interindividual variability in gut microbial transformations. To overcome these drawbacks, various strategies for oral administration including solid dispersions, micro-nanoparticles, inclusion complexes, self-emulsifying systems, polymorphs have been proposed. Here, we have listed an updated description of pursued micro/nanotechnological approaches focusing on the fabrication processes and the features of the obtained products, as well as on the positive results yielded by in vitro and in vivo studies in comparison to the raw material. The micro/nano-sized formulations here described might be exploited for pharmaceutical delivery of this active, as well as for the production of nutritional supplements or for the enrichment of novel foods.
ARTICLE | doi:10.20944/preprints201712.0038.v1
Subject: Earth Sciences, Environmental Sciences Keywords: sewage sludge recycling; soil organic fertility; heavy metals bioavailability
Online: 7 December 2017 (05:41:57 CET)
The biomass fraction of processed municipal and industrial wastes added to soil can maintain, and in some case improve, the soil’s organic fertility. One of the main constraints in the agricultural use of the sewage sludge is its content of heavy metals. In the long term, soil administration of sewage sludge in agriculture could result in a risk of environmental impact. The aim of this research was to evaluate the effects of medium-term fertilization with sewage sludge diversely processed on the soil’s organic carbon content and humification – mineralization soil’s processes and on the physical and mechanical properties of soil. Furthermore, the heavy metals accumulation in soil, in their total and available form, has been investigated. After eight years of administration to soil, the use of sewage sludge as an agricultural soil amendment has contributed to maintaining the soil’s organic fertility. An increase in concentrations of total Ni and Zn was detected in soil. For bioavailable form (DTPA-extractable) this trend was evidenced for all heavy metals analysed. However, the concentrations of total and available heavy metals in the soil did not exceed the legal threshold established by Italian law for unpolluted soils.
ARTICLE | doi:10.20944/preprints201710.0109.v1
Subject: Earth Sciences, Environmental Sciences Keywords: dust; bioavailability; particle sizes; heavy metals; health risk; exposure
Online: 17 October 2017 (03:59:40 CEST)
In this study, we attempted to verify the hypothesis that total metals bound to dust of different particle sizes may reflect pollution levels, but cannot predict its bioavailability and risks in human health assessments. Dust samples were collected using active sampling method; during the dry season months of November, 2014 to March, 2015 at different locations in Akure (7˚10ʹN and 5˚15ʹE). The samples were sorted into different particle sizes (< 10µm, 10 – 50 µm, >50µm), analyzed for some physicochemical properties and assessed for metals bioavailability using two-step physiological extraction method. The amount of metals (Cd, Cu, Cr, Ni, Pb, Zn and Mn) released in each particle sizes were determined using Perkin-Elmer 6000 Inductively Coupled Plasma - Atomic Emission Spectrometry (ICP-AES) analysis. The results showed that bioavailability of some metals (Cd, Ni, Pb, and Zn) decreases with increasing particle sizes, however, the reverse trend was observed for Mn, Cu and Fe concentrations. This may be attributed to some combination of physicochemical characteristics of the dust and metal speciation. Hence, it was concluded that metal bioaccessibility in dust can best be described by the knowledge of physicochemical characteristics. The exposure dose of the metals showed that cancer risks due to inhalation were very high when compared to other exposure routes (ingestion and dermal contact). The calculated non-cancer (HQ) and cancer risk (HI) for humans in the area showed values higher than unity, indicating possibility of the metals’ body burden.
REVIEW | doi:10.20944/preprints202208.0021.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Solubility; Bioavailability; Dissolution; Poorly Soluble Drugs; Drug Solubility Enhancement Techniques
Online: 1 August 2022 (10:44:13 CEST)
The low water solubility of any pharmacoactive molecules limits their pharmacological potential but the solubility parameter cannot compromise, so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, the oral dosage forms cover more than 50 %, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry screening programs identified that around 40% of new chemical entities (N.C.E.s) face various difficulties at the formulation and development step. These pharmaceuticals are attributed to their less solubility and bioavailability. The bioavailability and drug solubility enhancement are significant challenges in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibits poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of the poorly water-soluble drug, for example, complexation of active molecules, utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelles preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, by some appropriate research reports.
REVIEW | doi:10.20944/preprints202102.0205.v1
Subject: Life Sciences, Biochemistry Keywords: Beta-carotene; bioavailability; delivery system; encapsulation; engineered nanomaterial; SLNs; NLCs
Online: 8 February 2021 (12:31:57 CET)
Accruing evidence on the influence of β-carotene regarding the prevention of several chronic diseases - in addition to its well-acknowledged role in vision has been a strong driver for developing alternative delivery systems. Though oral delivery is accepted as the most fitting, mild and safe path for delivering bioactive agents, β-carotene delivery via food items poses challenges due to its lipophilic nature, poor water-solubility, high chemical/photochemical instability and poor oral bioavailability. Nanotechnology has opened new windows for delivering bioactive agents. Their physiochemical characteristics, i.e. small size, high surface area, unique composition, biocompatibility and biodegradability make these nanomaterials an attractive tool for β-carotene delivery. Delivering β-carotene through nanoparticles does not only improve its bioavailability/bioaccumulation in target tissues, but also lessens its sensitivity against environmental factors during processing. Regardless of these benefits, nanocarriers inherit some limitations, such as variations in sensory quality, modification of the food matrix, increasing costs, as well as limited consumer acceptance and regulatory challenges. This research area has been rapidly evolved, with a plethora of innovative nano-engineered materials, including micelles, nano/microemulsion, liposomes, niosomes, solid-lipid nanoparticles and nanostructured lipid carriers. These nano-delivery systems make conventional delivery systems appear archaic and promise better solubilization, protection during processing, improved shelf-life, higher bioavailability as well as controlled and targeted release. This review provides information on the state of knowledge on β-carotene nano-delivery systems adopted for developing functional foods: depicting their classification, composition, preparation methods, challenges, release-and absorption of β-carotene in the GIT and possible risks and future prospects.
ARTICLE | doi:10.20944/preprints201807.0498.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: bioavailability; Fe; nitrogen deficiency; phosphorous deficiency; phytic acid; wheat; Zn
Online: 26 July 2018 (03:40:56 CEST)
Iron (Fe) and zinc (Zn) deficiency in cereal grains has deleterious effects on the health of millions of people, especially in developing countries. As wheat, as a staple crop, is consumed in large quantities, its micronutrient content is important. Crops in Africa are often grown under low nitrogen (N) and low phosphorous (P) conditions. The aim of this study was to determine the effect of low N and low P stress on Fe and Zn and phytic acid concentration, in two commercial spring wheat cultivars with excellent baking quality. The two cultivars did not differ significantly for the measured characteristics. Across all treatments the average values for Fe varied between 19.60-28.61 mg kg-1, Zn between 17.68-33.79 mg kg-1 and phytic acid between 5.03-6.92 mg g-1. Low P stress lead to the highest values of Fe and Zn, and the lowest value for phytic acid. Phytic acid:Fe and phytic acid:Zn ratios were also highly significantly reduced under low P stress conditions. Low N conditions caused significantly increased Zn levels. Despite this, the phytic acid:Fe and phytic acid:Zn ratios were relatively high under all conditions, indicating a low bioavailability of both Fe and Zn in these wheat cultivars.
REVIEW | doi:10.20944/preprints202103.0419.v1
Subject: Chemistry, Analytical Chemistry Keywords: Resveratrol; Cardiovascular disease; Bioavailability; Diet; COVID-19; Resveratrol carriers; Cardiovascular protection
Online: 16 March 2021 (12:00:17 CET)
Resveratrol is a phytoalexin produced by many plants as a defense mechanism against stress-inducing conditions. The richest dietary sources of resveratrol are berries and grapes, their juices and wines. Good bioavailability of resveratrol is not reflected in its high biological activity in vivo because of resveratrol isomerization and its poor solubility in aqueous solutions. Proteins, cyclodextrins and nanomaterials have been explored as innovative delivery vehicles for resveratrol to overcome this limitation. Numerous in vitro and in vivo studies demonstrated beneficial effects of resveratrol in cardiovascular diseases (CVD). Main beneficial effects of resveratrol intake are cardioprotective, anti-hypertensive, vasodilatory, anti-diabetic, and improvement of lipid status. As resveratrol can alleviate the numerous factors associated with CVD, it has potential as a functional supplement to reduce COVID-19 illness severity in patients displaying poor prognosis due to cardio-vascular complications. Resveratrol was shown to mitigate the major pathways involved in the pathogenesis of SARS-CoV-2 including regulation of the renin-angiotensin system and expression of angiotensin-converting enzyme 2, stimulation of immune system and downregulation of pro-inflammatory cytokines release. Therefore, several studies already have anticipated potential implementation of resveratrol in COVID-19 treatment. Regular intake of resveratrol rich diet, or resveratrol-based complementary medicaments, may contribute to a healthier cardio-vascular system, prevention and control of CVD, including COVID-19 disease related complications of CVD.
ARTICLE | doi:10.20944/preprints201812.0059.v1
Subject: Medicine & Pharmacology, Other Keywords: Bioavailability; Box-Behnken design; β-cyclodextrin; erectile dysfunction; taste masking; vardenafil.
Online: 4 December 2018 (16:39:51 CET)
Because of lower solubility and considerable metabolism, vardenafil (VRD) bioavailability is 15 %. To get over this obstacle, this study aimed to increase the solubility, hasten the onset of action, and mask the unpleasant taste of VRD utilizing β-cyclodextrin (β-CD) and formulation of the inclusion complex as oral disintegrating tablets (ODTs). The solubility of the obtained complexes in various ratios has been studied. A Box-Behnken design (BBD) was utilized to investigate the influence of excipients on the quality of ODTs. The solubility of VRD was improved at 1:2 drug: β-CD ratio. The formulated VRD-ODTs exhibited satisfying results regarding the hardness and disintegration time. In addition, in vivo taste masking and disintegration time showed improved results, after placing the tablets in the oral cavity of the healthy volunteers. The pharmacokinetic parameters for the optimized VRD–ODTs exhibited a significant improvement with P < 0.05 in the maximum plasma concentration and reduction in the time needed to reach this concentration when compared with the marketed tablets. Finally, the optimized VRD-ODTs exhibited increased oral absorption of VRD and subsequent decreasing the time of onset of clinical effect and masking the unpleasant taste, which is favored for patients with erectile dysfunction.
ARTICLE | doi:10.20944/preprints201809.0465.v1
Subject: Life Sciences, Other Keywords: Phaseolus vulgaris L., yellow beans, Manteca, cooking time, iron, bioavailability, polyphenols
Online: 24 September 2018 (15:24:38 CEST)
The common dry bean (Phaseolus vulgaris L.) is a nutrient dense food produced globally as a major pulse crop for direct human consumption, and is an important source of protein and micronutrients for hundreds of millions of people across Latin America, the Caribbean and Sub-Saharan Africa. Beans require large amounts of heat energy and time to cook, deterring consumers worldwide from purchasing beans. In regions where consumers rely on expensive fuelwood for food preparation, the yellow bean is often marketed as fast cooking. A Yellow Bean Panel (YBP) was assembled to explore the cooking time and health benefits of the five major seed types within the yellow bean market class (Amarillo, Canary, Manteca, Mayocoba, Njano) over two field seasons. This study shows how the Manteca yellow bean possess a fast cooking phenotype, which could serve a genetic resource for introducing fast cooking properties into a new generation of dry beans with cooking times < 20 minutes when pre-soaked and < 80 minutes unsoaked. Nutritional evaluation revealed fast cooking yellow beans have high iron retention (>80%) after boiling. An in vitro digestion/Caco-2 cell culture bioassay revealed a strong negative association between cooking time and iron bioavailability in the YBP (r values > -0.73). When either pre-soaked or left unsoaked the highest iron bioavailability scores were measured in the fast cooking Manteca genotypes providing evidence that this yellow market class is worthy of germplasm enhancement through the added benefit of improved iron quality after cooking.
ARTICLE | doi:10.20944/preprints201807.0154.v1
Subject: Biology, Plant Sciences Keywords: bread wheat; correlations, gamma, grain nutrients concentrations; mutation, phytic acid; metals bioavailability
Online: 9 July 2018 (15:39:51 CEST)
Metal, primarily Fe and Zn, deficiencies affect over half of the world's population. Human diets with prevalent cereal products cause micronutrient malnutrition. Biofortification is one of the most effective approaches to alleviate malnutrition. Spring wheat genetically stable (M7) mutant lines developed with 100 and 200 Gy gamma treatments to broaden genetic variation and search for new resources were analyzed for nutritionally important minerals (Ca, Mg, K, Fe, and Zn), their bioavailability, and grain protein content (GPC). The variation was 172.3–883.0 mg/kg for Ca, 472.9–1088 mg/kg for Mg, 3128.6–5487.5 mg/kg for K, 40.9–89.0 mg/kg for Fe, and 22.2–89.6 mg/kg for Zn. In mutant lines, among the investigated minerals, the highest increases in concentrations were observed in Fe, Zn, and Ca when compared to the parent. Some mutant lines, mostly in the 100 Gy-derived germplasm, had two to three times higher Fe, Zn, and Ca concentrations, lower phytic acid concentration (1.4–2.1 times), and 6.5–7% higher GPC compare to the parent. Variation was detected for the Ca:Phy, Mg :Phy, Phy:K, Phy:Fe, and Phy:Zn molar ratios, (1.27–10.41, 5.05–18.68, 1.66–4.87, 1.40–5.32 and 1.78–11.78, respectively). The results showed how the genetic variation could be generated through radiation and be useful to develop biofortification by micronutrient varieties with their appropriate bioavailability to overcome malnutrition.
COMMUNICATION | doi:10.20944/preprints201611.0127.v1
Subject: Earth Sciences, Environmental Sciences Keywords: persistent organic pollutants, bioavailability, Diffusive Gradient Thin film (DGT), passive probe, degradation
Online: 25 November 2016 (09:59:08 CET)
The present study describes the activities performed to test a new method for measuring the mobility of polycyclic aromatic hydrocarbons (PAHs) in the solid phase of sediments within the context of environmental pollution risk assessment. The method is based on the design of a new configuration (new materials) of the commercial passive sampler Chemcatcher as probe for predicting the bioavailability of persistent organic pollutants in marine sediments (or in water saturated soils).
ARTICLE | doi:10.20944/preprints202008.0690.v1
Subject: Chemistry, General & Theoretical Chemistry Keywords: Theopapuamides A-D; Virtual Screening; Chemoinformatics; Conceptual DFT; Computational Peptidology; Bioavailability; Bioactivity Scores; ADMET
Online: 31 August 2020 (03:57:38 CEST)
This work presents the results of a computational study of the chemical reactivity and bioactivity properties of the members of the Theopapuamides A-D family of marine peptides by making use of our own proposed methodology named Computational Peptidology (CP) that has been successfully considered in previous studies of this kind of molecular systems. CP allowed for the determination of the global and local descriptors that come from Conceptual Density Functional Theory (CDFT) that can give an idea of the chemical reactivity properties of the marine natural products under study which are already known to be related to their bioactivity. At the same time, the validity of the procedure based on the adoption of the KID (Koopmans in DFT) technique as well as the MN12SX/Def2TZVP/H2O model chemistry has been successfully verified. Together with several Chemoinformatic tools that can be used for the improvement of process of Virtual Screening, some additional properties of these marine peptides were identified related to their ability to behave as useful drugs. With the further object of analyzing their bioactivity some parameters of usefulness for future QSAR studies, their predicted biological targets and the the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) parameters related to the Theopapuamides A-D pharmacokinetics are also reported.
REVIEW | doi:10.20944/preprints202106.0305.v1
Subject: Medicine & Pharmacology, Allergology Keywords: dietary flavonoids; cardioprotective effects; ROS scavenging; myocardial dysfunction; bioavailability and drug metabolism; toxicity; drug discovery
Online: 11 June 2021 (08:44:01 CEST)
Flavonoids comprise a large group of structurally diverse polyphenolic compounds of plant origin and are abundantly found in human diet such as fruits, vegetables, grains, tea, dairy products, red wine and so on. Major classes of flavonoids include flavonols, flavones, flavanones, flavanols, anthocyanidins, isoflavones, and chalcones. Owing to their potential health benefits and medicinal significance, flavonoids are now considered as an indispensable component in a variety of medicinal, pharmaceutical, nutraceutical, and cosmetic preparations. However, flavonoids play a significant role in preventing cardiovascular diseases (CVDs), which could be mainly due to their antioxidant, antiatherogenic, and antithrombotic effects. Epidemiological and in vitro/in vivo evidences of antioxidant effects support the cardioprotective function of dietary flavonoids. Further, the inhibition of LDL oxidation and platelet aggregation following regular consumption of food containing flavonoids and moderate consumption of red wine might protect against atherosclerosis and thrombosis. A study suggests that daily intake of 100 mg of flavonoids through diet may reduce the risk of developing morbidity and mortality due to coronary heart disease (CHD) by approximately 10%. This review summarizes dietary flavonoids with their sources and potential health implications in CVDs including various redox-active cardioprotective (molecular) mechanisms with antioxidant effects. Pharmacokinetic (oral bioavailability, drug metabolism), toxicological and therapeutic aspects of dietary flavonoids are also addressed herein with future directions for the discovery and development of useful drug candidates/ therapeutic molecules.
REVIEW | doi:10.20944/preprints202008.0223.v1
Subject: Chemistry, Inorganic & Nuclear Chemistry Keywords: Serum transferrin; endocytosis; nonferric metal ions; metal transport, bioavailability, and bioactivity; metal therapeutic function and toxicity
Online: 9 August 2020 (21:47:51 CEST)
Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding, blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.
ARTICLE | doi:10.20944/preprints202008.0351.v1
Subject: Chemistry, General & Theoretical Chemistry Keywords: discodermins A-H; chemical reactivity theory; conceptual DFT; global and local reactivity descriptors; pKa; bioavailability; bioactivity scores; ADME
Online: 17 August 2020 (04:45:58 CEST)
A methodology based on the concepts that arise from Density Functional Theory named Conceptual Density Functional Theory (CDFT) was chosen for the calculation of some global and local reactivity descriptors of the Discodermins A-H family of marine peptides through the consideration of the KID (Koopmans in DFT) technique that was successfully used in previous studies of this kind of molecular systems. The determination of active sites of the studied molecules for different kind of reactivities was achieved by resorting to some CDFT-based descriptors like the Fukui functions as well as the Parr functions derived from Molecular Electron Density Theory (MEDT). A few properties identified with their ability to behave as a drug and the bioactivity of the peptides considered in this examination were acquired by depending on a homology model by studying the correlation with the known bioactivity of related molecules in their interaction with various biological receptors. With the further object of analyzing their bioactivity some parameters of usefulness for future QSAR studies, their predicted biological targets and the the ADME (Absorption, Distribution, Metabolism, and Excretion) parameters related to the Discodermins A-H pharmacokinetics are also reported.
REVIEW | doi:10.20944/preprints201904.0162.v1
Subject: Materials Science, Nanotechnology Keywords: silymarin; silybin; nanoemulsion; solid lipid nanoparticles; nanostructured lipid carriers; liposome; polymeric particles; self-emulsifying delivery systems; enhanced bioavailability
Online: 15 April 2019 (11:23:17 CEST)
Silymarin, a mixture of flavonolignan and flavonoid polyphenolic compounds extractable from the milk thistle seed, Silybum marianum, has anti-oxidant, anti-inflammatory, anti-cancer and anti-viral activities potentially useful in the treatment of several liver disorders, such as chronic liver diseases, cirrhosis and hepatocellular carcinoma. Equally promising are the effects of silymarin in protecting the brain from the inflammatory and oxidative stress effects by which metabolic syndrome contributes to neurodegenerative diseases. However, despite clinical trials have proved that silymarin is safe at high doses (>1500 mg/day) in humans, it suffers limiting factors such as low solubility in water (<50 μg/mL), low bioavailability and poor intestinal absorption. To improve its bioavailability and provide a prolonged silymarin release at the site of absorption, the use of nanotechnological strategies appears to be a promising method to potentiate the therapeutic action and promote sustained release of the active herbal extract. The purpose of this study is to review the different nanostructured systems available in literature as delivery strategies to improve the absorption and bioavailability of silymarin.