REVIEW | doi:10.20944/preprints201608.0160.v2
Subject: Medicine & Pharmacology, Nutrition Keywords: cranberry; cancer; proanthocyanidin; quercetin; ursolic acid
Online: 18 August 2016 (07:44:23 CEST)
Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques; whereas, in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy will be considered
ARTICLE | doi:10.20944/preprints202008.0025.v1
Subject: Chemistry, Analytical Chemistry Keywords: HPLC method; Curcumin; Quercetin; Thermal analysis; Nanoemulsion
Online: 2 August 2020 (12:15:13 CEST)
Biphasic oily/water nanoemulsions have been proposed as delivery systems for the intranasal administration of curcumin (CUR) and quercetin (QU), due to their high drug entrapment efficiency, the possibility of simultaneous drug administration and protection of the encapsulated compounds from the degradation. To better understand the physicochemical and biological performance of the selected formulation simultaneously co-encapsulating CUR and QU, a stability test of the compounds mixture was firstly carried out using X-ray powder diffraction and thermal analyses, such as differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA). The determination and quantification of the encapsulated active compounds was then required being an essential tool for the development of innovative nanomedicines. Thus, a new HPLC–UV/Vis method for the simultaneous determination of CUR and QU in the nanoemulsions and their evaluation in stability studies in simulated biological fluids was developed and validated. The X-ray diffraction analyses demonstrated that no interaction between the mixture of active ingredients, if any, is strong enough to take place in the solid state. Moreover, the thermal analysis demonstrated that the CUR and QU are stable in the nanoemulsion production temperature range. The proposed analytical method for the simultaneous quantification of the two actives was selective and linear for both compounds in the range of 0.5 – 12.5 µg/mL (R2 > 0.9997), precise (RSD below 3%), robust and accurate (recovery 100 ± 5 %). The method was validated in accordance with ICH Q2 R1 “Validation of Analytical Procedures” and CDER-FDA 2validation of chromatographic methods” guideline. Furthermore, the low detection (LOD < 0.005 µg/mL for CUR and <0.14 µg/mL for QU) and quantification limits (LOQ < 0.017 µg/mL for CUR and < 0.48 µg/mL for QU) of the method were suitable for the application to drug release and permeation studies planned for the development of the nanoemulsions. The method was then applied for the determination of nanoemulsions CUR and QU encapsulation efficiencies (> 99%), as well as for the stability studies of the two compounds in simulated biological fluids over time. The proposed method represents, to our knowledge, the only method for the simultaneous quantification of CUR, and QU in nanoemulsions.
REVIEW | doi:10.20944/preprints202208.0205.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: Cholesterol efflux; flavonoids; HDL; quercetin; reverse cholesterol transport
Online: 11 August 2022 (03:33:47 CEST)
One of the mechanisms used in the management and cure of atherosclerosis is reverse cholesterol transfer (RCT), which plays a vital role in the export of cholesterol from peripheral cells. Cholesterol efflux from macrophages in the subintima of the vessel wall is a critical part of RCT. ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) are involved in the transfer of cholesterol from arterial macrophages to extracellular high-density lipoprotein cholesterol (HDL). The HDL then transports esterified cholesterol to the liver for elimination. An important factor in the reverse cholesterol transport and excretion of extracellular cholesterol is HDL. Atherogenesis can be prevented by altering the processes of RCT and cholesterol efflux, and this might lead to novel treatment options for cardiovascular disease. Research of novel modifying variables for RCT and cholesterol efflux is necessary. A better understanding of RCT's molecular processes has been gained via research, allowing for the creation of new treatments that make use of RCT's potential for pharmacological improvement. The purpose of this review is to provoke discussion on the potential impact of selected flavonoids on cholesterol efflux on the progression of atherosclerosis (Fig. 1.).
ARTICLE | doi:10.20944/preprints202101.0481.v1
Subject: Materials Science, Biomaterials Keywords: Antibacterial activity; Endodontic irrigant; Enterococcus faecalis; Quercetin; Root canal
Online: 25 January 2021 (10:54:58 CET)
(1) Background: Bacterial reinfection and root fracture are the main culprits related to root canal treatment failure. This study aimed to assess the utility of quercetin solution as an adjunctive endodontic irrigant that strengthen root canal dentin with commitment anti-biofilm activity and bio-safety. (2) Methods: Based on a noninvasive dentin infection model, dentin tubules infected with Enterococcus faecalis (E. faecalis) were irrigated with sterile water (control group), and 0, 1, 2, 4 wt% quercetin-containing ethanol solutions. The live and dead bacteria proportions within E. fae-calis biofilms were analyzed using confocal laser scanning microscopy (CLSM). Elastic modulus and hydroxyproline release and X-ray photoelectron spectroscopy (XPS) characterization was tested on irrigant-treated demineralized dentin to evaluate irrigants’ biostability. The cytotoxicity of irrigants was tested by CCK-8 assay. (3) Results: Quercetin increased the proportion of dead bacteria volumes within E. faecalis, and improved the flexural strength of dentin collagen com-pared to control group. The XPS characterization revealed an increase in C-O peak area under both C1s and O1s narrow-scan spectra. The CCK-8 assay confirmed no cytotoxicity of quercetin solutions. (4) Conclusions: Quercetin exhibited anti-biofilm activity, collagen-stabilizing effect as well as cytocompatibility, supporting quercetin as a potential candidate for endodontic irrigant.
ARTICLE | doi:10.20944/preprints202012.0268.v1
Subject: Chemistry, Analytical Chemistry Keywords: Oenothera biennis; standardization; quercetin 3-glucuronide; ellagic acid; method validation
Online: 10 December 2020 (16:43:01 CET)
Toward the standardization of O. biennis sprout extract (OBS-E), we aimed to obtain indicator compounds, using a validated method. HPLC-UVD allowed simultaneous quantification of indicator compounds quercetin 3-glucuronide and ellagic acid. The method was validated in terms of specificity, linearity, precision, accuracy, and limit of detection/limit of quantification (LOD/LOQ). High specificity and linearity was demonstrated, with correlation coefficients of 1.0000 for quercetin 3-glucuronide and 0.9998 for ellagic acid. The LOD/LOQ values were 0.486/1.472 μg/mL for quercetin 3-glucuronide and 1.003/3.039 μg/mL for ellagic acid. Intra-day and inter-day variability tests produced relative standard deviation for each compound of <2%, a generally accepted precision criterion. High recovery rate were also obtained, indicating accuracy validation. The OBS-E prepared using various concentrations of ethanol were then analyzed. The 50% ethanol extract had highest content of quercetin 3-glucuronide, whereas the 70% ethanol extract possessed the lowest. However, the ellagic acid content was highest in the 70% ethanol extract and lowest in the 90% ethanol extract. Thus, quercetin 3-glucuronide and ellagic acid can be used industrially as indicator compounds for O. biennis sprout products, and our validated method can be used to establish indicator compounds for other natural products.
ARTICLE | doi:10.20944/preprints201904.0156.v1
Subject: Life Sciences, Other Keywords: quercetin; eugenol; organic compounds; rumen; environment; HPLC-DAD; polyphenols-containing plants
Online: 13 April 2019 (05:23:35 CEST)
This study had the objective to evaluate the effect of Piper betle L. powder (PP) at 5 different doses in substrate incubated by sunflower oil as secondary function of PUFA using in vitro gas production technique. The treatments of this study were run as a 2X5 factorial arrangement in a completely randomised design using the PROC GLM procedure of SAS 9.4: (1) control (S1) without supplementation of PP; (2) 15 mg PP (S2); (3) 30 mg PP (S3); (4) 45 mg PP (S4); and (5) 60 mg PP (S5), while sunflower oil was supplemented in all treatments: low 15 mg/incubation and high 30 mg/incubation. A 500 mg of TMR (hay: concentrate, 50:50) was assigned to basal substrate. The PP containing 1.84 mg/g DM quercetin and 1.00 mg/g DM eugenol altered rumen fermentation without change pH (p < 0.001) and methane production was lesser (p < 0.001) about -30% and -25% for DM and OM measurement, respectively. Gas kinetic, degradability, and ammonia level was significantly affected by supplementing PP (p < 0.01). Overall, this study suggested quercetin and eugenol deriving from PP acted three major accelerations: assembled carbon dioxide, behaved antimicrobial role and performed the balance water molecules in the rumen kinetic. This study suggests that PP promotes changing in vitro rumen fermentation and diminishing methane production within recommended doses, 0.1-15 mg/incubation in DM.
ARTICLE | doi:10.20944/preprints201806.0341.v1
Subject: Life Sciences, Molecular Biology Keywords: Kummerowia striata; anti-oxidant activity; melanin synthesis; p-coumaric acid; quercetin
Online: 21 June 2018 (14:44:02 CEST)
Kummerowia striata is a traditional medicine used for the therapy of inflammation-related diseases. Herein, we investigated the anti-melanogenic and antioxidant activities of an ethanolic extract of K. striata (EKS) using a number of in vitro and cell culture model systems. The anti-melanogenic effect was assessed in B16F10 melanoma cells based on melanin synthesis and in vitro tyrosinase inhibitory activity and the anti-oxidant activity assays were performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS); EKS exhibited strong anti-oxidant activities in both the assays. The expression of tyrosinase, tyrosinase-related protein 1, tyrosinase-related protein 2, and microphthalmia-associated transcription factor was decreased in a dose-dependent manner at mRNA and protein levels upon treatment with EKS. Notably, EKS did not affect the cell viability at all the EKS concentrations used in this study, indicating that EKS-mediated inhibition of melanin synthesis is not accompanied with cytotoxicity. Collectively, our findings demonstrate, for the first time, that EKS possesses anti-melanogenic and anti-oxidant activities, and suggest that further evaluation and development of EKS as a functional supplement or cosmetic might be useful for skin whitening and for reduction wrinkles.
ARTICLE | doi:10.20944/preprints201911.0244.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: activated inflammatory macrophages; quercetin; pro-/anti-inflammatory cytokine genes; STAT3 protein phosphorylation; TLR2
Online: 20 November 2019 (16:04:42 CET)
Our previous studies demonstrated that quercetin (Q) could be ingested and metabolized by macrophages and exerted prophylactic immuno-stimulatory activity and therapeutic anti-inflammatory effects on lipopolysaccharide (LPS)-treated macrophages ex vivo. To further clarify its possible anti-inflammatory mechanism, Q was selected to treat mouse peritoneal macrophages that obtained from female BALB/c mice exposed to LPS i.p. for 12 h. Relative gene expression of pro-/anti-inflammatory (TNF-α/IL-10) cytokines and components of inflammation-related intracellular signaling pathways (TLR2, TLR4, NF-κB, JAK2 and STAT3) was analyzed using two-step reverse transcription (RT) and real-time quantitative polymerase chain reaction (qPCR). STAT3 protein phosphorylation was determined using an in-cell ELISA method. As a result, Q and its metabolite quercetin-3-O-β-D-glucuronide (Q3G) decreased TNF-α gene expression amounts and ratios of pro-/anti-inflammatory (TNF-α/IL-10) cytokine gene expressions, but increased IL-10 gene expression amounts in activated inflammatory macrophages, supporting a substantial anti-inflammatory potential of Q and Q3G treatments. However, Q3G had lower effects than those of Q. Importantly, Q inhibited TLR2 gene expression and phosphorylation of STAT3 protein in the inflamed cells. Our results are the first report to suggest that Q inhibits LPS-induced inflammation ex vivo through suppressing TLR2 gene expression and STAT3 protein phosphorylation in activated inflammatory macrophages. Q has potential to further apply for treating inflammation-associated diseases.
ARTICLE | doi:10.20944/preprints201901.0041.v1
Subject: Biology, Physiology Keywords: nonalcoholic fatty liver disease; high fat-sucrose diet; metabolomics; HPLC-QTOF-MS; quercetin
Online: 4 January 2019 (14:04:13 CET)
As metabolomics is widely used in the study of disease mechanisms, more and more studies have found that metabolites play an important role in the occurrence of diseases. The aim of this study is to investigate the effects and mechanisms of quercetin in high-fat-sucrose diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) development using nontargeted metabolomics. A rat model of NAFLD was established by feeding with a HFD for 30 and 50 days. Results indicated quercetin exhibited hepatoprotective activity in HFD-induced NAFLD rats in 30 days by regulating fatty acids related metabolites (adrenic acid, etc.), inflammation related metabolites (arachidonic acid, etc.), oxidative stress related metabolites (2-hydroxybutyric acid) and other differential metabolites (citric acid, etc.). However, quercetin couldn’t improve NAFLD in 50 days maybe it couldn’t reverse the inflammation condition induced by long-term high-fat diet. These data indicate that dietary quercetin may be beneficial to NAFLD at early stages. Furthermore, combining metabolomics and experimental approaches opens up avenues of effects and mechanisms of drugs for complex diseases.
SHORT NOTE | doi:10.20944/preprints201806.0454.v1
Subject: Chemistry, Organic Chemistry Keywords: Pancreatic Porcine Lipase, Regio-selectivity; Quercetin derivatives, Oleic acid, ecofriendly reaction, scalable process.
Online: 27 June 2018 (16:01:26 CEST)
Polyphenols are well-known health promoting agents, but they have some limitations due to their spontaneous oxidation. This evidence has limited their use as drugs in the last years. In this field, several chemical modifications have been proposed to overcome these restrictions; among these, the esterification seems to be the preferred. Ester derivatives could be able to reduce the bioavailability problems connected to polyphenols. On the other hand, the presence of the esterase enzymes in the body guarantees the ester hydrolysis, which in turn frees the two molecules that make it up. Lipase-catalyzed esterifications afforded several derivatives of flavonoids glycosides, in green conditions. In this short note, pancreatic porcine lipase was firstly used as a cheap bio-catalyst, to synthesize oleoyl derivatives of quercetin in aglycone form. Results demonstrated how the enzyme acyl regioselective in position C-3, with high yields and easy purification processes
ARTICLE | doi:10.20944/preprints202103.0675.v1
Subject: Biology, Anatomy & Morphology Keywords: Fruit ripening; gingerglycolipid A; HPLC-HRMS; melatonin; nitric oxide; phytosphingosin; quercetin; transcriptomics; L-tryptophan
Online: 26 March 2021 (15:44:51 CET)
Plant species are precursors of a wide variety of secondary metabolites that, besides having useful activity for themselves, can also be used by humans for their consumption and economic benefit. Pepper (Capsicum annuum L.) fruit is not only a common food and spice source, but it also stands out for containing high amounts of antioxidants (such as vitamins C and A), polyphenols and capsaicinoids. Particular attention has been paid to capsaicin, whose anti-inflammatory, antiproliferative and analgesic activities, have been proven. Due to the potential interest in pepper metabolites for human use, in this project, we carried out an investigation to identify new bioactive compounds of this crop is carried out. To achieve this, we developed a metabolomic approach, using an HPLC (high-performance liquid chromatography) separative technique coupled to metabolite identification by high resolution mass spectrometry (HRMS). After chromatographic analysis and data processing against metabolic databases, 12 differential bioactive compounds were identified in sweet pepper fruits, including quercetin and its derivatives, L-tryptophan, phytosphingosin, FAD, gingerglycolipid A, tetrahydropentoxylin, blumenol C glucoside, colnelenic acid and capsoside A. The abundance of these metabolites varied depending on the ripening stage of the fruits, either immature green or ripe red. We also studied the variation of these 12 metabolites upon treatment with exogenous nitric oxide (NO), a free radical gas involved in a good number of physiological processes in higher plants such as germination, growth, flowering, senescence, and fruit ripening, among others. Overall, it was found that the content of the analysed metabolites was modulated by the ripening stage and by the presence of NO. The metabolic pattern followed by quercetin and its derivatives, as a consequence of the ripening stage and NO treatment, was also corroborated by transcriptomic analysis of genes involved in the synthesis of these compounds. This opens new research windows on the pepper fruit’s bioactive compounds with nutraceutical potentiality, where biotechnological strategies can be applied for optimizing the level of these beneficial compounds.
ARTICLE | doi:10.20944/preprints201904.0177.v1
Subject: Chemistry, Other Keywords: lipid peroxidation; membrane elasticity; mesoporous silica nanoparticles; myricetin; myricitrin; nanomechanics; protective effects of flavonoids; quercetin
Online: 16 April 2019 (09:54:03 CEST)
Flavonoids, polyphenols with anti-oxidative activity have high potential as novel therapeutics for neurodegenerative disease, but their applicability is rendered by their poor water solubility and chemical instability under physiological conditions. In this study, this is overcome by delivering flavonoids to model cell membranes (unsaturated DOPC) using prepared and characterized biodegradable mesoporous silica nanoparticles, MSNs. Quercetin, myricetin and myricitrin have been investigated in order to determine the relationship between flavonoid structure and protective activity towards oxidative stress i.e. lipid peroxidation induced by addition of hydrogen peroxide and/or Cu2+ ions. Among investigated flavonoids, quercetin showed the most enhanced and prolonged protective anti-oxidative activity. The nanomechanical (Young modulus) measurement of the MSNs treated DOPC membranes during lipid peroxidation confirmed attenuated membrane damage. By applying combination of experimental techniques (AFM, force spectroscopy, ELS, DLS), this work generated detailed knowledge about the effects of flavonoid loaded MSNs on the elasticity of model membranes, especially under oxidative stress conditions. Results from this study will pave the way towards the development of innovative and improved markers for oxidative stress-associated neurological disorders. In addition, the obtained could be extended to designing effective delivery systems of other high potential bioactive molecules with an aim to improve human health in general.
REVIEW | doi:10.20944/preprints202207.0118.v1
Subject: Life Sciences, Other Keywords: Eyes diseases; Oxidative damage; Antioxidant compounds; Vitamin A; Vitamin C; Lutein; Curcumin; Quercetin; Coenzyme Q10; PUFAs; BPF; Grape seed
Online: 7 July 2022 (09:04:14 CEST)
Abstract Eye health is crucial and the onset of diseases can reduce vision and affect the quality of life of patients. The main causes of progressive and irreversible vision loss include various pathologies such as cataracts, ocular atrophy, corneal opacity, age-related macular degeneration, uncorrected refractive error, posterior capsular opacification, uveitis, glaucoma, diabetic retinopathy, retinal detachment, undetermined disease and other disorders involving oxidative stress and inflammation. The eyes are constantly exposed to the external environment and, for this reason, must be protected from damage from the outside. Many drugs, including cortisonics and antinflammatory drugs have widely been used to counteract eye disorders. However, recent advances have been obtained via supplementation of patients with natural antioxidants and nutraceuticals. In particular, evidence has been accumulated that polyphenols (mostly deriving from Citrus Bergamia) represent a reliable source of antioxidants able to counteract oxidative stress accompanying early stages of eye diseases. Luteolin, in particular, has been found to protect foto-receptors thereby improving vision in many disease states. Moreover, a consistent anti-inflammatory response was found to occur when curcumin is used alone or in combination with other nutraceuticals. On the other hand, CoQ10 has been demonstrated to produce consistent effect in reducing ocular pressure thereby leding to protection in patients undergoing glaucoma. Finally, both grape seed extract rich in anthocyanosides and polynsatured fatty acids (PUFAs) seem to contribute in the prevention of retinal disorders. Thus, combination of nutraceuticals and anti-oxidants may represent the right solution for a multiaction activity in eye protection to be associated to current drug therapies, and this will be of potential interest in early stages of eye disorders.
Subject: Chemistry, Other Keywords: bioactive compounds from European trees and shrubs; gallic and cinnamic acids; quercetin; pinosylvin; β–sitosterol; alfa- and β-pinene
Online: 28 October 2019 (11:57:17 CET)
Plants produce specific structures constituting a barrier hindering penetration of pathogens, while they also produce substances inhibiting pathogen growth . These compounds are secondary metabolites, such as phenolics, terpenoids, sesquiterpenoids, resins, tannins and alkaloids. Bioactive compounds are secendary metabolities from trees and shrubs are used in medicine, herbal medicine and cosmetology. To date fruits and flowers of exotic trees and shrubs have been primarily used as sources of bioactive compounds. In turn, search for new sources of bioactive compounds is currently focused on native plant species due to its availability. Application of such raw material needs to be based on knowledge of their chemical composition, particularly health-promoting or therapeutic compounds. Research conducted to date on European trees and shrubs has been scarce. This paper presents results of literature studies conducted to systematise knowledge on bioactive compounds found in trees and shrubs native to central Europe. The aim of this review providing available information on the subject is to indicate gaps in the present knowledge.