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Uporedno spektrofotometrijsko ispitivanje ukupnog sadržaja fenola i antioksidativnog kapaciteta merenih DPPH i ABTS metodama u zelenom povrću
No full textModern trends in nutrition imply the daily intake of fresh fruits and vegetables, with the
statement that they are important sources of natural antioxidants that protect the body from
oxidative stress and can contribute to the prevention of many chronic diseases. In these
recommendations, green vegetables with high total phenolics content (TPC) are especially
highlighted. However, one must ask whether the high total phenolics content of green vegetables,
such as Brussels sprouts, cabbage, broccoli, parsley, borecole and spinach, is a reliable indicator
of antioxidant activity for regulating free radicals in the body. The aim of this work is the
spectrophotometric determination of TPC of hydromethanol extracts of selected green vegetables
and its correlation with their antioxidant potential. For this purpose, DPPH and ABTS radical
scavenging tests of extracts were performed. The obtained results indicate that Brussels sprouts
and parsley exhibit the highest antioxidative activities, while cabbage extract shows lower values.
The Pearson correlation used to test the correlation between the TPC obtained for green vegetable
extracts and the results of the DPPH and ABTS tests shows a moderate correlation between TPC
and ABTS values, whereas the correlation for TPC and DPPH is statistically significant.Savremeni trendovi u ishrani podrazumevaju svakodnevni unos svežeg voća i povrća, uz
konstataciju da su oni važni izvori prirodnih antioksidanata koji štite organizam od oksidativnog
stresa i mogu doprineti prevenciji mnogih hroničnih bolesti. U ovim preporukama posebno se
ističe zeleno povrće sa visokim ukupnim sadržajem fenola (TPC). Međutim, mora se postaviti
pitanje da li je visok ukupan sadržaj fenola u zelenom povrću, kao što su prokelj, kupus, brokoli,
peršun, kelj i spanać, pouzdan pokazatelj antioksidativne aktivnosti za regulisanje slobodnih
radikala u organizmu. Cilj ovog rada je spektrofotometrijsko određivanje TPC i utvrđivanje
korelacije između TPC i antioksidativnog potencijala metanol-vodenih ekstrakata odabranog
zelenog povrća. U tu svrhu sa ekstraktima povrća urađeni su DPPH i ABTS testovi uklanjanja
radikala. Dobijeni rezultati ukazuju na to da prokelj i peršun pokazuju najveću antioksidativnu
aktivnost, dok ekstrakt kupusa pokazuje niže vrednosti. Pirsonova korelacija koja je korišćena za
testiranje korelacije između TPC dobijene za ekstrakte zelenog povrća i rezultata DPPH i ABTS
testova pokazuje umerenu korelaciju između vrednosti TPC i ABTS, dok je korelacija za TPC i
DPPH statistički značajna
Theoretical insight into redox properties of 9-Acridinyl amino acid derivatives
No full textThe redox properties of 9-acridinyl amino acid derivatives, previously studied
electrochemically, were considered in computational study. Some useful DFT parameters, MEP,
EHOMO and ELUMO energies were used to consider charge distribution and electronic density of
investigated compounds in terms of their electrochemical behavior. Obtained results supported
electrochemical findings and indicated on additional redox centers
Comparing overlapping mean response, desirability functions, and analytical quality by design approaches to the optimization of chaotropic chromatography method for the separation of citalopram and its impurities
No full textTradicionalni pristupi multikriterijumskoj optimizaciji, kao što su primena funkcija poželjnih
odgovora i preklapanje prosečnih odgovora, nisu u skladu sa definicijom prostora dizajna datom u ICH Q14,
jer ne pružaju meru osiguranja kvaliteta, tj. verovatnoću da ključni atributi kvaliteta ispunjavaju granične
vrednosti prihvatljivosti [1]. Dodatni problem je što ovi pristupi ne uzimaju u obzir nesigurnost u
procenjenim vrednostima koeficijenata modela, niti korelaciju reziduala regresionih modela [2]. Cilj ovog
rada bio je da se ispita koliko se pomenute teorijske razlike odražavaju na rezultate optimizacije na primeru
metode za ispitivanje stabilnosti citaloprama u tabletama. U ovom slučaju, retencioni factor nečistoće A (k)
i rezolucija između citaloprama i nečistoće E ( Rs) izabrani su kao kritični atributi kvaliteta sa sledećim
graničnim vrednostima: k > 1 i Rs > 2. Kritični parametri analitičke metode bili su sadržaj acetonitrila i
koncentracija perhlorata u mobilnoj fazi i temperatura kolone. Upoređeni su region dobijen preklapanjem
odgovora, region pri kojem je vrednost funkcije poželjnih odgovora veća od 0,6 i prostor dizajna određen
Bajesovom analizom. Na osnovu dvodimenzionalnih grafičkih prikaza utvrđeno je da se optimalni region
dobijen tradicionalnim pristupima u velikoj meri poklapa sa prostorom dizajna. Razlog za to može biti slaba
korelacija reziduala (–0,26) i male standardne greške koeficijenata modela (0,0015–0,0240). S obzirom na
odsustvo komercijalno dostupnih softvera za određivanje prostora dizajna prema ICH Q14, moguća
alternativa je da se prikažu mere nesigurnosti parametara i korelacije reziduala zajedno sa rezultatima
tradicionalne optimizacije, čime se obezbeđuje dodatna garancija kvaliteta analitičke metode.Traditional approaches to multicriteria optimization, including desirability functions and overlapping mean responses (OMRs), are not aligned with definition of design space in ICH Q14 because they do not provide a measure of quality assurance, i.e., the probability that critical quality attributes (CQAs) meet acceptance limits [1]. Furthermore, these approaches neglect uncertainty of the model coefficient estimates and correlation of the regression residuals [2]. The aim of this work was to evaluate how such theoretical differences affect the optimization results using the example of a stability-indicating method for citalopram tablets. In this case, the retention factor of impurity A (k) and the resolution between citalopram and impurity E (Rs) were selected as CQAs with the following acceptance limits: k > 1 and Rs > 2. Critical parameters of the analytical method were acetonitrile content, perchlorate concentration in the mobile phase, and column temperature. The region obtained by OMR, the region where the global desirability function exceeded 0.6, and the design space derived by Bayesian analysis were compared. Two-dimensional contour plots showed that the optimal regions obtained by traditional approaches largely overlapped with the design space. This can be explained by the low correlation of the residuals (−0.26) and the low standard errors of the model coefficients (0.0015–0.0240). Since there is no available software to determine the design space according to ICH Q14, a possible alternative is to report the measures of parameters uncertainty and residual correlation along with traditional optimization results, providing an additional measure of analytical method quality
Markers of cholesterol synthesis and absorption and sphingolipid profile in preeclampsia
No full textUprkos napretku u razjašnjavanju patofizioloških mehanizama uključenih u razvoj preeklampsije,jedina efikasna terapija je porođaj, a rizik za razvoj preeklampsije se najčešće procjenjuje na osnovudemografskih karakteristika i faktora rizika prisutnih kod majke, koji imaju niske pozitivne prediktivnevrijednosti. Kako kardiovaskularne bolesti i preeklampsija dijele niz zajedničkih faktora rizika, aporemećaji u metabolizmu lipida i lipoproteina se smatraju ključnim faktorima u patogeneziateroskleroze i razvoju kardiovaskularnih bolesti, nameće se potreba za detaljnijim ispitivanjempromjena u metabolizmu lipida i njihovog značaja u predikciji rizika za razvoj preeklampsije. Cilj ovogistraživanja bio je longitudinalno praćenje specifičnih komponenti lipidoma kod žena savisokorizičnom trudnoćom, analiza razlika u specifičnim elementima lipidoma između trudnica sa i bezpreeklampsije, i procjena dijagnostičke tačnosti ispitivanih parametara.U studiju je uključeno 90 trudnica sa visokim rizikom sa razvoj preeklampsije, a koje su se javile radipraćenja trudnoće u Ginekološko-akušersku kliniku „Narodni Front“ u Beogradu. Na osnovuprimarnog ishoda trudnoće, ispitanice su klasifikovane u grupu trudnica sa visokorizičnom trudnoćom(RG), koja nije razvila preeklampsiju, i grupu trudnica sa preeklampsijom (PG). U prvoj faziistraživanja određeni su osnovni klinički i biohemijski parametri i osnovni parametri lipidnog profilatokom prvog, drugog, trećeg trimestra i pred porođaj. Koncentracije neholesterolskih sterola (NHS) userumu i lipoproteinskim česticama visoke gustine (HDL) su određene metodama tečne hromatografijesa tandem masenom detekcijom (HPLC-MS/MS), prethodno implementiranim i validiranim ulaboratoriji Katedre za medicinsku biohemiju, a izabrani sfingolipidi HPLC-MS/MS metodomrazvijenom za potrebe ove studije, takođe, u četiri tačke tokom gestacije. Masena koncentracijaapolipoproteina M (apoM) je određivana tehnikom enzimskog imunoeseja. Aktivnosti lecitin-holesterolaciltransferaze (LCAT) i holesterol-estar transfernog proteina (CETP) su procijenjene na osnovu brzinestvaranja i prenosa holesterol estara. Aktivnost paraoksonaze 1 (PON1) mjerena je kinetičkikorišćenjem paraoksona kao supstrata.U okviru studije uspješno je optimizovana i validirana HPLC-MS/MS metoda za kvantifikacijusfingozina, sfinganina, sfingozin-1-fosfata (S1P), sfinganin-1-fosfata, ceramida C16:0 (Cer C16:0) iC24:0 (Cer C24:0), i sfingomijelina C16:0 (SM C16:0). Zbog izraženog efekta matriksa, prilikomkonstrukcije kalibracionih krivih kao matriks je korišten pool humane plazme. Varijacije unutar serijasu bile 3,8-18,8%, a između serija 4,1-19,4%. Tačnost se kretala u opsegu od ± 15% od nominalnevrijednosti. Koncentracije triglicerida su bile značajno više u PG u odnosu na RG (p <0,05 u svimispitivanim tačkama), dok je koncentracija HDL holesterola bila značajno niža u PG u 2. trimestru upoređenju sa RG (p <0,05). Povećanje koncentracije holesterola u RG je bilo praćeno značajnimpovećanjem koncentracija holesterolskih prekursora dezmosterola (p <0,001), 7-dehidroholesterola (p<0,05) i latosterola (p <0,001). S druge strane, u PG uprkos povećanju koncentracije ukupnogholesterola, nisu uočene značajne promjene u koncentracijama dezmosterola (p = 0,427) i 7-dehidroholesterola (p =0,368), već samo u koncentraciji latosterola (p <0,05). Porast koncentracijeholesterolskh prekursora krajem trudnoće u RG bio je praćen značajnim padom koncentracija markeraapsorpcije kampesterola (p <0,05) i β-sitosterola (p <0,05), dok u PG uprkos porastu koncentracijelatosterola nije bilo značajnih promjena u koncentracijama biljnih sterola (p =0,364 za kampesterol i p=0,426 za β-sitosterol), što upućuje na djelimično izmjenjenu homeostazu holesterola u PG. Uočeni surazličiti obrasci u sfingolipidnim profilima između ispitivanih grupa. Koncentracije S1P u RG su sepovećavale od 1. trimestra do porođaja (p <0,001)...Despite advancements in elucidating the pathophysiological mechanisms involved in the developmentof preeclampsia, delivery remains the only effective therapy. The risk of developing preeclampsia ismost commonly assessed based on demographic characteristics and maternal risk factors, which havelow positive predictive values. Since cardiovascular diseases and preeclampsia share numerous riskfactors, and lipid and lipoprotein metabolism disorders are considered key factors in the pathogenesisof atherosclerosis and the development of cardiovascular diseases, there is a need for a more detailedinvestigation of lipid metabolism changes and their significance in predicting the risk of preeclampsia.The aim of this study was to longitudinally monitor specific components of the lipidome in womenwith high-risk pregnancies, analyze differences in specific lipidome elements between women with andwithout preeclampsia, and evaluate the diagnostic accuracy of the examined parameters.The study included 90 pregnant women at high risk for developing preeclampsia, who were monitoredat the Gynecology and Obstetrics Clinic "Narodni Front" in Belgrade. Based on the primary pregnancyoutcome, participants were classified into a high-risk pregnancy group (RG) that did not developpreeclampsia and a preeclampsia group (PG). In the first phase of the study, basic clinical andbiochemical parameters, as well as lipid profile parameters, were determined during the first, second,and third trimesters, and before delivery. Concentrations of non-cholesterol sterols (NCS) in serum andhigh-density lipoprotein particles (HDL) fraction were measured using liquid chromatography-tandemmass spectrometry (HPLC-MS/MS) methods previously implemented and validated in the laboratoryof the Department of Medical Biochemistry. Selected sphingolipids were measured using an HPLCMS/MS method developed specifically for this study, also at four gestational points. The massconcentration of apolipoprotein M (apoM) was determined using an enzyme immunoassay technique.The activities of lecithin-cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein(CETP) were assessed based on the rates of cholesterol ester formation and transfer. Paraoxonase 1(PON1) activity was measured kinetically using paraoxon as a substrate.In this study, an HPLC-MS/MS method was successfully optimized and validated for quantifyingsphingosine, sphinganine, sphingosine-1-phosphate (S1P), sphinganine-1-phosphate, ceramide C16:0(Cer C16:0), ceramide C24:0 (Cer C24:0), and sphingomyelin C16:0 (SM C16:0). Due to a pronouncedmatrix effect, a pool of human plasma was used as the matrix for constructing calibration curves. Intraassayvariations ranged from 3.8% to 18.8%, while inter-assay variations were between 4.1% and19.4%, with accuracy within ±15% of the nominal values. Triglyceride concentrations weresignificantly higher in the PG compared to the RG (p < 0.05 at all points), while HDL cholesterollevels were significantly lower in PG during the 2nd trimester compared to RG (p < 0.05). In RG, anincrease in cholesterol concentrations was accompanied by significant increases in cholesterolprecursors desmosterol (p < 0.001), 7-dehydrocholesterol (p < 0.05), and lathosterol (p < 0.001). In PG,despite rising total cholesterol levels, no significant changes were observed for desmosterol (p = 0.427)or 7-dehydrocholesterol (p = 0.368), with only lathosterol showing a significant increase (p < 0.05).Late pregnancy increases in cholesterol precursors in RG were associated with significant decreases inabsorption markers campesterol (p < 0.05) and β-sitosterol (p < 0.05). In contrast, PG showed nosignificant changes in phytosterols’ concentrations despite lathosterol increases (p = 0.364 forcampesterol and p = 0.426 for β-sitosterol), indicating altered cholesterol homeostasis in PG. Distinctsphingolipid profiles were observed between the groups. S1P concentrations in RG increased from the1st trimester to delivery (p < 0.001)..
Comprehensive Phytochemical Analysis and Evaluation of Antioxidant, Antimicrobial, Cytotoxic, and Immunomodulatory Activities of Commercial Cinnamon Bark Essential Oil (Cinnamomum zeylanicum L.)
No full textThe essential oil derived from the bark of Cinnamomum zeylanicum L., Lauraceae, has gained significant attention because of its numerous biological benefits. This study aimed to perform a phytochemical analysis of commercially available Cinnamomum zeylanicum bark essential oil and to evaluate its antioxidant, antimicrobial, immunomodulatory, and antitumor properties. GC–MS analysis was employed to determine the phytochemical composition. The major component of the total essential oil composition was (E)-cinnamaldehyde, constituting 77.93%, followed by eugenol (4.34%), E-caryophyllene (3.68%), and linalool (2.79%). The antioxidant activity was confirmed by DPPH, ABTS, CUPRAC, and TAC assays. In the broth microdilution assay, cinnamon essential oil demonstrated strong antimicrobial activity, with MIC values ranging from 7.37 to 29.50 µg/mL. Furthermore, cinnamon essential oil demonstrated selective antitumor activity by inducing apoptosis and cell-cycle arrest in human colorectal cancer cells (HCT116) while sparing non-cancerous cells (MRC-5). In HCT116 cells, cinnamon essential oil induced apoptosis, downregulated Cyclin D and p-AKT, and caused G1-phase arrest. Additionally, cinnamon essential oil modulated immune responses by reducing pro-inflammatory cytokine production in activated splenocytes and enhancing pro-inflammatory activity in naïve cells. These findings highlight the great potential of the cinnamon bark essential oil in the development of new therapeutic agents
Antioxidant, Enzyme-Inhibitory and Antimicrobial Activity of Underutilized Wheat and Maize Crop Residues
No full textGlobal wheat and maize production, which reached two billion tonnes in 2021, generates significant agricultural waste with largely untapped potential. This study investigates the bioactive properties of ethanol extracts from wheat and maize harvest residues, their ethyl acetate fractions, and their principal compounds. In vitro assays (DPPH, ABTS, FRAP, and TRC) revealed variable antioxidant capacities among the samples, with ferulic acid demonstrating the strongest free-radical scavenging and reducing effects, often surpassing those of standard antioxidant controls. Enzyme inhibition assays identified the flavonoid tricin as the most effective inhibitor of α-glucosidase, acetylcholinesterase, and butyrylcholinesterase, while the flavonolignan mixture of salcolins A and B showed the highest inhibitory activity against α-amylase and tyrosinase. Antimicrobial testing using the broth microdilution method resulted in minimum inhibitory concentrations (MICs) ranging from 31.25 µg/mL to >1000 µg/mL. Gram-positive bacteria showed the highest susceptibility, Candida albicans exhibited variable sensitivity, and Gram-negative bacteria were resistant in the tested concentration range. Bioactivity increased in the order of extracts, fractions, and then individual compounds. These findings suggest that wheat and maize residues possess notable bioactive properties, highlighting their potential as sources of valuable and pharmacologically active compounds
Development and robust optimization of the RP-HPLC method for the determination of riociguat and its four impurities in tablets using the AQbD approach
No full textThe aim of this work was to develop and optimize the RP-HPLC method for the qualitative and quantitative analysis of riociguat and its four impurities using the Analytical Quality by Design concept. Risk assessment was carried out as a combination of Ishikawa diagram - Control, Noise and eXperimental - Failure mode and effect analysis from where critical method parameters for this study were selected (i.e. acetonitrile content in the mobile phase, concentration of ammonium acetate in aqueous part of mobile phase and column temperature). Their effects on critical method attributes (retention factor of the last eluting peak and separation of critical peak pairs) were further analyzed using the Design of Experiments methodology. The Design Space was defined as the area in which the robustness of the qualitative performance of the developed method is confirmed. Monte Carlo simulations were applied to achieve the defined quality by propagating the error resulting from the calculated coefficients of the mathematical models. The optimal chromatographic conditions included separation on an Xterra® RP18 (150 × 4.6 mm, 3.5 µm) column with a mobile phase consisting of 34 % of acetonitrile and 66 % of aqueous 15 mM ammonium acetate solution pH 5.5, at a column temperature of 36°C. The flow rate was 1 mL/min, the detection wavelength was 210 nm, while the injection volume was 20 µL. Validation of the developed method was performed, which confirmed its reliability in determining the content of riociguat and its four impurities in tablets
Donut-shaped [NaP5W30O110]14− polyoxometalate as a promising antidiabetic drug-candidate: putative mechanisms of action
No full textThe aim of this study was to elucidate the potential mechanism of the antihyperglycemic action of the donut-shaped Preyssler-Pope-Jeannin polyanion salt (NH4)14[NaP5W30O110] 31H2O (NaP5W30) and its effect on metabolic disorders associated with diabetes. For this purpose, relevant parameters of blood glucose regulation, lipid profile, and electrolyte status were monitored in streptozotocin (STZ)-induced diabetic rats that were orally treated with 20 mg/kg/day NaP5W30 for three weeks. The serum insulin concentration was increased in diabetic animals treated with NaP5W30 (20 mg/kg/day, per os, three weeks), which could be one of the possible mechanisms of the confirmed antihyperglycemic effect. In addition, the administration of NaP5W30 significantly reduced hyperglycemia and glycated haemoglobin A1c (HbA1c) in STZ-induced diabetic rats, although normoglycemic values were not achieved. Furthermore, a statistically significant 1.3-fold reduction in serum total cholesterol and a 1.7-fold reduction in high-density lipoprotein (HDL) cholesterol were observed in the NaP5W30 treatment group compared to the diabetic control group. In contrast, NaP5W30 had no effect on homeostasis model assessment of insulin resistance (HOMA-IR) index values, electrolyte concentrations, or serum concentrations of low-density lipoprotein (LDL) cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), or total triglycerides. In summary, NaP5W30 effectively improved glycoregulation in diabetic rats via the considerable stimulation of insulin as a putative mechanism. Moreover, NaP5W30 did not affect rat weight or disrupt lipid and electrolyte status, common diabetes-followed side effects and risk factors for various life-threatening complications. Thus, NaP5W30 could be considered a promising antidiabetic drug-candidate that deserves further investigation
Topical drug formulation for enhanced permeation: A comparison of Bayesian optimisation and response surface methodology with an ibuprofen-loaded poloxamer 407-based formulations case study
No full textTopical skin products aim to address aesthetic, protective, and/or therapeutic needs through interaction with the human epidermal system. Traditionally, formulation development relies on empirical knowledge and trial-and-error experiments. In this paper, we introduced the Bayesian optimisation method and compared it with the traditional response surface methodology (RSM) for topical drug formulation. The objective was to optimise the formulation composition of ibuprofen gel-like to achieve a maximum flux through in vitro permeation tests (IVPTs). As a model system, poloxamer 407, ethanol, and propylene glycol (PG) were selected as the key excipients, whose concentrations were optimised. Strat-M membrane, serving as a surrogate for human skin, and Franz cell diffusion were employed in IVPTs. Two sets of experiments were conducted under identical conditions for 30 h. Under the RSM approach, the optimised ibuprofen gel-like formulation was identified with a poloxamer 407: ethanol: PG ratio of 20:20:10, achieving a measured permeation flux of 11.28 ± 0.35 μg cm−2h−1. In comparison, Bayesian optimisation, after four iterations, yielded an optimised formulation with a ratio of 20.95:19.44:12.14, resulting in a permeation flux of 14.15 ± 0.77 μg cm−2h−1. These findings highlight the potential of Bayesian optimisation as an effective tool for improving topical drug formulations
Unraveling sphingolipid dynamics in late-onset preeclampsia: Insights from lipidomic analysis
No full textIntroduction: Sphingolipids, essential to trophoblast and endothelial function, may impact inflammation in preeclampsia. However, their specific role in late-onset preeclampsia remains unclear. To address this research gap, we analyzed sphingolipid profiles in pregnancies at high risk for preeclampsia development to identify potential biomarkers and clarify their role in disease pathogenesis. Materials and methods: We monitored 90 pregnant women at high risk for preeclampsia development across four gestational points. These women were later categorized into the group of women with high risk who did not develop preeclampsia (HRG) (70 women) or the preeclampsia group (PG) (20 women). Sphingolipids (sphingosine, sphinganine, sphingosine-1-phosphate (S1P), ceramides C16:0/C24:0, and sphingomyelin C16:0) were quantified via liquid chromatography-tandem mass spectrometry. Results: Sphingolipid profiles revealed distinct patterns between groups. Concentrations of S1P in the HRG increased from the 1st trimester to delivery (P < 0.001). We did not notice significant changes in S1P during pregnancy in the PG but compared with the HRG we found significantly lower concentrations at each test point from the 2nd trimester until delivery (P = 0.020, P = 0.013, P = 0.011, respectively). Ceramides C16:0 and C24:0 demonstrated significant increases over time in HRG (P < 0.001, both). Sphingomyelin C16:0 increased significantly across pregnancy in both groups (P < 0.001 in HRG and P = 0.006 in PG), with no significant differences between groups. Conclusions: We identified S1P as a potential biomarker for late-onset preeclampsia, with lower concentrations observed in PG compared to HRG. Rising sphingomyelin concentrations in both cohorts might serve as a relevant cardiovascular risk indicator in pregnancies at high risk for preeclampsia