scholarly journals The Effects of Prunus spinosa L. Flower Extracts, Model Polyphenols and Phenolic Metabolites on Oxidative/Nitrative Modifications of Human Plasma Components with Particular Emphasis on Fibrinogen In Vitro

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 581
Author(s):  
Anna Marchelak ◽  
Joanna Kolodziejczyk-Czepas ◽  
Paulina Wasielewska ◽  
Pawel Nowak ◽  
Monika A. Olszewska
Keyword(s):  
Molecular Weight ◽  
Human Plasma ◽  
Structural Changes ◽  
Circulatory System ◽  
Thiobarbituric Acid ◽  
Protective Effects ◽  
Phenolic Metabolites ◽  
Prunus Spinosa

Oxidative post-translational modifications of fibrinogen (a multifunctional blood plasma protein essential for hemostasis) are associated with the pathogenesis of cardiovascular disorders (CVDs). Prunus spinosa flower is a herbal medicine used in an adjuvant treatment of CVDs and rich in polyphenolic antioxidants. In the present study, phytochemically standardized P. spinosa flower extracts, their primary native polyphenols and potential phenolic metabolites were evaluated in vitro for their protective effects on fibrinogen (isolated and in the human plasma matrix) using a panel of complementary methods (SDS-PAGE, western blot, C-ELISA, fluorometry, FRAP, TBARS). The results revealed that the tested analytes at in vivo relevant levels (1–5 µg/mL) considerably reduced the structural changes in the fibrinogen molecule under the oxidative stress conditions induced by peroxynitrite. In particular, they diminished the oxidation and/or nitration of amino acid residues, including tyrosine and tryptophan, as well as the formation of high molecular weight aggregates. The decrease in the levels of 3-nitrotyrosine was about 13.5–33.0% and 58.3–97.1% at 1 µg/mL and 50 µg/mL, respectively. The study indicated that low molecular weight polyphenols were crucial for the protective activity of the extracts toward fibrinogen and other human plasma components. The investigated model compounds effectively protected total plasma proteins and lipids against oxidative damage (by reducing the levels of 3-nitrotyrosine and thiobarbituric acid-reactive substances and normalizing/enhancing the non-enzymatic antioxidant capacity of plasma). The work provides insight into the role of native and metabolized polyphenols as contributory factors to the systemic activity of blackthorn flower extracts within the circulatory system.

scholarly journals The Effect of Standardised Flower Extracts of Sorbus aucuparia L. on Proinflammatory Enzymes, Multiple Oxidants, and Oxidative/Nitrative Damage of Human Plasma Components In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Monika A. Olszewska ◽  
Joanna Kolodziejczyk-Czepas ◽  
Magdalena Rutkowska ◽  
Anna Magiera ◽  
Piotr Michel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Human Plasma ◽  
Negative Impact ◽  
Thiobarbituric Acid ◽  
Dry Weight ◽  
Lipid Hydroperoxides ◽  
Sorbus Aucuparia ◽  
Inflammatory Changes

Polyphenol-rich plant extracts might alleviate the negative impact of oxidative stress and inflammation, but careful phytochemical standardisation and evaluation of various mechanisms are required to fully understand their effects. In this context, flower extracts of Sorbus aucuparia L.—a traditional medicinal plant—were investigated in the present work. The LC-MS/MS profiling of the extracts, obtained by fractionated extraction, led to the identification of 66 constituents, mostly flavonols (quercetin and sexangularetin glycosides with dominating isoquercitrin), pseudodepsides of quinic and shikimic acids (prevailing isomers of chlorogenic acid and cynarin), and flavanols (catechins and proanthocyanidins). Minor extract components of possible chemotaxonomic value were flavalignans (cinchonain I isomers) and phenylamides (spermidine derivatives). As assessed by HPLC-PDA and UV-spectrophotometric studies, the extracts were polyphenol-abundant, with the contents up to 597.6 mg/g dry weight (dw), 333.9 mg/g dw, 382.0 mg/g dw, and 169.0 mg/g dw of total phenolics, flavonoids, proanthocyanidins, and caffeoylquinic acids, respectively. Their biological in vitro effects were phenolic-dependent and the strongest for diethyl ether, ethyl acetate, and n-butanol fractions of the methanol-water (7 : 3, v/v) extract. The extracts showed significant, concentration-dependent ability to scavenge in vivo-relevant radical/oxidant agents (O2∙−, OH∙, H2O2, ONOO–, NO∙, and HClO) with the strongest effects towards OH∙, ONOO–, HClO, and O2∙− (compared to ascorbic acid). Moreover, the extracts efficiently inhibited lipoxygenase and hyaluronidase (compared to indomethacin) but were inactive towards xanthine oxidase. At in vivo-relevant levels (1-5 μg/mL), they also effectively protected human plasma components (proteins and lipids) against ONOO–-induced oxidative damage (reduced the levels of 3-nitrotyrosine, lipid hydroperoxides, and thiobarbituric acid-reactive substances) and normalised/enhanced the total nonenzymatic antioxidant capacity of plasma. In cytotoxicity tests, the extracts did not affect the viability of human PBMCs and might be regarded as safe. The results support the application of the extracts in the treatment of oxidative stress-related pathologies cross-linked with inflammatory changes.

scholarly journals High Molecular Weight Hyaluronan Suppresses Macrophage M1 Polarization and Enhances IL-10 Production in PM2.5-Induced Lung Inflammation

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1766 ◽  
Author(s):  
Qiwen Shi ◽  
Lan Zhao ◽  
Chenming Xu ◽  
Leifang Zhang ◽  
Hang Zhao
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Lung Inflammation ◽  
Macrophage Polarization ◽  
Pulmonary Inflammation ◽  
In Vivo Studies ◽  
Protective Effects ◽  
M1 Polarization

PM2.5 is particulate matter with a diameter of 2.5 μm or less. Airway macrophages are the key players regulating PM2.5-induced inflammation. High molecular weight hyaluronan (HMW-HA) has previously been shown to exert protective effects on PM2.5-induced acute lung injury and inflammation. However, little is known about the detailed mechanism. In this study, we aimed to determine whether HMW-HA alleviates PM2.5-induced pulmonary inflammation by modulating macrophage polarization. The levels of M1 biomarkers TNF-α, IL-1β, IL-6, CXCL1, CXCL2, NOS2 and CD86, as well as M2 biomarkers IL-10, MRC1, and Arg-1 produced by macrophages were measured by ELISA, qPCR, and flow cytometry. In addition, the amount of M1 macrophages in lung tissues was examined by immunofluorescence of CD68 and NOS2. We observed a decline in PM2.5-induced M1 polarization both in macrophages and lung tissues when HMW-HA was administered simultaneously. Meanwhile, western blot analysis revealed that PM2.5-induced JNK and p38 phosphorylation was suppressed by HMW-HA. Furthermore, in vitro and in vivo studies showed that co-stimulation with HMW-HA and PM2.5 promoted the expression and release of IL-10, but exhibited limited effects on the transcription of MRC1 and ARG1. In conclusion, our results demonstrated that HMW-HA ameliorates PM2.5-induced lung inflammation by repressing M1 polarization through JNK and p38 pathways and promoting the production of pro-resolving cytokine IL-10.

Comparative Study of the Activity of High and Low Molecular Weight Urokinase in the Presence of Fibrin

1982 ◽  
Vol 47 (01) ◽  
pp. 036-040 ◽  
Author(s):  
M Samama ◽  
M Castel ◽  
O Matsuo ◽  
M Hoylaerts ◽  
H R Lijnen
Keyword(s):  
Molecular Weight ◽  
Human Plasma ◽  
Test System ◽  
Clot Lysis ◽  
Low Molecular Weight ◽  
Plate Method ◽  
Thrombolytic Activity ◽  
Fibrin Plate

SummaryThe fibrinolytic or thrombolytic activity of low molecular weight urokinase (LMW-UK) and high molecular weight urokinase (HMW-UK) is not significantly different when measured in a bovine fibrin plate method, in a circulating plasma system containing a 125I-labelled human fibrin clot, or on 125I-fibrin films in culture plates using normal or α2-antiplasmin depleted human plasma.In a human fibrin plate method however HMW-UK was found to be more active than LMW-UK. In a purified system on human 125I-fibrin films the activation of native or modified human plasminogen by HMW-UK was also found to be more effective than by LMW-UK.Using a clot lysis test system we did not observe a different inhibition of LMW-UK and HMW-UK upon incubation in human plasma. This is in contrast with previous reports that HMW-UK is inhibited more rapidly in human plasma than LMW-UK.In a purified system the inhibition rate of LMW-UK and HMW-UK by α2-antiplasmin is the same (rate constants at 25ΰC of 167 ± 9 M−1s−1 and 171 ± 5 M−1s−1 respectively).The clinical trials available at present used doses of urokinase which were in excess of those required to obtain a maximal fibrinolytic effect. This might explain why in these trials no difference was observed between the thrombolytic effect of LMW-UK and HMW-UK, while in vitro HMW-UK appeared to be more effective. However, one should always be careful to extrapolate in vitro observations as such to the in vivo situation encountered during thrombolytic therapy.

scholarly journals Bioactivity Potential of Aesculus hippocastanum L. Flower: Phytochemical Profile, Antiradical Capacity and Protective Effects on Human Plasma Components under Oxidative/Nitrative Stress In Vitro

2021 ◽  
Vol 14 (12) ◽  
pp. 1301
Author(s):  
Aleksandra Owczarek ◽  
Joanna Kołodziejczyk-Czepas ◽  
Paulina Marczuk ◽  
Julia Siwek ◽  
Katarzyna Wąsowicz ◽  
...  
Keyword(s):  
Human Plasma ◽  
Thiobarbituric Acid ◽  
Aesculus Hippocastanum ◽  
Horse Chestnut ◽  
Protective Effects ◽  
Total Polyphenol ◽  
Nitrative Stress ◽  
Kaempferol Glycosides ◽  
First Time

Horse chestnut (Aesculus hippocastanum) flower is a traditional medicine applied to alleviate symptoms of chronic venous insufficiency (CVI). However, its flavonoid-based composition has not been sufficiently recognized, and the data supporting its traditional application are lacking. In the work, 43 constituents were detected by UHPLC–PDA–ESI–TQ–MS/MS (flavonoids, phenolic acids, flavanols, and coumarins), including 31 reported in the flower for the first time. The quantitative HPLC–PDA study (developed and validated for quality control purposes) indicated the fractionated extraction as an efficient method for enhancing the total polyphenol content (TPHC) in the extracts (up to 414.06 mg/g) and kaempferol glycosides as their dominant constituents (75.05–82.14% TPHC). The activity studies showed significant scavenging properties of the extracts and their constituents towards reactive oxygen species (especially against highly reactive hydroxyl radical, with capacities up to 7.85 mmol ascorbic acid equivalents/g). Moreover, the analytes relevantly protected human plasma biomolecules from peroxynitrite-induced oxidative/nitrative damage; at 1–50 µg/mL, they hindered the protein nitration and lipid peroxidation, decreasing the levels of 3-nitrotyrosine (by up to 50%) and thiobarbituric acid reactive substances (by up to 70%), respectively. The extracts also averted the depletion of plasma thiols (by up to 67%) and improved the non-enzymatic antioxidant capacity of plasma. The demonstrated mechanisms might be partly responsible for the efficacy of the flower in CVI. Additionally, the anti-aggregatory and anticoagulant properties of the extracts were found only mild or negligible, which suggests that they may be safely applied with drugs impacting the coagulation process.

scholarly journals Protective Effects of Inflammation of Curcumae Longae Rhizoma 30% EtOH Extract on Acute Reflux Esophagitis Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Jin A. Lee ◽  
Mi-Rae Shin ◽  
Min Ju Kim ◽  
Ji Hye Lee ◽  
Hae-Jin Park ◽  
...  
Keyword(s):  
Reflux Esophagitis ◽  
Stomach Contents ◽  
Thiobarbituric Acid ◽  
Thiobarbituric Acid Reactive Substance ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Related Factors ◽  
Etoh Extract

Gastroesophageal reflux disease (GERD) is induced by the reflux of stomach contents or gastric acid, pepsin into the esophagus for prolonged periods of time due to defection of the lower esophageal sphincter. Reflux esophagitis is a disease found in less than 50% of GERD patients. This study is aimed at evaluating the protective effect of Curcumae longae Rhizoma 30% EtOH extract (CLR) in acute reflux esophagitis (ARE) rats. CLR measured antioxidant activity through in vitro experiments. Based on the results, we performed experiments in vivo. Before 90 min ARE induction, CLR was administered orally by concentration. ARE was derived by linking the metastatic junction between pylorus and forestomach and corpus in Sprague-Dawley rats. And rats were sacrificed 5 h after surgery. We analyzed the expression of antioxidant and inflammatory-related markers by western blot and observed the production of alanine aminotransferase (ALT), aspartate aminotransferase (AST), reactive oxygen species (ROS), peroxynitrite (ONOO-), and thiobarbituric acid reactive substance (TBARS). The administration of CLR reduced esophagus tissue damage in rats with acute reflux esophagitis and decreased the elevated ALT, AST, ROS, ONOO-, and TBARS. In addition, CLR effectively increased antioxidant-related factors and reduced inflammatory protein. Overall, these results suggest that CLR would be used as a therapeutic material in protection and treatment for ARE. Overall, CLR treatment informed that markedly ameliorated inactivation of NF-κB led to the inhibition of the expressions of proinflammatory proteins. These results suggest that CLR would be used as a therapeutic material in protection and treatment for ARE.

Potentially Thrombogenic Materials in Factor IX Concentrates

1975 ◽  
Vol 33 (03) ◽  
pp. 617-631 ◽  
Author(s):  
H. S Kingdon ◽  
R. L Lundblad ◽  
J. J Veltkamp ◽  
D. L Aronson
Keyword(s):  
Human Plasma ◽  
Antithrombin Iii ◽  
Factor Ix ◽  
In Vitro Assays ◽  
Substantial Agreement ◽  
Coefficient Of Correlation

SummaryFactor IX concentrates manufactured from human plasma and intended for therapeutic infusion in man have been suspected for some time of being potentially thrombogenic. In the current studies, assays were carried out in vitro and in vivo for potentially thrombogenic materials. It was possible to rank the various materials tested according to the amount of thrombogenic material detected. For concentrates not containing heparin, there was substantial agreement between the in vivo and in vitro assays, with a coefficient of correlation of 0.77. There was no correlation between the assays for thrombogenicity and the antithrombin III content. We conclude that many presently available concentrates of Factor IX contain substantial amounts of potentially thrombogenic enzymes, and that this fact must be considered in arriving at the decision whether or not to use them therapeutically.

Presence and Possible Origin of ɛ(γ-Glutamyl)Lysine Isodipeptide in Human Plasma

1992 ◽  
Vol 67 (01) ◽  
pp. 060-062 ◽  
Author(s):  
J Harsfalvi ◽  
E Tarcsa ◽  
M Udvardy ◽  
G Zajka ◽  
T Szarvas ◽  
...  
Keyword(s):  
Human Plasma ◽  
Fibrinolytic Therapy ◽  
Normal Human Plasma ◽  
Normal Human ◽  
Hplc Technique ◽  
Significant Change

Summaryɛ(γ-glutamyl)lysine isodipeptide has been detected in normal human plasma by a sensitive HPLC technique in a concentration of 1.9-3.6 μmol/1. Incubation of in vitro clotted plasma at 37° C for 12 h resulted in an increased amount of isodipeptide, and there was no further significant change when streptokinase was also present. Increased in vivo isodipeptide concentrations were also observed in hypercoagulable states and during fibrinolytic therapy.

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

Toxicity of Heparinoids, with Special Reference to the Precipitation of Fibrinogen

1964 ◽  
Vol 12 (01) ◽  
pp. 232-261 ◽  
Author(s):  
S Sasaki ◽  
T Takemoto ◽  
S Oka
Keyword(s):  
Molecular Weight ◽  
Dextran Sulfate ◽  
Anticoagulant Activity ◽  
Molecular Structures ◽  
Severe Reaction ◽  
Clinical Use ◽  
Molecular Weights ◽  
Close Relationship

SummaryTo demonstrate whether the intravascular precipitation of fibrinogen is responsible for the toxicity of heparinoid, the relation between the toxicity of heparinoid in vivo and the precipitation of fibrinogen in vitro was investigated, using dextran sulfate of various molecular weights and various heparinoids.1. There are close relationships between the molecular weight of dextran sulfate, its toxicity, and the quantity of fibrinogen precipitated.2. The close relationship between the toxicity and the precipitation of fibrinogen found for dextran sulfate holds good for other heparinoids regardless of their molecular structures.3. Histological findings suggest strongly that the pathological changes produced with dextran sulfate are caused primarily by the intravascular precipitates with occlusion of the capillaries.From these facts, it is concluded that the precipitates of fibrinogen with heparinoid may be the cause or at least the major cause of the toxicity of heparinoid.4. The most suitable molecular weight of dextran sulfate for clinical use was found to be 5,300 ~ 6,700, from the maximum value of the product (LD50 · Anticoagulant activity). This product (LD50 · Anticoagulant activity) can be employed generally to assess the comparative merits of various heparinoids.5. Clinical use of the dextran sulfate prepared on this basis gave satisfactory results. No severe reaction was observed. However, two delayed reactions, alopecia and thrombocytopenia, were observed. These two reactions seem to come from the cause other than intravascular precipitation.

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