scholarly journals Anticoagulant Activity of Polyphenolic-Polysaccharides Isolated fromMelastoma malabathricumL.

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Li Teng Khoo ◽  
Faridah Abas ◽  
Janna Ong Abdullah ◽  
Eusni Rahayu Mohd Tohit ◽  
Muhajir Hamid
Keyword(s):  
Solid Phase ◽  
Chemical Constituents ◽  
Anticoagulant Activity ◽  
Hot Water ◽  
Neutral Sugar ◽  
Dependent Manner ◽  
Asian Countries ◽  
Melastoma Malabathricum ◽  
Solid Phase Extraction Cartridge ◽  
Dose Dependent

Melastoma malabathricumLinn. is a perennial traditional medicine plants that grows abundantly throughout Asian countries. In this study,M. malabathricumLinn. leaf hot water crude extract with anticoagulant activity was purified through solid phase extraction cartridge and examined for the bioactive chemical constituents on blood coagulation reaction. The SPE purified fractions were, respectively, designated as F1, F2, F3, and F4, and each was subjected to the activated partial thromboplastin time (APTT) anticoagulant assay. Active anticoagulant fractions (F1, F2, and F3) were subjected to chemical characterisation evaluation. Besides, neutral sugar for carbohydrate part was also examined. F1, F2, and F3 were found to significantly prolong the anticoagulant activities in the following order,F1>F2>F3, in a dose dependent manner. In addition, carbohydrate, hexuronic acid, and polyphenolic moiety were measured for the active anticoagulant fractions (F1, F2, and F3). The characterisation of chemical constituents revealed that all these three fractions contained acidic polysaccharides (rhamnogalacturonan, homogalacturonan, and rhamnose hexose-pectic type polysaccharide) and polyphenolics. Hence, it was concluded that the presence of high hexuronic acids and polysaccharides, as well as polyphenolics in traditional medicinal plant,M. malabathricum, played a role in prolonging blood clotting in the intrinsic pathway.

Reversal of Dabigatran's Anticoagulant Activity in the Monkey by a Specific Antidote and Pharmacokinetic and Pharmacodynamic Modeling

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 22-22 ◽  
Author(s):  
Joshuaine Toth ◽  
Guanfa Gan ◽  
Joanne van Ryn ◽  
Holly Dursema ◽  
Jennifer Isler ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Anticoagulant Activity ◽  
Plasma Concentrations ◽  
Mass Action ◽  
Pharmacodynamic Modeling ◽  
Dependent Manner ◽  
Thrombin Time ◽  
Binding Interaction ◽  
Mass Action Kinetics ◽  
Dose Dependent

Abstract Abstract 22 Background: The objective of this study is to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of dabigatran (a small molecule thrombin inhibitor) and its antidote (a humanized Fab against dabigatran) in the monkey and to develop a combined mechanistic mathematical model to describe the data. Methods: There were three groups: control, antidote alone and dabigatran etexilate (DE) + antidote. Rhesus monkeys (n = 2/group) received either 12 mg/kg/day of DE or vehicle orally on Days 1–4, 15–18 and 29–32 with a single IV dose of the antidote administered 90 minutes after DE on Days 4, 18 and 32. Doses of the antidote were 30, 90 or 175 mg/kg, respectively. PK parameters of the antidote and sum dabigatran (dabigatran plus its glucuronides) were determined after measurements of plasma concentrations. Coagulation activity was measured using a diluted thrombin time assay to determine the activity of the unbound sum dabigatran. Results: The PK of the antidote were not affected by dabigatran. Clearance of the antidote was low (0.87 mL/min/kg) and steady-state volume of distribution was small (0.06 L/kg), indicating that the antidote was mostly restricted to plasma. The plasma profile of the antidote was bi-phasic with a short initial phase t1/2 of 0.4 hour (h) and a terminal phase t1/2 of 4.3 h. Immediately after antidote dosing, plasma concentrations of sum dabigatran increased, a consequence of the rapid redistribution of dabigatran and its glucuronides from tissue to plasma due to binding to the antidote. Complete reversal of dabigatran's anticoagulant activity was observed immediately after antidote dosing at all three dose levels, as measured by the diluted thrombin time assay, which indicates that all dabigatran was bound to the antidote. The degree to which this reversal effect was maintained over an extended period (24 h) was dose-dependent. A mechanistic ordinary differential equation model, based on the mass action kinetics for describing the distribution, binding and elimination of dabigatran and its antidote, was developed by combining the PK models for dabigatran and the antidote and adding the binding interaction (1:1 stoichiometry) between the two compounds. The distribution and elimination parameters of the dabigatran-antidote complex were assumed to be the same as those of the antidote, based on similar measured PK parameters of the antidote with and without dabigatran in the monkey. The combined PK/PD model of dabigatran and antidote was able to describe the in vivo PK/PD data observed in monkeys. Conclusion: The dabigatran-specific antidote successfully reversed the anticoagulant activity of dabigatran in the monkey in a dose-dependent manner, and our combined mathematical model accurately describes monkey PK/PD data of sum dabigatran and its antidote. Insights gained from this model will be used to guide model development for clinical trials. Disclosures: Toth: Boehringer Ingelheim: Employment. Gan:Boehringer Ingelheim: Employment. van Ryn:Boehringer Ingelheim: Employment. Dursema:Boehringer Ingelheim: Employment. Isler:Boehringer Ingelheim: Employment. Coble:Boehringer Ingelheim: Employment. Burke:Boehringer Ingelheim: Employment. Lalovic:Boehringer Ingelheim: Employment. Olson:Boehringer Ingelheim: Employment.

scholarly journals Melanogenesis inhibitory activity of Korean Undaria pinnatifida in mouse B16 melanoma cells

2014 ◽  
Vol 7 (2) ◽  
pp. 89-92 ◽  
Author(s):  
Min-Jin Kim ◽  
Dong Sam Kim ◽  
Hun-Seok Yoon ◽  
Wook Jae Lee ◽  
Nam Ho Lee ◽  
...  
Keyword(s):  
Undaria Pinnatifida ◽  
Traditional Food ◽  
Dependent Manner ◽  
Asian Countries ◽  
Melanin Content ◽  
Traditional Foods ◽  
Whitening Agent ◽  
Few Data ◽  
Dose Dependent ◽  
Different Parts

ABSTRACT A number of seaweed species are used as traditional foods and medicine in different parts of the world, including Asian countries. However, very few data on the anti-melanogenic effect of seaweed have been published. Undaria pinnatifida (Dolmiyeok), a brown alga, is a traditional food in Jeju Island, the southern regions of the Korea peninsula. In this study, ethylacetate extracts of U. pinnatifida (UPE) were examined for their anti-melanogenic potentials. Our results supports the finding that UPE down-regulated melanin content in a dose-dependent pattern. To clarify the target of UPE action in melanogenesis, we performed Western blotting for tyrosinase and microphthalmia-associated transcription factor (MITF), which are key melanogenic enzymes. UPE inhibited tyrosinase and MITF expressions in a dose-dependent manner. These results indicate that treatment with UPE significantly inhibits the melanogenesis in B16 cells, and may be effective in the whitening agent for the skin

scholarly journals INVESTIGATION ON PHARMACOGNOSY AS WELL AS THE ANTIOXIDANT, ANTI-INFLAMMATORY POTENTIAL OF THE KATHA POWDER

2021 ◽  
pp. 125-132
Author(s):  
PANKAJ SHARMA ◽  
RAJU L
Keyword(s):  
Diclofenac Sodium ◽  
In Vitro Study ◽  
Alcoholic Solution ◽  
Hot Water ◽  
Dependent Manner ◽  
Standard Drug ◽  
Anti Inflammatory ◽  
Acacia Catechu ◽  
Dose Dependent

Objective: The objective of the study was to investigate the pharmacognosy as well as the antioxidant, anti-inflammatory potential of the Katha powder. Methods: The Coarsely dried chips of Acacia catechu heartwood were treated with 10 % hydro-alcoholic solution to obtain Katha as the final product. The powdered Katha was standardized through pharmacognostic parameters. This Katha power is showing the good solubility in the hot water having astringent in the taste. The powder microscopy of the Katha powder is to be demonstrated fragments of acicular crystals, fibers, and bordered pitted vessels. Katha powder antioxidant potential is to be accessed by using the 2, 2-diphenyl-1-picryl hydrazyl assay and NO Scavenging assay using ascorbic acid as a standard drug. Further, the Katha powder is to be subjected for the assessment of its anti-inflammatory potential by the use of heat-induced hemolysis as well as hypotonicity-induced hemolysis approach by the use of the aspirin or diclofenac sodium as a standard drug. Results: Microscopical investigations were showed that Katha showing the presence of fragments of acicular crystals, fibers, and bordered pitted vessels. In vitro study shows that the Katha powder has excellent antioxidant as well as anti-inflammatory potential in a dose-dependent manner in comparison of the result of heartwood of A. catechu. Conclusion: So from this investigation, it is to be suggested that the Katha powder is rich in the phenolic compound and the experimentation study shows that the drug is to possess a good antioxidant as well as anti-inflammatory property.

Prevention and Therapy of Experimental Venous Thrombosis in Rabbits by Desmin 370

1998 ◽  
Vol 80 (08) ◽  
pp. 338-341 ◽  
Author(s):  
Maria Rosaria Rossiello ◽  
Miriam Barbanti ◽  
Fiorella Calanni ◽  
Nicola Semeraro ◽  
Mario Colucci
Keyword(s):  
Therapeutic Efficacy ◽  
Therapeutic Agent ◽  
Dermatan Sulfate ◽  
Anticoagulant Activity ◽  
Low Molecular Weight ◽  
Dependent Manner ◽  
Jugular Vein Thrombosis ◽  
Vein Thrombosis ◽  
Drug Inhibition ◽  
Dose Dependent

SummaryDesmin 370 (D370), a low molecular weight dermatan sulfate, has been shown to reduce the size of preformed thrombi in rats, via a mechanism largely independent of its anticoagulant activity. In the present study we investigated the therapeutic efficacy of D370 in rabbits with experimental jugular vein thrombosis. Experiments performed to evaluate the antithrombotic dosages in rabbits indicated that D370 prevented the formation of venous thrombi (Wessler model) in a dose-dependent manner with complete inhibition at 20 mg/kg. When injected to rabbits bearing a 30 min aged thrombus, D370 caused a time- and dose-dependent reduction in thrombus weight. Thrombi harvested 2 h after injection of 50 mg/kg of D370 were 71% smaller than thrombi from saline-treated rabbits and 50% smaller than pretreatment thrombi, suggesting a double effect of the drug: inhibition of thrombus accretion and reduction of the existing thrombus. Interestingly, pretreatment with the fibrinolytic inhibitor EACA (1 g/kg), significantly attenuated the therapeutic efficacy of D370, suggesting a possible involvement of the fibrinolytic system. Heparin (50 and 200 U/kg) was less active as therapeutic agent, the maximal decrease in thrombus weight, as compared to untreated rabbits, amounting to 38%. Heparin, moreover, caused a more pronounced prolongation of APTT than comparable antithrombotic dosages of D370. Our present data extend previous results on the therapeutic efficacy of D370 and underscore its potential as an alternative antithrombotic drug.

An IgM Lupus Anticoagulant that Neutralizes the Enhancing Effect of Phospholipid on Purified Endothelial Thrombomodulin Activity-A Mechanism for Thrombosis

1986 ◽  
Vol 55 (03) ◽  
pp. 309-313 ◽  
Author(s):  
J-M Freyssinet ◽  
Marie-Louise Wiesel ◽  
Josiane Gauchy ◽  
B Boneu ◽  
J-P Cazenave
Keyword(s):  
High Performance Liquid Chromatography ◽  
Protein C ◽  
High Performance ◽  
Anticoagulant Activity ◽  
Gel Filtration ◽  
Dependent Manner ◽  
Enhancing Effect ◽  
Lupus Anticoagulants ◽  
Thrombotic Complications ◽  
Dose Dependent

SummaryAn anticoagulant activity was isolated from the plasma of a patient with a strong lupus-like anticoagulant using gel filtration by high performance liquid chromatography. IgM were detected in this anticoagulant fraction which exhibited specificity towards 50% phosphatidylcholine - 50% phosphatidylserine vesicles and cardiolipin. These phospholipids were able to produce an apparent 3-fold enhancement of purified human protein C activation by human a-thrombin in the presence of purified human placenta thrombomodulin. In the absence of phospholipid, the anticoagulant fraction had no effect on thrombomodulin activity. The anticoagulant fraction could neutralize the enhancement of thrombomodulin activity by phospholipid in a dose-dependent manner. This study suggests that the neutralization of phospholipid might result in a reduced activation of protein C which could be responsible for the occurrence of thrombotic complications in a proportion of patients with lupus anticoagulants.

scholarly journals Chemical Constituents of Blumea balsamifera of Indonesia and Their Protein Tyrosine Phosphatase 1B Inhibitory Activity

2012 ◽  
Vol 7 (7) ◽  
pp. 1934578X1200700 ◽  
Author(s):  
Azis Saifudin ◽  
Ken Tanaka ◽  
Shigetoshi Kadota ◽  
Yasuhiro Tezuka
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Inhibitory Activity ◽  
Methanol Extract ◽  
Chemical Constituents ◽  
Tyrosine Phosphatase ◽  
Spectroscopic Methods ◽  
Protein Tyrosine Phosphatase 1B ◽  
Dependent Manner ◽  
Protein Tyrosine ◽  
Dose Dependent

A methanol extract of the leaves of Blumea balsamifera (L.) DC. (Asteraceae) afforded a new guaian-type sesquiterpene, epiblumeaene K (1), together with four known guaian-type sesquiterpenes (2–5), three known sesquiterpenes (6–8), and nine known flavonoids (9–17) by a combination of chromatography and preparative TLC techniques. Their structures were elucidated by extensive spectroscopic methods and comparison with the literature data. Among the isolated compounds, a known sesquiterpene, β-caryophyllene 8 R,9 R-oxide (6), exhibited a significant PTP1B inhibitory activity in a dose-dependent manner, with an IC50 value of 25.8μM (5.62μg/mL).

Effect of heparin and its derivatives on the progression of tumor growth in mouse Lewis lung carcinoma model.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13115-e13115
Author(s):  
Angel Gray ◽  
Debra Hoppensteadt ◽  
Matthew Hejna ◽  
Jawed Fareed
Keyword(s):  
Tumor Growth ◽  
Anticoagulant Activity ◽  
Dose Range ◽  
Saline Control ◽  
Spleen Weight ◽  
Dependent Manner ◽  
Heparin Group ◽  
Prevention Of Cancer ◽  
Cancer Associated Thrombosis ◽  
Dose Dependent

e13115 Background: Preclinical evidence suggests that heparins have an effect on tumor progression independent of their anticoagulant activity. Heparins have also been shown to exhibit interactions with growth factors and other cellular receptors. This study was designed to investigate whether heparin and its derivatives are able to inhibit tumor growth. Methods: Female C57BL/6 mice were obtained at 6-8 weeks of age and were implanted with 5X105 LN7 tumor cells by dorsal subcutaneous injection of in the upper back. When tumors were first palpable, after 7-10 days of growth, mice were treated with subcutaneous injections of heparin, a low molecular weight heparin (LMWH), namely enoxaparin, an ultra LMWH, semuloparin or saline, daily for two weeks in a dose range of 1.0 – 0.25 mg/kg. After the treatment period, animals were sacrificed and the spleens and tumors were removed and their weight, volume, spleen weight and size were measured. Results: At the 1.0 and 0.5 mg/kg dosages, both enoxaparin (p<0.01) and semuloparin (p<0.01) showed a decrease in tumor volume compared to the saline control animals. At the 1.0 mg/kg dosage, the mortality was high in the heparin group due to bleeding. At 0.5 mg/kg heparin was not different from the saline control. In addition, at a dosage of 0.25 mg/kg, only semuloparin showed a difference compared to the saline control (p<0.01). Similar results were observed for the tumor weight. There were no significant differences noted in spleen weight or spleen size among these agents. The mortality rates between the mice treated with enoxaparin and semuloparin were comparable. Conclusions: These studies suggest that heparin and its derivatives are capable of inhibiting tumor growth in a dose dependent manner. Enoxaparin and semuloparin are more effective at reducing tumor growth compared to heparin. Clinical studies have shown that semuloparin is safe and effective for the prevention of venous thromboembolism in cancer patients and compares favorably to enoxaparin in terms of antithrombotic effect and safety profile. Therefore, semuloparin may be a better alternate for the prevention of cancer associated thrombosis.

Identification Of The Thrombin-Binding Site On Factor VIII Regulating Arg372 Cleavage In The Factor VIII Heavy Chain

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3570-3570
Author(s):  
Hiroaki Minami ◽  
Keiji Nogami ◽  
Koji Yada ◽  
Midori Shima
Keyword(s):  
Factor Viii ◽  
Binding Site ◽  
Heavy Chain ◽  
Conflicts Of Interest ◽  
Solid Phase ◽  
Factor Ix ◽  
Cross Linking ◽  
Dependent Manner ◽  
Factor X ◽  
Dose Dependent

Abstract Factor VIII is activated by cleavage at Arg372, Arg740, and Arg1689 by thrombin. Activated factor VIII (VIIIa) forms the tenase complex and markedly amplifies the activation of factor X as a cofactor of factor IX. We had demonstrated that thrombin interacts with factor VIII through the residues 392-394 and 484-509 in the A2 domain and the C2 domain, and each association regulates cleavage at Arg740, Arg372, and Arg1689, respectively (Nogami K, JBC 2000, 2005; BJH 2008). The A2 residues 484-509 partially contribute to cleavage at Arg372 by thrombin, however, the major thrombin binding-site(s) regulating cleavage at Arg372 is unclear. Thrombin recognizes macromolecular substrates and cofactors through either or both of two anion-binding exosite I and II (ABE-I and -II), which are characterized by a high density of solvent-exposed basic residues. ABE-I binds to fibrinogen and hirudin (residues 54-65), whilst ABE-II is primarily characterized as the heparin-binding exosite. The A1 domain of factor VIII also binds to thrombin through the ABE-I (Nogami K. JBC 2005). In this study, we attempted to identify the thrombin-binding region on A1, and focused on the A1 residues 340-350, involving the clustered acidic residues and similar sequences of hirudin (residues 54-65). A synthetic peptide corresponding to the A1 residues 340-350 with sulfated Tyr346 (340-350-S(+)) was prepared to investigate factor VIII interaction with thrombin. Activation of factor VIII (100 nM) by thrombin (0.4 nM) with various concentrations of peptide was evaluated by measurement of factor VIIIa activity in a one-stage clotting assay. A 340-350-S(+) peptide showed a dose-dependent inhibition (by ∼60%) of thrombin-catalyzed activation, and the IC50 was 75 µM. A non-sulfated peptide also showed a modest inhibition by ∼40% (IC50 >400 µM), however. An experiment using thrombin substrate S-2238 demonstrated that P340-350-S(+) did not affect the thrombin activity. The effect of 340-350-S(+) peptide on the thrombin-catalyzed cleavage of heavy chain was further examined by SDS-PAGE/western blotting.The peptide significantly blocked the cleavage at Arg372 in a timed- and dose-dependent manner (IC50; 150 µM), whilst of interest the cleavage at Arg740 was little affected. A non-sulfated peptide also delayed the cleavage at Arg372, with a modest fast cleavage compared to sulfated one. The peptide did not inhibit factor FXa-catalyzed reaction to factor VIII. Direct binding of 340-350-S(+) peptide to thrombin was examined by a surface resonance plasmon (SPR)-based assay and by the zero-length cross-linking reagent EDC. In SPR-based solid phase assay, thrombin bound to immobilized 340-350-S(+) peptide with high affinity (Kd; 1.13 nM). EDC cross-linking fluid phase assay similarly revealed that formation of EDC cross-linking product between the biotinylated 337-350-S(+) peptide and thrombin were observed, and this cross-linking was completely inhibited by non-labeled 340-350-S(+) peptide (IC50; 1.0 µM). Taken together, we demonstrated that the A1 residues 340-350 (NEEAED(sY)DDDL) involving sulfated Tyr346 contained the thrombin binding-site responsible for the proteolytic cleavage at Arg372 in factor VIII. Disclosures: No relevant conflicts of interest to declare.

Anti-nociceptive activity of a few structurally related trimethoxy flavones and possible mechanisms involved

2016 ◽  
Vol 27 (2) ◽  
Author(s):  
Jagan Nadipelly ◽  
Vijaykumar Sayeli ◽  
Parimala Kadhirvelu ◽  
Jaikumar Shanmugasundaram ◽  
Binoy Varghese Cheriyan ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Hot Water ◽  
Dependent Manner ◽  
Tail Immersion ◽  
Dopaminergic Mechanisms ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Definite Role

AbstractThe present study was designed to investigate the anti-nociceptive activity of a few structurally related trimethoxy flavones (7,2′,3′-TMF, 7,2′,4′-TMF, 7,3′,4′-TMF and 7,5,4′-TMF) and the possible mechanisms involved.Anti-nociceptive activity was evaluated in mice by employing acetic acid-induced writhing, formalin-induced nociception and hot water tail immersion methods. The involvement of opioid, GABAergic, tryptaminergic, adrenergic and dopaminergic mechanisms and KTrimethoxy flavones exhibited a significant and dose-dependent inhibition of acetic acid writhing. The paw-licking response time was reduced both in the early and late phases of formalin nociception in a dose-dependent manner by trimethoxy flavones. A significant increase in tail withdrawal latency time was also observed after trimethoxy flavones treatment. These observations revealed the potential anti-nociceptive action of the investigated trimethoxy flavones. Pretreatment with naloxone and bicuculline significantly attenuated the reduction of abdominal constrictions produced by all the tested trimethoxy flavones indicating a definite role of opioid and GABAergic mechanisms in the anti-nociceptive effect of trimethoxy flavones. The anti-nociceptive action elicited by various trimethoxy flavones was differently modulated by glibenclamide, ondansetron, yohimbine and sulpiride.The investigated trimethoxy flavones exhibited promising anti-nociceptive activity in various nociceptive models, and multiple mechanisms are involved in the anti-nociceptive activity of these compounds.

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