scholarly journals The Thrombolytic and Cytotoxic Effects of Nigella sativa (L.) Seeds: The Prophetic Medicine

2020 ◽  
Vol 2 (2) ◽  
pp. 70-77
Author(s):  
Zahir Uddin Mohammed Babar ◽  
Irwandi Jaswir ◽  
Mohd Hafidz Mahamad Maifiah ◽  
Soraya Ismail ◽  
Raha Ahmad Raus ◽  
...  
Keyword(s):  
Brine Shrimp ◽  
Nigella Sativa ◽  
Blood Clot ◽  
Artemia Salina ◽  
Water Soluble ◽  
Clot Lysis ◽  
Dependent Manner ◽  
Cytotoxic Effects ◽  
Thrombolytic Effect ◽  
Dose Dependent

The Water-Soluble Extract (WSE) is a crude bioactive phytoconstituent of Nigella sativa (L.) seeds discovered recently. The current findings report about the thrombolytic and cytotoxic effects of WSE using human blood clot lysis and brine shrimp lethality (BSL) bioassay. The thrombolytic effect of WSE (1,666.67 µg/mL) was determined via the clot and lysate weight measurements compared to streptokinase (STK) of 30,000 IU/mL and normal saline (NS) while the cytotoxicity of WSE (44.14-2,000 µg/mL) against vincristine sulfate (VCS;3.125-100 µg/mL). WSE has shown extremely statistically significant (p<0.0001) clot lysis (90.00%) compared to NS (3.76%) whilst it was also significantly different (p<0.0063) to STK (72.41%) exhibiting LC50 of 1,795.90 µg/mL vs. VCS (39.25 µg/mL) in a dose-dependent manner. The current results suggested WSE has a potent thrombolytic effect with mild dose-dependent cytotoxicity towards brine shrimp nauplii (Artemia salina). It also suggested WSE might have enzymatic roles on thrombin, fibrin, and plasmin of blood. This pharmacological action of WSE is might be due to its antioxidant property, short-chain fatty acids and/or amino acids. Further studies are highly recommended on the enzymatic role(s) and bioactive phytoconstituents of WSE.

scholarly journals Inactivation of purified human alpha 2-antiplasmin and purified human C1 inhibitor by synthetic fibrinolytic agents

Blood ◽  
1981 ◽  
Vol 57 (6) ◽  
pp. 1015-1024
Author(s):  
LA Miles ◽  
JP Burnier ◽  
MS Verlander ◽  
M Goodman ◽  
AJ Kleiss ◽  
...  
Keyword(s):  
Blood Clot ◽  
Water Soluble ◽  
Flufenamic Acid ◽  
Clot Lysis ◽  
Dependent Manner ◽  
Plasmin Activity ◽  
Concentration Dependent Manner ◽  
Factor Xiia ◽  
Fibrinolytic Compounds

3-Hydroxypropyl flufenamide (Flu-HPA) is one of a series of flufenamic acid derivatives that enhances blood clot lysis in vitro. Studies of possible mechanisms of action of Flu-HPA were undertaken. The profibrinolytic activity of Flu-HPA in clot lysis assays was found to be dependent on plasminogen. The influence of Flu-HPA on the ability of purified alpha 2-antiplasmin to inhibit purified plasmin was studied. Plasmin activity was determined using 125I-fibrin plates or the spectrophotometric tripeptide substrate, Val-Leu-Lys-paranitroanilide. At Flu-HPA concentrations greater than 1 mM, the inhibitory activity of alpha 2-antiplasmin was abolished in a time-dependent and concentration- dependent manner. The influence of Flu-HPA on the ability of purified Cl inhibitor to inhibit purified plasma kallikrein and beta-Factor XIIa was also studied. Cl inhibitor activity was abolished by Flu-HPA at concentrations greater than 2 mM. Notably, Flu-HPA up to 60 mM did not affect the amidolytic activities of plasmin, kallikrein, or beta-Factor XIIa. Flu-HPA did not release enzyme activity from preformed complexes of either alpha 2-antiplasmin and plasmin of Cl inhibitor and kallikrein. A water-soluble derivative of flufenamic acid, N-flufenamyl- glutamic acid, also inactivated alpha 2-antiplasm and Cl inhibitor. This inactivation was shown to be reversible. These results indicate that synthetic fibrinolytic compounds such as flufenamic acid derivatives may promote fibrinolysis by directly inactivating alpha 2- antiplasmin and Cl inhibitor.

scholarly journals Inactivation of purified human alpha 2-antiplasmin and purified human C1 inhibitor by synthetic fibrinolytic agents

Blood ◽  
1981 ◽  
Vol 57 (6) ◽  
pp. 1015-1024 ◽  
Author(s):  
LA Miles ◽  
JP Burnier ◽  
MS Verlander ◽  
M Goodman ◽  
AJ Kleiss ◽  
...  
Keyword(s):  
Blood Clot ◽  
Water Soluble ◽  
Flufenamic Acid ◽  
Clot Lysis ◽  
Dependent Manner ◽  
Plasmin Activity ◽  
Concentration Dependent Manner ◽  
Factor Xiia ◽  
Fibrinolytic Compounds

Abstract 3-Hydroxypropyl flufenamide (Flu-HPA) is one of a series of flufenamic acid derivatives that enhances blood clot lysis in vitro. Studies of possible mechanisms of action of Flu-HPA were undertaken. The profibrinolytic activity of Flu-HPA in clot lysis assays was found to be dependent on plasminogen. The influence of Flu-HPA on the ability of purified alpha 2-antiplasmin to inhibit purified plasmin was studied. Plasmin activity was determined using 125I-fibrin plates or the spectrophotometric tripeptide substrate, Val-Leu-Lys-paranitroanilide. At Flu-HPA concentrations greater than 1 mM, the inhibitory activity of alpha 2-antiplasmin was abolished in a time-dependent and concentration- dependent manner. The influence of Flu-HPA on the ability of purified Cl inhibitor to inhibit purified plasma kallikrein and beta-Factor XIIa was also studied. Cl inhibitor activity was abolished by Flu-HPA at concentrations greater than 2 mM. Notably, Flu-HPA up to 60 mM did not affect the amidolytic activities of plasmin, kallikrein, or beta-Factor XIIa. Flu-HPA did not release enzyme activity from preformed complexes of either alpha 2-antiplasmin and plasmin of Cl inhibitor and kallikrein. A water-soluble derivative of flufenamic acid, N-flufenamyl- glutamic acid, also inactivated alpha 2-antiplasm and Cl inhibitor. This inactivation was shown to be reversible. These results indicate that synthetic fibrinolytic compounds such as flufenamic acid derivatives may promote fibrinolysis by directly inactivating alpha 2- antiplasmin and Cl inhibitor.

Pharmacognostical Standardization and Pharmacological Potential of Elaeocarpus ganitrus Leaves as an Antiulcer Agent

2018 ◽  
Vol 11 (4) ◽  
pp. 4162-4169
Author(s):  
Mayank Kulshreshtha ◽  
Manjul Pratap Singh
Keyword(s):  
Skin Diseases ◽  
Scientific Data ◽  
Water Soluble ◽  
Histopathological Analysis ◽  
Phytochemical Analysis ◽  
Dependent Manner ◽  
Soluble Extract ◽  
Biochemical Studies ◽  
Pharmacological Potential ◽  
Dose Dependent

Elaeocarpus ganitrus Roxb, (E. ganitrus) known as Rudraksha belongs to family- Eleocarpaceae. It has a reflecting position in Hinduism and Ayurveda whereas traditionally it has mentioned to cure various health problems like fever, skin diseases, mental problems, wound healing etc. The present study was designed to study the microscopic and macroscopic analysis, physiochemical parameters, quantitative microscopy, phytochemical screening of E. ganitrus leaves as per WHO guidelines and evaluate the antiulcer potential of aqueous extract of E. ganitrus (AEEG) and ethanolic extract of E. ganitrus (EEEG) at the doses of 200 mg/kg and 400 mg/kg using pylorus ligation induced ulcers model, biochemical parameters. Hepatic, cardiac, hematological parameters have also done to find out the effect of different extracts on other major organs. Microscopic analysis proved the presence of covering trichomes, upper epidermis, lower epidermis, stomata, phloem, xylem etc. Ash value, water soluble ash, acid soluble ash, water soluble extract, alcohol soluble extract, loss on drying, swelling index, foaming index found to be 4.3 ± 0.52, 0.2 ± 0.33, 2.0 ± 0.2, 13.7 ± 0.25, 12.5 ± 0.55, 9.8 ± 0.23, 3.6 ± 0.04, more than 100. Different quantitative parameters were found out. Phytochemical analysis of different extracts showed the presence of various primary and secondary metabolite like alkaloids, glycosides, tannin, phenolic compounds etc. Pharmacological potential showed that extracts treated, and sucralfate treated groups showed significantly decreases in ulcer index in all above-mentioned models, biochemical studies clearly showed significant decreases in volume, pH, free acidity, total acidity of gastric content and increases in gastric mucus parameters like protein, total hexoses, hexosamine, fucose, sialic acid and DNA level. The level of antioxidant enzymes like LPO (Lipid peroxidation), SOD (Superoxide dimutase) were decreased and CAT (Catalase) level was increased. Level of PC (Plasma corticosterone) was decreased. Hematological, hepatic, cardiac parameters found to be normal during extracts treatment. Histopathological analysis clearly supports the biochemical studies at various doses and it was found to be effective in dose dependent manner. The obtained scientific data may be helpful to prepare the monograph of the plant and E. ganitrus has antiulcer potential in a dose dependent. Detailed study needed for better exposure of plant.

scholarly journals In vivo and in vitro antiplasmodial activities of some plants traditionally used in Guatemala against malaria.

1997 ◽  
Vol 41 (7) ◽  
pp. 1500-1503 ◽  
Author(s):  
F F Franssen ◽  
L J Smeijsters ◽  
I Berger ◽  
B E Medinilla Aldana
Keyword(s):  
Plasmodium Berghei ◽  
Brine Shrimp ◽  
Folk Medicine ◽  
Artemia Salina ◽  
In Vitro Cultures ◽  
Cytotoxic Effects ◽  
Resistant Strains ◽  
Simarouba Glauca

We present an evaluation of the antiplasmodial and cytotoxic effects of four plants commonly used in Guatemalan folk medicine against malaria. Methanol extracts of Simarouba glauca D. C., Sansevieria guineensis Willd, Croton guatemalensis Lotsy, and Neurolaena lobata (L.)R.Br. significantly reduced parasitemias in Plasmodium berghei-infected mice. Dichloromethane fractions were screened for their cytotoxicities on Artemia salina (brine shrimp) larvae, and 50% inhibitory concentrations were determined for Plasmodium falciparum in in vitro cultures. Both chloroquine-susceptible and -resistant strains of P. falciparum were significantly inhibited by these extracts. Of all dichloromethane extracts, only the S. glauca cortex extract was considered to be toxic to nauplii of A. salina in the brine shrimp test.

scholarly journals TB-4 Antitumor effects of a novel curcumin derivative curcumin monoglucuronide on glioblastoma cells in vitro and in vivo

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi6-vi6
Author(s):  
Takashi Fujii ◽  
Shun Yamamuro ◽  
Masamichi Takahashi ◽  
Akihide Kondo ◽  
Yoshitaka Narita ◽  
...  
Keyword(s):  
Cell Death ◽  
Water Soluble ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Multiple Cell ◽  
Human Gbm ◽  
Dose Dependent ◽  
Novel Therapeutic

Abstract The therapeutic outcome of glioblastomas (GBMs) is still very poor. Therefore, invention of novel therapeutic methods against GBM cases is considered urgent. The antitumor effects of naturally-derived compounds are attracting attention recently, and therapeutic efficacy of curcumin, a plant-derived compound previously used for multiple purpose, has been indicated in many cancer systems; however, clinical application of curcumin is considered difficult because of its poor bioavailability (under 1 %). Curcumin monoglucuronide (CMG), a water-soluble prodrug of curcumin recently developed for overcoming this weakness, has been demonstrated excellent antitumor effects for several malignancies in vitro and in vivo; therefore, we investigated the effects of CMG against GBM cells. CMG induced cell death of human GBM cells lines (T98G, U251MG, and U87MG) by dose dependent manner by triggering multiple forms of cell death such as apoptosis and perthanatos. Immunoblotting of CMG-treated GBM cell lysates demonstrated activation of multiple cell death signaling. Furthermore, immunodeficiency mice harboring intracerebral U87MG cell xenografts systemically treated by CMG showed significantly prolonged survival compared with control mice. These results suggest CMG would be a novel therapeutic agent against GBM cases.

Identification and characterisation of monoclonal antibodies that impair the activation of human thrombin activatable fibrinolysis inhibitor through different mechanisms

2011 ◽  
Vol 106 (07) ◽  
pp. 90-101 ◽  
Author(s):  
Niraj Mishra ◽  
Ellen Vercauteren ◽  
Jan Develter ◽  
Riet Bammens ◽  
Paul J. Declerck ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Clot Lysis ◽  
Dependent Manner ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Lysis Time ◽  
Human Thrombin ◽  
Fibrinolysis Inhibitor ◽  
Dose Dependent ◽  
Clot Lysis Time

SummaryThrombin activatable fibrinolysis inhibitor (TAFI) forms a molecular link between coagulation and fibrinolysis and is a putative target to develop profibrinolytic drugs. Out of a panel of monoclonal antibodies (MA) raised against TAFI-ACIIYQ, we selected MA-TCK11A9, MA-TCK22G2 and MA-TCK27A4, which revealed high affinity towards human TAFITI- wt. MA-TCK11A9 was able to inhibit mainly plasmin-mediated TAFI activation, MA-TCK22G2 inhibited plasmin- and thrombin-mediated TAFI activation and MA-TCK27A4 inhibited TAFI activation by plasmin, thrombin and thrombin/thrombomodulin (T/TM) in a dose-dependent manner. These MA did not interfere with TAFIa activity. Using an eightfold molar excess of MA over TAFI, all three MA were able to reduce clot lysis time significantly, i.e. in the presence of exogenous TM, MATCK11A9, MA-TCK22G2 and MA-TCK27A4 reduced clot lysis time by 47 ± 9.1%, 80 ± 8.6% and 92 ± 14%, respectively, compared to PTCI. This effect was even more pronounced in the absence of TM i.e. MATCK11A9, MA-TCK22G2 and MA-TCK27A4 reduced clot lysis time by 90 ± 14%, 140 ± 12% and 147 ± 29%, respectively, compared to PTCI. Mutagenesis analysis revealed that residues at position 268, 272 and 276 are involved in the binding of MA-TCK11A9, residues 147 and 148 in the binding of MA-TCK22G2 and residue 113 in the binding of MATCK27A4. The present study identified three MA, with distinct epitopes, that impair the activation of human TAFI and demonstrated that MATCK11A9 which mainly impairs plasmin-mediated TAFI activation can also reduce significantly clot lysis time in vitro.

Cytotoxic effects of cisplatin, cis-dichlorodiammineplatinum(II), on Tetrahymena

1988 ◽  
Vol 90 (4) ◽  
pp. 707-716
Author(s):  
J.R. Nilsson
Keyword(s):  
Mitochondrial Membrane ◽  
Prolonged Treatment ◽  
Dependent Manner ◽  
Inner Mitochondrial Membrane ◽  
Cell Organelles ◽  
Cell Content ◽  
Cytotoxic Effects ◽  
Dense Granules ◽  
High Concentrations ◽  
Dose Dependent

A study was made of the effects of cisplatin, cis-dichlorodiammineplatinum(II) (5–250 mg l-1), on the physiology and fine structure of Tetrahymena. The physiological effects observed were dose-dependent. Endocytosis was inhibited reversibly in all, but late in the high, concentrations. After an initial dose-related increase, due to division of cells most advanced in the cell cycle, proliferation ceased for at least two normal cell generations (6 h) in 50 and 100 mg drug l-1, but for 24 h in 250 mg l-1, after which multiplication was resumed in a dose-dependent manner. Exposure to cisplatin resulted in the appearance of small, refractive granules and platinum (i.e. electron-dense material) accumulated in these granules. Fine structural observations of cells exposed to 250 mg drug l-1 showed nucleolar fusion and appearance initially of lipid droplets, dense granules and autophagosomes. A time-dependent redistribution of cell organelles was revealed by morphometry; in particular, the mitochondria increased in number, but decreased in size. Moreover, after prolonged treatment (24 h) and without cell division, the inner mitochondrial membrane had diminished and the ratio of the inner to the outer mitochondrial membrane was only half of the value for control mitochondria. Concomitantly with this decrease, the cell content of ATP was reduced to a similar extent. The findings indicate a specific action of cisplatin on mitochondria, resembling that induced in Tetrahymena by chloramphenicol and methotrexate.

scholarly journals Cytotoxic Effects of Air Freshener Biocides in Lung Epithelial Cells

2013 ◽  
Vol 8 (9) ◽  
pp. 1934578X1300800
Author(s):  
Jung-Taek Kwon ◽  
Mimi Lee ◽  
Gun-Baek Seo ◽  
Hyun-Mi Kim ◽  
Ilseob Shim ◽  
...  
Keyword(s):  
Dna Damage ◽  
Epithelial Cells ◽  
Cell Viability ◽  
Lung Epithelial Cells ◽  
Ros Generation ◽  
Dependent Manner ◽  
Cytotoxic Effects ◽  
Lung Epithelial ◽  
Dose Dependent ◽  
A549 Lung

This study evaluated the cytotoxicity of mixtures of citral (CTR) and either benzisothiazolinone (BIT, Mix-CTR-BIT) or triclosan (TCS, Mix-CTR-TCS) in human A549 lung epithelial cells. We investigated the effects of various mix ratios of these common air freshener ingredients on cell viability, cell proliferation, reactive oxygen species (ROS) generation, and DNA damage. Mix-CTR-BIT and Mix-CTR-TCS significantly decreased the viability of lung epithelial cells and inhibited cell growth in a dose-dependent manner. In addition, both mixtures increased ROS generation, compared to that observed in control cells. In particular, cell viability, growth, and morphology were affected upon increase in the proportion of BIT or TCS in the mixture. However, comet analysis showed that treatment of cells with Mix-CTR-BIT or Mix-CTR-TCS did not increase DNA damage. Taken together, these data suggested that increasing the content of biocides in air fresheners might induce cytotoxicity, and that screening these compounds using lung epithelial cells may contribute to hazard assessment.

scholarly journals Evaluation of analgesic, neuropharmacological and cytotoxic activity of Trigonella foenum-graecum Linn.

1970 ◽  
Vol 1 (1) ◽  
pp. 6-11
Author(s):  
Moli Akter ◽  
Mirola Afroze ◽  
Ambia Khatun
Keyword(s):  
Acetic Acid ◽  
Brine Shrimp ◽  
Dependent Manner ◽  
Immersion Method ◽  
Standard Drug ◽  
Writhing Test ◽  
Trigonella Foenum Graecum ◽  
Vincristine Sulphate ◽  
Tail Immersion ◽  
Dose Dependent

The present study was carried out to investigate the possible analgesic, neuropharmacological and cytotoxic activities of the methanolic extract of Trigonella foenum-graecum Linn. leaves. The analgesic and neuropharmacological activities of Trigonella foenum-graecum Linn. were investigated at the doses of 100mg/kg, 200mg/kg and 400mg/kg of body weight in mice. Analgesic potential of the extract was evaluated for centrally acting analgesic property using tail immersion method and peripheral analgesic actions using acetic acid-induced writhing test. In acetic acid-induced writhing test, extract produced a significant (p < 0.001) inhibition of writhing response in a dose dependent manner but maximum inhibition (93.46%) of writhing was found at 400mg/kg dose. In tail immersion method, extract caused a significant (p < 0.001) increase in latency time and the results were comparable to the standard drug Diclofenac- Sodium. In addition, neuropharmacological property of crude extract was carried out by Hole cross and Open field test. The extract significantly (p < 0.05-0.001) displayed a dose dependent suppression of motor activity, exploratory behaviour. Furthermore, the extract was subjected to Brine Shrimp lethality bioassay for primary evaluation of cytotoxicity, where the extract was found to be highly toxic to Brine Shrimp nauplii, having LC50 values of 10μg/ml while the LC50 of the reference anticancer drug vincristine sulphate was 0.66μg/ml. The results of this present study suggest that the extract possesses analgesic, cytotoxic and CNS depressant activities. Key Words: Trigonella foenum-graecum Linn.; cytotoxicity; neuropharmacological; analgesic activity. DOI: http://dx.doi.org/10.3329/icpj.v1i1.9218 International Current Pharmaceutical Journal 2011, 1(1): 6-11

Comparative Fibrinolytic Properties of Staphylokinase and Streptokinase in Animal Models of Venous Thrombosis

1991 ◽  
Vol 66 (04) ◽  
pp. 468-473 ◽  
Author(s):  
H R Lijnen ◽  
J M Stassen ◽  
I Vanlinthout ◽  
H Fukao ◽  
K Okada ◽  
...  
Keyword(s):  
Human Plasma ◽  
Pulmonary Embolus ◽  
Blood Clot ◽  
B Value ◽  
Clot Lysis ◽  
Maximal Rate ◽  
Pharmacokinetic Properties ◽  
Z Value ◽  
Dose Dependent

SummaryThe thrombolytic and pharmacokinetic properties of staphylokinase were compared with those of streptokinase in hamsters with a pulmonary embolus produced from human plasma or from hamster plasma, and in rabbits with a jugular vein blood clot produced from rabbit blood. In both models, a continuous intravenous infusion of staphylokinase and streptokinase over 60 min in hamsters or over 4 h in rabbits, induced dose-dependent progressive clot lysis in the absence of significant systemic activation of the fibrinolytic system. The results of thrombolytic potency (clot lysis at 30 min after the end of the infusion, in percent, versus dose administered, in mg/kg) were fitted with an exponentially transformed sigmoidal function and the maximal percent clot lysis (c), the maximal rate of lysis (z = ¼ac · e b ) and the dose at which the maximal rate of lysis is achieved (b) were determined. In hamsters with a pulmonary embolus produced from human plasma, streptokinase had a somewhat higher thrombolytic potency than staphylokinase, as revealed by a higher z value (2,100 ± 1,100% lysis per mg/kg streptokinase administered versus 1,100 ± 330% lysis per mg/kg for staphylokinase). In hamsters with a pulmonary embolus produced from hamster plasma, staphylokinase had a somewhat higher thrombolytic potency than streptokinase (z = 1,600 ± 440 versus 1,200 ± 370% lysis per mg/kg). Staphylokinase had a higher thrombolytic potency than streptokinase in rabbits, as revealed by a higher z-value (950 ± 350% lysis per mg/kg staphylokinase administered versus 330 ± 39% lysis per mg/kg for streptokinase) and a lower b-value (0.035 ± 0.010 mg/kg staphylokinase versus 0.091 ± 0.008 mg/kg for streptokinase). The plasma clearance following bolus injection of staphylokinase or streptokinase in hamsters or rabbits was comparably rapid (1.1 to 1.4 ml/min in hamsters and 14 to 15 ml/min in rabbits) as a result of a short initial half-life (1.8 to 1.9 min in hamsters and 1.7 to 2.0 min in rabbits). These results in two quantitative rodent models of thrombolysis suggest that staphylokinase is a potent thrombolytic agent with an in vivo thrombolytic potency that is comparable to that of streptokinase. Further investigation of the thrombolytic potential of staphylokinase seems to be warranted.

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