scholarly journals Phytochemical Evaluation, Embryotoxicity, and Teratogenic Effects of Curcuma longa Extract on Zebrafish (Danio rerio)

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Akinola Adekoya Alafiatayo ◽  
Kok-Song Lai ◽  
Ahmad Syahida ◽  
Maziah Mahmood ◽  
Noor Azmi Shaharuddin
Keyword(s):  
Methanol Extract ◽  
Therapeutic Potential ◽  
Curcuma Longa ◽  
Therapeutic Index ◽  
Teratogenic Effects ◽  
Physical Body ◽  
Toxicity Analysis ◽  
Dose Dependent ◽  
Higher Doses ◽  
Toxicity Effects

Curcuma longa L. is a rhizome plant often used as traditional medicinal preparations in Southeast Asia. The dried powder is commonly known as cure-all herbal medicine with a wider spectrum of pharmaceutical activities. In spite of the widely reported therapeutic applications of C. longa, research on its safety and teratogenic effects on zebrafish embryos and larvae is still limited. Hence, this research aimed to assess the toxicity of C. longa extract on zebrafish. Using a reflux flask, methanol extract of C. longa was extracted and the identification and quantification of total flavonoids were carried out with HPLC. Twelve fertilized embryos were selected to test the embryotoxicity and teratogenicity at different concentration points. The embryos were exposed to the extract in the E3M medium while the control was only exposed to E3M and different developmental endpoints were recorded with the therapeutic index calculated using the ratio of LC50/EC50. C. longa extract was detected to be highly rich in flavonoids with catechin, epicatechin, and naringenin as the 3 most abundant with concentrations of 3,531.34, 688.70, and 523.83μg/mL, respectively. The toxicity effects were discovered to be dose-dependent at dosage above 62.50μg/mL, while, at 125.0μg/mL, mortality of embryos was observed and physical body deformities of larvae were recorded among the hatched embryos at higher concentrations. Teratogenic effect of the extract was severe at higher concentrations producing physical body deformities such as kink tail, bend trunk, and enlarged yolk sac edema. Finally, the therapeutic index (TI) values calculated were approximately the same for different concentration points tested. Overall, the result revealed that plants having therapeutic potential could also pose threats when consumed at higher doses especially on the embryos. Therefore, detailed toxicity analysis should be carried out on medicinal plants to ascertain their safety on the embryos and its development.

scholarly journals Phytochemical evaluation, Embryotoxicity and Teratogenic effects of Curcuma longa extract in Zebrafish (Danio rerio)

2019 ◽  
Author(s):  
Alafiatayo Akinola Adekoya ◽  
Kok-Song Lai ◽  
Ahmad Syahida ◽  
Maziah Mahmood ◽  
Noor Azmi Shaharuddin
Keyword(s):  
Methanol Extract ◽  
Therapeutic Potential ◽  
Curcuma Longa ◽  
Therapeutic Index ◽  
Teratogenic Effects ◽  
Physical Body ◽  
Toxicity Analysis ◽  
Dose Dependent ◽  
Higher Doses ◽  
Toxicity Effects

AbstractCurcuma longa L. is a rhizome plant often used as traditional medicinal preparations in Southeast Asia. The dried powder is commonly known as cure-all herbal medicine with a wider spectrum of pharmaceutical activities. In spite of the widely reported therapeutic applications of C. longa, research on its safety and teratogenic effects on zebrafish embryos and larvae is still limited. Hence, this research was aimed to assess the toxicity of C. longa extract on zebrafish. Using a reflux flask, methanol extract of C. longa was extracted and the identification and quantification of total flavonoids were carried out with HPLC. Twelve fertilized embryos were selected to test the embryotoxicity and teratogenicity at different concentration points. The embryos were exposed to the extract in the E3M medium while the control was only exposed to E3M and different developmental endpoints were recorded with the therapeutic index calculated using the ratio of LC50/EC50. C. longa extract was detected to be highly rich in flavonoids with catechin, epicatechin and naringenin as the 3 most abundant with concentrations of 3,531.34, 688.70 and 523.83μg/mL respectively. The toxicity effects were discovered to be dose-dependent at dosage above 62.50μg/mL, while at 125.0μg/mL, mortality of embryos was observed and physical body deformities of larvae was recorded among the hatched embryos at higher concentrations. Teratogenic effect of the extract was severe at higher concentrations producing physical body deformities such as kink tail, bend trunk, enlarged yolk sac edema. Finally, the Therapeutic Index (TI) values calculated were approximately same for different concentration points tested. Overall, the result revealed that plants having therapeutic potential could also pose threats when consumed at higher doses especially on the embryos. Therefore, detailed toxicity analysis should be carried out on medicinal plants to ascertain their safety on the embryos and its development.

scholarly journals Genotoxic and antigenotoxic potential of the Lagenandra toxicaria Dalz. rhizome methanol extract using Allium cepa assay.

2021 ◽  
Author(s):  
AKARSHA B ◽  
KRISHNAKUMAR GULIMANE
Keyword(s):  
Allium Cepa ◽  
Methanol Extract ◽  
Histochemical Staining ◽  
Biochemical Changes ◽  
Root Tip ◽  
Dna Integrity ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Higher Doses

Abstract This study is the first ever approach to evaluate the possible genotoxic effect of the Lagenandra toxicaria rhizome methanol extract and its antigenotoxic potency against 3% H2O2 induced genetic damage on Allium cepa root tip model. The assay revealed a significant decrease in mitotic index (MI) and an increase in the percentage of clastogenicity in a time and dose-dependent manner in the roots exposed to Lagenandra toxicaria extract at 0.2 mg/ml, 0.5 mg/ml, 1 mg/ml, 5 mg/ml and 10 mg/ml concentration for 1, 2 and 4hour. The ultra structures of cell surface and biochemical changes of the cells were assessed in four hour treated roots using Field emission scanning electron microscopy (FESEM) and Fourier-transform infrared spectroscopy (FTIR). The higher dose of 10 mg/ml treated roots showed an evident morphological as well as biochemical changes compared to the control. The agarose gel electrophoresis showed the loss of DNA integrity in the roots that were treated with 10 mg/ml extract for four hours, where as the control showed comparatively intact DNA bands. The in situ histochemical staining by Schiff’s reagent and nitroblueterasolium (NBT) confirmed the increased lipid peroxidation and free radical generation in four hour treated samples. Subsequently, the possible antigenotoxic potential of the plant extract was explored at its lower doses using H2O2 standard assays. The H2O2 treatment induced nuclear lesions in 93.45 ± 2.33% cells and it was seen to be reduced significantly (50.99 ±7.59 % and 37.13 ± 2.66 %) after the treatment with lower concentration of 0.01 mg/ml and 0.02 mg/ml extract respectively. This suggest that the Lagenandra toxicaria rhizome methanol extract acts as antigenotoxic agent at lower doses but at higher doses the extract induces clastogenic effects and thus acts like a janus-faced compound.

scholarly journals GENOTOXIC AND ANTIGENOTOXIC POTENTIAL OF THE LAGENANDRA TOXICARIA DALZ. RHIZOME METHANOL EXTRACT USING ALLIUM CEPA ASSAY

2021 ◽  
pp. 82-90
Author(s):  
AKARSHA B ◽  
KRISHNAKUMAR G
Keyword(s):  
Allium Cepa ◽  
Methanol Extract ◽  
Histochemical Staining ◽  
Root Tip ◽  
Dna Integrity ◽  
Dependent Manner ◽  
Soxhlet Apparatus ◽  
Dose Dependent ◽  
Higher Doses

Objective: The study is to evaluate the possible genotoxic and antigenotoxic potential of Lagenandra toxicaria rhizome methanol extract using Allium cepa root tip assay. Methods: The rhizome methanol extract was prepared using Soxhlet apparatus. The A. cepa roots were treated with various concentrations of the extract at different time points and stained with aceto-orcein. The mitotic index (MI) was calculated. Results: A significant decrease in MI and increase in the percentage of clastogenicity was observed in a time- and dose-dependent manner in the roots treated with the extract at 0.2 mg/ml, 0.5 mg/ml, 1 mg/ml, 5 mg/ml, and 10 mg/ml concentration for 1, 2, and 4 h. The field emission scanning electron microscopy and Fourier-transform infrared spectroscopy revealed evident morphological and biochemical changes at 10 mg/ml treatment when compared to control for 4 h. The agarose gel electrophoresis showed loss of DNA integrity at 10 mg/ml extract for 4 h. In situ histochemical staining by Schiff’s reagent and nitroblue tetrazolium confirmed the increased lipid peroxidation and free radical generation at 4 h treatment. Subsequently, the possible antigenotoxic potential of the plant extract was explored using H2O2 standard assays. The increased percentage of H2O2 induced nuclear lesions was reduced significantly after the modulatory treatment with extract. Conclusion: The L. toxicaria rhizome methanol extract acts as an antigenotoxic agent at lower doses and at higher doses the extract induces clastogenic effects. Further studies are needed to unravel the active component in the extract that mediates the observed phenomenon in the current study.

Involvement of 5-Hydroxytryptamine in Platelet Aggregation In Vivo in Rats and Guinea Pigs

1989 ◽  
Vol 61 (03) ◽  
pp. 463-467 ◽  
Author(s):  
G M Smith
Keyword(s):  
Platelet Count ◽  
Guinea Pigs ◽  
Platelet Adhesion ◽  
Adenosine Diphosphate ◽  
Rate Of Return ◽  
Low Doses ◽  
Dose Dependent ◽  
Higher Doses ◽  
Rat Platelets

SummaryIn this study, 5-hydroxytryptamine (5-HT) caused a dose- dependent fall in the circulating platelet count suggesting that 5-HT receptors are activated in rat platelets to cause platelet adhesion and aggregation. When low doses of adenosine diphosphate (ADP) were simultaneously injected with 5-HT, there was a significant potentiation of the responses to ADR Ketanserin significantly reduced the potentiated responses. When higher doses of ADP were infused with bolus injections of 5-HT there was no potentiation and ketanserin did not reduce these responses. Ketanserin did not inhibit the collagen-induced fall in circulating platelet count, but did significantly increase the rate of return to the basal platelet count compared with control. 5-HT did not cause a fall in platelet count in guinea-pigs

Anticoagulant Activity of Hirulog™, a Direct Thrombin Inhibitor, in Humans

1993 ◽  
Vol 69 (02) ◽  
pp. 157-163 ◽  
Author(s):  
Irving Fox ◽  
Adrian Dawson ◽  
Peter Loynds ◽  
Jane Eisner ◽  
Kathleen Findlen ◽  
...  
Keyword(s):  
Rational Design ◽  
Therapeutic Potential ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
Direct Thrombin Inhibitor ◽  
Controlled Study ◽  
Thrombin Inhibitor ◽  
Thrombin Time ◽  
Thrombotic Disease ◽  
Dose Dependent

SummaryHirulog™ (BG8967) is a direct thrombin inhibitor built by rational design using the protein hirudin as a model (Maraganore et al. [1990]; Biochemistry 29: 7095–101). In order to evaluate the therapeutic potential for hirulog in the management of thrombotic disease, the tolerability and anticoagulant activity of the agent were examined in a study of human volunteers.In a randomized, placebo-controlled study (n = 54), the intravenous infusion of hirulog over 15 min showed a rapid, dose-dependent prolongation of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). There was a corresponding dose-dependent increase in plasma hirulog levels. The peptide was rapidly cleared with a half-life of 36 min and a total body clearance rate for the peptide of 0.43 1 kg−1 h−1. Similar activity was observed following subcutaneous injection but with sustained pharmacodynamic and pharmacokinetic behavior. There was a significant correlation between pharmacokinetic and pharmacodynamic variables for both intravenous (r = 0.8, p <0.001) and subcutaneous administration (r = 0.7, p = 0.002).To evaluate the possible interactions of aspirin on the tolerability and anticoagulant activity of intravenous hirulog, a cross-over design was employed in eight subjects. Aspirin administration did not modify the peptide’s activity. At the administered dose of 0.6 mg kg−1 h−1 for 2 h, hirulog infusion prolonged APTT from 230 to 260% baseline. The infusion of hirulog in subjects who had received aspirin was not associated with any significant changes in the template bleeding time.The final phase of the study examined the activity and tolerability of hirulog in ten subjects during prolonged intravenous infusions for up to 24 h. The peptide (0.3 mg kg−1 h−1) exhibited sustained anticoagulant activity with no evidence for a cumulative effect. During hirulog infusion, APTT was prolonged from 210 to 250% baseline.In all phases of the study, hirulog administration was generally well-tolerated.Our observations show that hirulog is an active antithrombin agent with excellent tolerability in humans. As a direct thrombin inhibitor, hirulog provides a novel approach for the management of thrombotic disease.

Outcome of Treatment of Deep-Vein Thrombosis with Urokinase: Relationship to Dosage, Duration of Therapy, Age of the Thrombus and Laboratory Changes

1984 ◽  
Vol 51 (02) ◽  
pp. 236-239 ◽  
Author(s):  
A D’Angelo ◽  
P M Mannucci
Keyword(s):  
Degradation Products ◽  
High Rate ◽  
Bleeding Complications ◽  
Vein Thrombosis ◽  
Treatment Regimens ◽  
Duration Of Therapy ◽  
Laboratory Changes ◽  
Deep Vein ◽  
Dose Dependent ◽  
Higher Doses

SummaryForty-one patients with phlebographically proven DVT of the popliteal, femoral or iliac veins were treated with different regimens of urokinase (UK) given by continuous intravenous infusion. The four groups were comparable with respect to localization, extension and estimated age of the thrombi. Another phlebographic picture was taken within 48 hr after the end of UK infusion. Substantial lysis had occurred in 2 of 10 patients treated with 1500 U/kg/h for 2 days, in 4 of 11 treated with 2500/U/kg/h for 3 days, in 2 of 10 treated with 2500 U/kg/h for 7 days and in 4 of 10 treated with 4000 U/kg/h for 4 days. Only thrombi younger than 8 days could be lysed, with 61% (8/13) rate of lysis for thrombi less than 5 days old. Bleeding complications were observed more frequently with the higher doses and longer durations of therapy. The four treatment regimens all induced dose-dependent changes in fibrinogen, fibrin(ogen) degradation products, plasminogen and antiplasmin. Neither pre- nor postinfusion values of these parameters could differentiate patients with lysis from those without lysis. It is concluded that UK can provoke a high rate of thrombolysis of DVT treated early after the appearance of symptoms but that there is no relationship between UK-induced modifications of fibrinolysis and the outcome of therapy.

Ecological and physiological as well as biochemical properties of representatives of the Genus sedum L.

2014 ◽  
Vol 25 (3-4) ◽  
pp. 24-33
Author(s):  
O. I. Dzjuba ◽  
M. V. Yatsenko
Keyword(s):  
Nitric Oxide ◽  
Cell Line ◽  
Methanol Extract ◽  
Hepatoma Cell ◽  
Ethanol Extract ◽  
Biochemical Properties ◽  
Biologically Active ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Dose Dependent

The article deals with the history of the study and the current state of research of physiological and biochemical properties of the plant genus Sedum that are useful for human and has been used in folk medicine for many years. It was noticed that antioxidant properties of extracts from plants S. sarmentosum, S. sempervivoides, S. takesimense were caused by the presence of phenolic compounds. Methanol extract of plants S. takesimense exhibited strong scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals as well as significant inhibitory effects on lipid peroxidation and low density lipoprotein (LDL) oxidation induced by a metal ion Cu2+. Various immunomodulatory activities of various fractions of plants extracts (S. dendroideum, S. kamtschaticum, S. sarmentosum, S. telephium) are observed. It was shown that the ethanol extract of S. sarmentosum and it’s fractions suppressed specific antibody and cellular responses to ovalbumin in mice. The methanol extract of plants S. sarmentosum reduced the levels of anti-inflammatory markers, such as volume of exudates, number of polymorphonuclear leukocytes, suppressed nitric oxide synthesis in activated macrophages via suppressed induction of inducible nitric oxide synthase (iNOS). Polysaccharides fractions from plants S. telephium inducing productions of tumor necrosis factor alpha (TNF-α), increasing the intensity of phagocytosis in vitro and in vivo. Methanol extract from the whole part of S. kamtschaticum strongly inhibit PGE2 production from lipopolysaccharide-induced RAW 264.7 cells, a mouse macrophage cell line via modulating activity in gene expression of the enzyme cyclooxygenase-2 (COX-2). The methanol extract of plants S. sarmentosum and the major kaempferol glycosides from S. dendroideum have antinociceptive activity. It was noticed that anti-adipogenic activity of extracts from plants S. kamtschaticum were caused by inhibition of peroxisome-proliferator-activated receptor γ (PPARγ) expression and it’s dependent target genes, such as genes encoding adipocyte protein 2 (аР2), lipoprotein lipase (LPL), adiponectin and CD36. Polysaccharides fractions from S. telephium cause inhibition of cell adhesion of human fibroblast (MRC5) to laminin and fibronectin via interfere with integrin-mediated cell behaviour and they contributed to the role of polysaccharides in cell-matrix interaction. The methanol extract of plants S. sarmentosum exhibited a significant inhibitory activity in the chick embryo chorioallantoic membrane angiogenesis in a dose-dependent manner. The crude alkaloid fraction of S. sarmentosum caused a dose-dependent inhibition of cell proliferation on murine hepatoma cell line BNL CL.2 and human hepatoma cell line HepG2 without necrosis or apoptosis. Alkaloids from plants S. sarmentosum may improve survival of hepatoma patients via the inhibition of excessive growth of tumor cells. Plant’s juices have antiviral activity (S. sarmentosum, S. spurium, S. stahlii). Crude ethanol extract S. praealtum have spermicidal activity of the in mice and a relevant inhibitory effect of aqueous extract on human spermatozoa motility as well as an anti-fertilizing activity in rats. Hepatoprotective triterpenes, e.g., δ-amyrone, 3-epi-δ-amyrin, δ-amyrin and sarmentolin were isolated from S. sarmentosum. 2- and 2,6-substituted piperidine alkaloids (e.g., norsedamine, allosedridine, sedamine, allosedamine) are observed in plants S. acre, which in the presence of data on the use of pyridine and piperidine derivatives for treating neurodegenerative diseases (e.g., Alzheimer's disease), points on the promising research in this area. Taking into account that biologically active compounds are accumulated in the aboveground vegetative organs of plants of Sedum, the prospects of further study of the use of Sedum for the purposes of biotechnology and in the pharmaceutical industry becomes apparent. This work extends the existing views regarding the use of plants Sedum.

Investigation of antiulcer activity of Pergularia extensa Linn

2020 ◽  
Vol 9 (2) ◽  
pp. 23-26
Author(s):  
Pavani C H
Keyword(s):  
Cardiac Glycosides ◽  
Methanol Extract ◽  
Methanolic Extract ◽  
Antiulcer Activity ◽  
Acute Oral Toxicity ◽  
Gastric Lesions ◽  
Oral Toxicity ◽  
Control Groups ◽  
Dose Dependent

This study was based on determination of the antiulcer activity from methanol extract was prepared by using barks of pergularia extensa linn.. Priliminary investigations showed presence of saponins, terpenes, cardiac glycosides, alkaloids and sterols. Based on OECD-423 Guidelines, the pharmacology and acute oral toxicity studies were conducted by using methanolic extract. Ulcer development was prevented by Tannins because of their vasoconstriction effects and due to protein precipitation. Similarly, the Methanolic extract of Pergularia extensa Linn shows triterpenoids and saponins. The phytoconstituents are present in the extract and these could be possible agents which are involved in order to prevent gastric lesions induced by aspirin. When compared to ulcerative control groups, this Pergularia extensa Linn., shows a dose dependent curative ratio. The extracts exhibited an inhibition percentage of 27.18, 45.47 and 61.28 at doses of 100, 200 and 400mg/kg doses respectively. 

β-1, 3-Glucan attenuated chronic unpredictable mild stress induced cognitive impairment in rodents via normalizing corticosterone levels

2020 ◽  
Vol 20 ◽  
Author(s):  
Saniya Hashim Khan ◽  
Sheraz Khan ◽  
Inamullah Khan ◽  
Narmeen Hashim
Keyword(s):  
Water Maze ◽  
Memory Impairment ◽  
Glucocorticoid Receptors ◽  
Therapeutic Potential ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Neuroprotective Effects ◽  
Injurious Effect ◽  
Naturally Occurring ◽  
Dose Dependent

Background: Chronic stress elevates the cortisol beyond normal levels, which affects cognition including learning & memory. This injurious effect is primarily mediated via over excitation of metabotropic glucocorticoid receptors (mGR). Methods: The present study was aimed appraise the neuroprotective effects of naturally occurring molecule β-1,3-glucan by interfering with stress-cortisol-mGR axis. Our data of virtual screening (in silico) exhibited the promising interactions of βglucan with the mGR. Therefore, the study was extended to evaluate its efficacy (2.5, 5 and 10 mg/kg/ i.p) in an animal model of chronic unpredictable mild stress (CUMS, 28 days) induced memory impairment. Results: Results of the current study revealed the β-glucan provided dose dependent protection against deleterious effects of stress on learning and memory associated parameters observed in Morris water maze (MWM) task. At higher tested doses, it has also significantly antagonized the stress induced weight loss and corticosterone elevation. Conclusion: From these findings, it can be deduced that the β-glucan possesses therapeutic potential against stress induced memory impairment, and this effect can be attributed to its normalizing effect on corticosterone levels.

scholarly journals Nanomedicine Reformulation of Chloroquine and Hydroxychloroquine

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 175
Author(s):  
David M. Stevens ◽  
Rachael M. Crist ◽  
Stephan T. Stern
Keyword(s):  
Safety Evaluation ◽  
Therapeutic Index ◽  
Short Term ◽  
Tissue Concentrations ◽  
History Of ◽  
History Of Use ◽  
Novel Applications ◽  
Therapeutic Doses ◽  
Extensive Clinical Experience ◽  
Higher Doses

The chloroquine family of antimalarials has a long history of use, spanning many decades. Despite this extensive clinical experience, novel applications, including use in autoimmune disorders, infectious disease, and cancer, have only recently been identified. While short term use of chloroquine or hydroxychloroquine is safe at traditional therapeutic doses in patients without predisposing conditions, administration of higher doses and for longer durations are associated with toxicity, including retinotoxicity. Additional liabilities of these medications include pharmacokinetic profiles that require extended dosing to achieve therapeutic tissue concentrations. To improve chloroquine therapy, researchers have turned toward nanomedicine reformulation of chloroquine and hydroxychloroquine to increase exposure of target tissues relative to off-target tissues, thereby improving the therapeutic index. This review highlights these reformulation efforts to date, identifying issues in experimental designs leading to ambiguity regarding the nanoformulation improvements and lack of thorough pharmacokinetics and safety evaluation. Gaps in our current understanding of these formulations, as well as recommendations for future formulation efforts, are presented.

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