scholarly journals Antiplasmodial Activity of Aryltetralone Lignans from Holostylis reniformis

2007 ◽  
Vol 51 (7) ◽  
pp. 2346-2350 ◽  
Author(s):  
Valter F. de Andrade-Neto ◽  
Tito da Silva ◽  
Lucia M. Xavier Lopes ◽  
Virgílio E. do Rosário ◽  
Fernando de Pilla Varotti ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Line ◽  
Plasmodium Berghei ◽  
Resistant Strain ◽  
Lethal Dose ◽  
Hepatic Cell ◽  
Low Toxicity ◽  
Minimum Lethal Dose

ABSTRACT Extracts from Holostylis reniformis were tested in vivo against Plasmodium berghei and in vitro against a chloroquine-resistant strain of Plasmodium falciparum. The hexane extract of the roots was the most active, causing 67% reduction of parasitemia in vivo. From this extract, six lignans, including a new (7′R,8S,8′S)-3′,4′-methylenedioxy-4,5-dimethoxy-2,7′-cyclolignan-7-one, were isolated and tested in vitro against P. falciparum. The three most active lignans showed 50% inhibitor concentrations of ≤0.32 μM. An evaluation of minimum lethal dose (30%) values showed low toxicity for these lignans in a hepatic cell line (Hep G2A16). Therefore, these compounds are potential candidates for the development of antimalarial drugs.

scholarly journals A SPECIFIC POISON IN THE LIVER EXTRACTS OF RABBITS INOCULATED WITH TYPHOID AND PRODIGIOSUS BACILLI INTRAVENOUSLY

1918 ◽  
Vol 28 (5) ◽  
pp. 571-583
Author(s):  
Julia T. Parker
Keyword(s):  
Anaphylactic Shock ◽  
Liver Extract ◽  
Lethal Dose ◽  
Toxic Substance ◽  
Normal Liver ◽  
Immune Serum ◽  
Minimum Lethal Dose ◽  
Lethal Doses

1. The livers of rabbits inoculated with cultures of Bacillus typhosus or Bacillus prodigiosus under certain conditions contain a toxic substance extractable with salt solution. When the toxic extracts are injected intravenously into normal rabbits the latter animals develop symptoms resembling those of anaphylactic shock and succumb. The lethal doses of the toxic extracts are far smaller than those of normal liver extract. 2. The livers of rabbits injected with typhoid antigen also yield a toxic extract. 3. Boiling as well as filtration through a Berkefeld filter only partially detoxicates the extract. 4. Tolerance to one to two lethal doses of the poisonous extracts can be induced by cautious immunization. 5. Rabbits actively immunized to Bacillus typhosus or Bacillus prodigiosus usually resist one lethal dose of the homologous liver poison; and animals tolerant to the typhoid liver poison resist one minimum lethal dose at least of Bacillus typhosus. 6. Typhoid immune serum is not detoxicating either in vivo or in vitro for the typhoid liver poison. 7. The liver poisons are specific, since rabbits actively immunized to either Bacillus typhosus or Bacillus prodigiosus withstand at least one minimum lethal dose of the homologous but not of the heterologous-liver poisons.

Antimalarial Activity of Phenazines from Lapachol, β-Lapachone and Its Derivatives Against Plasmodium falciparum in vitro and Plasmodium berghei in vivo.

ChemInform ◽  
2004 ◽  
Vol 35 (26) ◽  
Author(s):  
Valter F. de Andrade-Neto ◽  
Marilia O. F. Goulart ◽  
Jorge F. da Silva Filho ◽  
Matuzalem J. da Silva ◽  
Maria do Carmo F. R. Pinto ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Berghei ◽  
Antimalarial Activity

scholarly journals The Development of Novel Compounds Against Malaria: Quinolines, Triazolpyridines, Pyrazolopyridines and Pyrazolopyrimidines

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4095 ◽  
Author(s):  
Luiz C. S. Pinheiro ◽  
Lívia M. Feitosa ◽  
Marilia O. Gandi ◽  
Flávia F. Silveira ◽  
Nubia Boechat
Keyword(s):  
Plasmodium Falciparum ◽  
Mouse Model ◽  
Infected Mouse ◽  
Plasmodium Berghei ◽  
Medicinal Chemistry ◽  
Quinoline Derivatives ◽  
Dihydroorotate Dehydrogenase ◽  
New Compounds

Based on medicinal chemistry tools, new compounds for malaria treatment were designed. The scaffolds of the drugs used to treat malaria, such as chloroquine, primaquine, amodiaquine, mefloquine and sulfadoxine, were used as inspiration. We demonstrated the importance of quinoline and non-quinoline derivatives in vitro with activity against the W2 chloroquine-resistant (CQR) Plasmodium falciparum clone strain and in vivo against Plasmodium berghei-infected mouse model. Among the quinoline derivatives, new hybrids between chloroquine and sulfadoxine were designed, which gave rise to an important prototype that was more active than both chloroquine and sulfadoxine. Hybrids between chloroquine–atorvastatin and primaquine–atorvastatin were also synthesized and shown to be more potent than the parent drugs alone. Additionally, among the quinoline derivatives, new mefloquine derivatives were synthesized. Among the non-quinoline derivatives, we obtained excellent results with the triazolopyrimidine nucleus, which gave us prototype I that inspired the synthesis of new heterocycles. The pyrazolopyrimidine derivatives stood out as non-quinoline derivatives that are potent inhibitors of the P. falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme. We also examined the pyrazolopyridine and pyrazolopyrimidine nuclei.

scholarly journals Andrographolide: A Novel Antimalarial Diterpene Lactone Compound fromAndrographis paniculataand Its Interaction with Curcumin and Artesunate

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Kirti Mishra ◽  
Aditya P. Dash ◽  
Nrisingha Dey
Keyword(s):  
Plasmodium Falciparum ◽  
Life Span ◽  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Andrographis Paniculata ◽  
Antiplasmodial Activity ◽  
Template Molecule

Andrographolide (AND), the diterpene lactone compound, was purified by HPLC from the methanolic fraction of the plantAndrographis paniculata. The compound was found to have potent antiplasmodial activity when tested in isolation and in combination with curcumin and artesunate against the erythrocytic stages ofPlasmodium falciparum in vitroandPlasmodium bergheiANKAin vivo. IC50s for artesunate (AS), andrographolide (AND), and curcumin (CUR) were found to be 0.05, 9.1 and 17.4 μM, respectively. The compound (AND) was found synergistic with curcumin (CUR) and addictively interactive with artesunate (AS).In vivo, andrographolide-curcumin exhibited better antimalarial activity, not only by reducing parasitemia (29%), compared to the control (81%), but also by extending the life span by 2-3 folds. Being nontoxic to thein vivosystem this agent can be used as template molecule for designing new derivatives with improved antimalarial properties.

scholarly journals In Vivo Antiplasmodial Activity of Terminalia mantaly Stem Bark Aqueous Extract in Mice Infected by Plasmodium berghei

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Mariscal Brice Tchatat Tali ◽  
Cedric Derick Jiatsa Mbouna ◽  
Lauve Rachel Yamthe Tchokouaha ◽  
Patrick Valere Tsouh Fokou ◽  
Jaures Marius Tsakem Nangap ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Aqueous Extract ◽  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Lethal Dose ◽  
Stem Bark ◽  
Antiplasmodial Activity ◽  
Bark Extract

Background. Terminalia mantaly is used in Cameroon traditional medicine to treat malaria and related symptoms. However, its antiplasmodial efficacy is still to be established. Objectives. The present study is aimed at evaluating the in vitro and in vivo antiplasmodial activity and the oral acute toxicity of the Terminalia mantaly extracts. Materials and Methods. Extracts were prepared from leaves and stem bark of T. mantaly, by maceration in distilled water, methanol, ethanol, dichloromethane (DCM), and hexane. All extracts were initially screened in vitro against the chloroquine-resistant strain W2 of P. falciparum to confirm its in vitro activity, and the most potent one was assessed in malaria mouse model at three concentrations (100, 200, and 400 mg/kg/bw). Biochemical, hematological, and histological parameters were also determined. Results. Overall, 7 extracts showed in vitro antiplasmodial activity with IC50 ranging from 0.809 μg/mL to 5.886 μg/mL. The aqueous extract from the stem bark of T. mantaly (Tmsbw) was the most potent (IC50=0.809 μg/mL) and was further assessed for acute toxicity and efficacy in Plasmodium berghei-infected mice. Tmsbw was safe in mice with a median lethal dose (LD50) higher than 2000 mg/kg of body weight. It also exerted a good antimalarial efficacy in vivo with ED50 of 69.50 mg/kg and had no significant effect on biochemical, hematological, and histological parameters. Conclusion. The results suggest that the stem bark extract of T. mantaly possesses antimalarial activity.

Plants as Sources of Antimalarial Drugs, Part 4: Activity of Brucea javanica Fruits Against Chloroquine-Resistant Plasmodium falciparum in vitro and Against Plasmodium berghei in vivo

1987 ◽  
Vol 50 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Melanie J. O'Neill ◽  
Dorothy H. Bray ◽  
Peter Boardman ◽  
Kit L. Chan ◽  
J. David Phillipson ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Berghei ◽  
Antimalarial Drugs ◽  
Brucea Javanica

scholarly journals Food Safety and Nutraceutical Potential of Caramel Colour Class IV Using In Vivo and In Vitro Assays

Foods ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 392 ◽  
Author(s):  
Marcos Mateo-Fernández ◽  
Pilar Alves-Martínez ◽  
Mercedes Del Río-Celestino ◽  
Rafael Font ◽  
Tania Merinas-Amo ◽  
...  
Keyword(s):  
Food Safety ◽  
Cell Line ◽  
Methylation Status ◽  
Lethal Dose ◽  
In Vitro Assays ◽  
Leukaemia Cell Line ◽  
Colour Class ◽  
Class Iv

Nutraceutical activity of food is analysed to promote the healthy characteristics of diet where additives are highly used. Caramel is one of the most worldwide consumed additives and it is produced by heating natural carbohydrates. The aim of this study was to evaluate the food safety and the possible nutraceutical potential of caramel colour class IV (CAR). For this purpose, in vivo toxicity/antitoxicity, genotoxicity/antigenotoxicity and longevity assays were performed using the Drosophila melanogaster model. In addition, cytotoxicity, internucleosomal DNA fragmentation, single cell gel electrophoresis and methylation status assays were conducted in the in vitro HL-60 human leukaemia cell line. Our results reported that CAR was neither toxic nor genotoxic and showed antigenotoxic effects in Drosophila. Furthermore, CAR induced cytotoxicity and hipomethylated sat-α repetitive element using HL-60 cell line. In conclusion, the food safety of CAR was demonstrated, since Lethal Dose 50 (LD50) was not reached in toxicity assay and any of the tested concentrations induced mutation rates higher than that of the concurrent control in D. melanogaster. On the other hand, CAR protected DNA from oxidative stress provided by hydrogen peroxide in Drosophila. Moreover, CAR showed chemopreventive activity and modified the methylation status of HL-60 cell line. Nevertheless, much more information about the mechanisms of gene therapies related to epigenetic modulation by food is necessary.

A Database of IC50 Values and Principal Component Analysis of Results from Six Basal Cytotoxicity Assays, for Use in the Modelling of the In Vivo and In Vitro Data of the EU ACuteTox Project

2008 ◽  
Vol 36 (5) ◽  
pp. 503-519 ◽  
Author(s):  
Richard Clothier ◽  
Paul Dierickx ◽  
Thaly Lakhanisky ◽  
Myriam Fabre ◽  
Monica Betanzos ◽  
...  
Keyword(s):  
Principal Component Analysis ◽  
Cell Line ◽  
Principal Component ◽  
Hepatic Cell ◽  
In Vitro Assays ◽  
Ic50 Values ◽  
Basal Cytotoxicity ◽  
The Eu

The main aim of the ACuteTox project (part of the EU 6th Framework programme) is to demonstrate that animal tests for acute systemic toxicity can be replaced by alternative in vitro assays. In this project, data for 97 reference chemicals were collected in the AcuBase database, designed to handle deposited in vitro and in vivo (human and animal) data. To demonstrate the applicability of in vitro basal cytotoxicity tests and in vitro– in vivo modelling, it was deemed necessary to obtain data that were generated via defined standard operating procedures. The molar basal cytotoxicity IC50 values (the 50% inhibitory concentrations for the endpoint measured) for a mouse fibroblast cell line (3T3), a human hepatic cell line (HepG2), a rat hepatic cell line (Fa32), and a human neutrophil cell line (HL-60), were compared, and gave an R2 correlation of 0.83. To identify chemicals that showed differential cytotoxicity to the various cell types involved, principal component analysis (PCA) was undertaken independently, once all the results had been returned. This showed that colchicine, cycloheximide, digoxin, 5-fluorouracil and hexachlorobenzene gave the lowest correlations with the first score vector of the PCA. The results presented are to be used to identify outliers that need to be further studied via the use of tissue-specific in vitro assays.

scholarly journals THE ACTION OF ETHYLHYDROCUPREIN (OPTOCHIN) ON TYPE STRAINS OF PNEUMOCOCCI IN VITRO AND IN VIVO, AND ON SOME OTHER MICROORGANISMS IN VITRO

1915 ◽  
Vol 22 (3) ◽  
pp. 269-285 ◽  
Author(s):  
Henry F. Moore
Keyword(s):  
Protective Action ◽  
Lethal Dose ◽  
Pneumococcal Infection ◽  
Streptococcus Group ◽  
Quinine Hydrochloride ◽  
The One ◽  
Minimum Lethal Dose ◽  
Type Strains

1. Ethylhydrocuprein hydrochloride in very high dilution inhibits the growth of, and in 18 hours kills, representatives of all four groups of pneumococci in vitro. The killing effect is generally seen in somewhat lower dilutions than the inhibiting effect. No constant or considerable difference is seen in these actions on representatives of the four groups of the pneumococci. The action of ethylhydrocuprein hydrochloride on the pneumococci in vitro is so strongly specific that it may possibly be used as a test for a true pneumococcus. 2. The inhibitory or killing effects of ethylhydrocuprein hydrochloride in vitro on bacteria other than pneumococci are slight or absent. The effects are greater on streptococci than on any other organisms examined, but are still much less than on the pneumococci. This action distinguishes between the streptococcus group, including Streptococcus mucosus sometimes found in normal mouths, on the one hand, and the true pneumococcus (including Pneumococcus mucosus), on the other. 3. Quinine hydrochloride inhibits the growth of, and kills the pneumococcus in vitro; much stronger concentrations, however, are necessary than in the case of ethylhydrocuprein. This effect of quinine hydrochloride is also seen on other organisms, but in a less degree. 4. Ethylhydrocuprein (optochin base) has a well marked protective action against experimental pneumococcal infection in mice in the case of type strains of all four groups of pneumococci; this protective action may be efficient against many multiples of the minimum lethal dose.

scholarly journals Use of An In Silico Knowledge Discovery Approach To Translate Mechanistic Studies of Silver Nanoparticles-Induced Toxicity From In Vitro To In Vivo

2021 ◽  
Author(s):  
Bin-Hsu Mao ◽  
Yi-Kai Luo ◽  
Bour-Jr W ◽  
Fong-Yu Cheng ◽  
Yu-Hsuan Lee ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Knowledge Discovery ◽  
Cell Line ◽  
In Silico ◽  
Lethal Dose ◽  
Knowledge Discovery In Databases ◽  
Morphological Observation ◽  
M Cell

Abstract Background: Silver nanoparticles (AgNPs) are considered a double-edged sword that demonstrates beneficial and harmful effects depending on their dimensions and surface coating types. However, mechanistic reports regarding size- and coating-dependent effects of AgNPs remain inadequate in vitro and in vivo. In keeping with the 3Rs principles, we adopted an in silico decision tree-based knowledge-discovery-in-databases process to offer a multilayered view of AgNPs toxicity and translate our research from cell-based phenomenological observations to further in vitro and in vivo mechanistic explorations.Results: Cell viability assessment results was used to create a tree model for predicting toxicity evoked by four AgNP types: SCS, LCS, SAS, and LAS. This model ranked toxicity-relevant parameters in the order: dose > cell type > AgNP type ≥ exposure time. As suggested by the model, we chose a less responsive cell line to conduct further investigations. LCS among others was more capable of comprising viability of this cell line and could trigger higher levels of apoptosis and autophagy at a subcytotoxic dose. Even though at a cytotoxic dose, it was yet unable to evoke necrosis. Longer exposure to a noncytotoxic dose of LCS induced G2/M cell cycle arrest and senescence rather than eliciting apoptosis and autophagy. After a single intraperitoneal injection, SCS was found to be more toxic to mice than SAS, both of which could be deposited in various target organs (e.g., spleen, liver, and kidneys). Morphological observation, together with serum biochemical and histological analyses, indicated that AgNPs could produce pancreatic toxicity, apart from leading to hepatic inflammation. Conclusions: Our integrated in vitro, in silico, and in vivo study demonstrated that AgNPs could exert toxicity in dose-, cell/organ type- and particle type-dependent manners. More importantly, a single injection of lethal-dose AgNPs (i.e., SCS and SAS) could incur severe damage to pancreas and raise blood glucose levels at the early phase of exposure.

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