In vivo antimalarial activity and pharmacokinetics of artelinic acid-choline derivative liposomes in rodents

Parasitology ◽  
2019 ◽  
Vol 147 (1) ◽  
pp. 58-64
Author(s):  
Shuai Duan ◽  
Ruili Wang ◽  
Rongrong Wang ◽  
Jiaqi Tang ◽  
Xiaoyang Xiao ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antimalarial Activity ◽  
Positive Control ◽  
Plasmodium Yoelii ◽  
Esterification Reaction ◽  
Therapeutic Effects ◽  
Control Groups ◽  
Time Curve ◽  
Survival Fraction

AbstractIt is urgent to develop new antimalarial drugs with good therapeutic effects to address the emergence of drug resistance. Here, the artelinic acid-choline derivative (AD) was synthesized by dehydration reaction and esterification reaction, aimed to avoid the emergence of drug resistance by synergistic effect of artemisinins and choline derivative, which could compete with choline for rate-limiting enzymes in the phosphatidylcholine (PC) biosynthetic pathway. AD was formulated into liposomes (ADLs) by the thin-film hydration method. Efficacy of ADLs was evaluated by Peters 4-day suppression test. The suppression percentage against Plasmodium yoelii BY265 (PyBY265) in ADLs group was higher than those of positive control groups (dihydroartemisinin liposomes, P < 0.05) and other control groups (P ⩽ 0.05) at the doses of 4.4, 8.8, 17.6 µmol (kg·d)−1, respectively. The negative conversion fraction, recrudescence fraction and survival fraction of ADLs group were superior to other control groups. Pharmacokinetics in rats after intravenous injection suggested that ADLs exhibited higher exposure levels (indexed by area under concentration-time curve) than that of AD solution, artelinic acid liposomes or artelinic acid solution (P < 0.01). Taken together, ADLs exhibited promising antimalarial efficacy and pharmacokinetic characteristics.

scholarly journals Therapeutic effects of sesamolin on leukemia induced by WEHI-3B in model mice

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Senthil Nagarajan ◽  
Jae Kwon Lee
Keyword(s):  
Nk Cell ◽  
Neoplastic Cell ◽  
Positive Control ◽  
Cytolytic Activity ◽  
Leukemic Cells ◽  
Therapeutic Effects ◽  
Control Drug ◽  
Lysis Activity

AbstractSesamolin is one of the lignans derived from sesame oil. It has demonstrated significant antioxidant, anti-aging, and anti-mutagenic properties. It also reportedly augments natural killer (NK) cell lysis activity. We previously reported that sesamolin also exerts anticancer effects in vitro and induces enhanced NK cell cytolytic activity against tumor cells. Herein, we aimed to determine the mechanism by which sesamolin prevents and retards tumorigenesis in BALB/c mouse models of leukemia induced by murine (BALB/c) myelomonocytic leukemia WEHI-3B cells. Banded neutrophils, myeloblasts, and monocytic leukemic cells were more abundant in the leukemia model than in normal mice. Sesamolin decreased the number of leukemic cells by almost 60% in the leukemia model mice in vivo; additionally, sesamolin and the positive control drug, vinblastine, similarly hindered neoplastic cell proliferation. Spleen samples were ~ 4.5-fold heavier in leukemic mice than those obtained from normal mice, whereas spleen samples obtained from leukemic mice treated with sesamolin had a similar weight to those of normal mice. Moreover, sesamolin induced a twofold increase in the cytotoxic activity of leukemic mouse NK cells against WEHI-3B cells. These results indicated that sesamolin exerts anti-leukemic effects in vivo.

scholarly journals Medicinal Plants Used for Malaria Treatment in Gamba Village, North Region of Cameroon: Ethnopharmacological Survey; In Vivo Antimalarial Activity of Aqueous Extracts of Khaya Senegalensis Bark.

2021 ◽  
Author(s):  
Davy-Hyacinthe Anguechia Gouissi ◽  
Roselyne Teponging Nzangue ◽  
Josue Haskandi Kalaza ◽  
Willy Pabo ◽  
Siméon Pierre Fodouop Chegaing
Keyword(s):  
Medicinal Plants ◽  
Traditional Medicine ◽  
Aqueous Extract ◽  
Antimalarial Activity ◽  
Traditional Healers ◽  
Positive Control ◽  
Control Group ◽  
Aqueous Extracts ◽  
Khaya Senegalensis

Abstract Background: In traditional medicine, the floral diversity permits the inhabitants of North Cameroon to use a great number of plants to fight against Malaria. The aim of this study was to identify plants used in traditional medicine to treat malaria, and to verify the scientific basis for the use of one of these plants in the locality of Gamba.Methods: An Ethnopharmacological survey was carried out on 15 traditional healers. We collected data on use of medicinal plants using questionnaires. Then in-vivo antimalarial activity of the decoctioned and macerated aqueous extracts of khaya senegalensis trunk bark was evaluated. The 4-day suppressive peters test was realised on mus musculus swiss albino mice. On day one, mice were infected with 107 plasmodium berghei parasitized red blood cells through intra-peritoneal inoculation. 2 hours after infestation, mice in batches of 6 were treated orally at a dose of 75, 150.300 mg/Kg for macerated aqueous extract and 65, 120.260 mg/Kg for decoctioned extract daily during 3 days at an administration volume of 10 ml/Kg. An extract was considered (% reduction): Highly active (between 100-90 %); moderate (between 90-50 %); weak (between 50-10 %); Inactive (between 0 %). P-values <0.05 were considered statistically significant.Results: A total of 18 plant species belonging to 12 families were identified for the preparation of 12 recipes. The decocted aqueous extract of khaya senegalensis showed moderate anti-plasmodial activity (% reduction = 52.46%) at the highest dose of 260 mg/kg with p<0.001 compared to the positive control group. The aqueous macerate at doses of 150 and 300mg/kg gave respectively a percentage reduction of parasitaemia of 59.42% and 71.80% and also showed moderate anti-plasmodial activity; with p<0.001 between the different extracts and the positive control (99.18%).Conclusion: In conclusion, extracts of khaya senegalensis showed moderate anti-plasmodial activity. It would therefore be necessary to evaluate the anti-malarial activity in-vivo and the toxicity of the aqueous extracts macerated using other solvents and also test the other plants listed.

scholarly journals Computational Chemogenomics Drug Repositioning Strategy Enables the Discovery of Epirubicin as a New Repurposed Hit for Plasmodium falciparum and P. vivax

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Letícia Tiburcio Ferreira ◽  
Juliana Rodrigues ◽  
Gustavo Capatti Cassiano ◽  
Tatyana Almeida Tavella ◽  
Kaira Cristina Peralis Tomaz ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
In Silico ◽  
Antimalarial Activity ◽  
Drug Repositioning ◽  
Dna Gyrase ◽  
Plasmodium Yoelii ◽  
Computer Assisted ◽  
Content Type

ABSTRACT Widespread resistance against antimalarial drugs thwarts current efforts for controlling the disease and urges the discovery of new effective treatments. Drug repositioning is increasingly becoming an attractive strategy since it can reduce costs, risks, and time-to-market. Herein, we have used this strategy to identify novel antimalarial hits. We used a comparative in silico chemogenomics approach to select Plasmodium falciparum and Plasmodium vivax proteins as potential drug targets and analyzed them using a computer-assisted drug repositioning pipeline to identify approved drugs with potential antimalarial activity. Among the seven drugs identified as promising antimalarial candidates, the anthracycline epirubicin was selected for further experimental validation. Epirubicin was shown to be potent in vitro against sensitive and multidrug-resistant P. falciparum strains and P. vivax field isolates in the nanomolar range, as well as being effective against an in vivo murine model of Plasmodium yoelii. Transmission-blocking activity was observed for epirubicin in vitro and in vivo. Finally, using yeast-based haploinsufficiency chemical genomic profiling, we aimed to get insights into the mechanism of action of epirubicin. Beyond the target predicted in silico (a DNA gyrase in the apicoplast), functional assays suggested a GlcNac-1-P-transferase (GPT) enzyme as a potential target. Docking calculations predicted the binding mode of epirubicin with DNA gyrase and GPT proteins. Epirubicin is originally an antitumoral agent and presents associated toxicity. However, its antiplasmodial activity against not only P. falciparum but also P. vivax in different stages of the parasite life cycle supports the use of this drug as a scaffold for hit-to-lead optimization in malaria drug discovery.

scholarly journals In Vitro and In Vivo Anti-Salmonella Evaluation of Pectin Extracts and Hydrolysates from “Cas Mango” (Spondias dulcis)

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Denis Zofou ◽  
Golda Lum Shu ◽  
Josepha Foba-Tendo ◽  
Merveille Octavie Tabouguia ◽  
Jules-Clement N. Assob
Keyword(s):  
Multidrug Resistant ◽  
Positive Control ◽  
Resistant Bacteria ◽  
Therapeutic Effects ◽  
Diffusion Technique ◽  
Resistant Strains ◽  
Almost All ◽  
Broth Dilution

Background. The threat to human health posed by multidrug-resistant strains of Salmonella typhi (S. typhi) and Salmonella paratyphi (S. paratyphi) is of growing concern. Generally, there has been increasing resistance and even multidrug resistance to almost all classes of antibiotics. This has rendered treatment with antibiotics difficult and costly. The present study investigated the bioactivity of pectin and pectin hydrolysates derived from a local fruit, Spondias dulcis, against four strains of Salmonellae. Methods. Pectin was extracted from alcohol extractives-free peel by acidic hydrolysis at a temperature of 80°C for one hour at pH 2 and 4. The pectin was precipitated with 95% alcohol at an extract to alcohol ratio of 1:10 v/v. Antimicrobial activity was determined using agar well diffusion technique. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were determined using the broth dilution technique. An in vivo study was then carried out with the bioactive extracts against the most resistant bacteria strain, to fully establish the therapeutic effect of these extracts. Balb/C mice were used, and ciprofloxacin was the positive control antibiotic. The extracts were administered to mice at two doses, 5mg/Kg and 10mg/Kg. The efficacy of extracts in the treatment of typhoid was evaluated based on survival rate, change in body weight, and change in bacteria load. Results. Only one of the extracts (crude pectin pH 2.5) was active against all the Salmonellae by well diffusion, and the growth inhibition varied from 12mm to 15mm at100 μg/ml. Three of the extracts (crude pectin pH 2.5, pH 4, 12h hydrolysate, and pH 4, 1h hydrolysate) had MIC and MBC against all four Salmonellae strains with MIC ranging from 5.68 to 44.45 μg/ml and MBC from 11.36 to 44.45 μg/mL. Three treatments, namely, the pH4-12 hr, hydrolysate at 10mg/Kg and 5mg/Kg, and the pH4-1hr, hydrolysate at 10mg/Kg, had therapeutic effects against Salmonella infection in mice. Conclusion. The present study highlights the potential of pectin oligosaccharides as new source of anti-Salmonella drugs. Further investigations including exploration of mechanism of action of the most active pectin extracts/hydrolysates are envisaged.

scholarly journals Enhanced Antimalarial Activity by a Novel Artemether-Lumefantrine Lipid Emulsion for Parenteral Administration

2014 ◽  
Vol 58 (10) ◽  
pp. 5658-5665 ◽  
Author(s):  
Yufan Ma ◽  
Tingli Lu ◽  
Wen Zhao ◽  
Ying Wang ◽  
Ting Chen ◽  
...  
Keyword(s):  
Lipid Emulsion ◽  
Antimalarial Activity ◽  
Physical Stability ◽  
Aqueous Solubility ◽  
Positive Control ◽  
Parenteral Administration ◽  
Control Group ◽  
Content Type ◽  
Physical And Chemical

ABSTRACTArtemether and lumefantrine (also known as benflumetol) are difficult to formulate for parenteral administration because of their low aqueous solubility. Cremophor EL as an emulsion excipient has been shown to cause serious side effects. This study reports a method of preparation and the therapeutic efficacies of novel lipid emulsion (LE) delivery systems with artemether, lumefantrine, or artemether in combination with lumefantrine, for parenteral administration. Their physical and chemical stabilities were also evaluated. Furthermore, thein vivoantimalarial activities of the lipid emulsions developed were tested inPlasmodium berghei-infected mice. Artemether, lumefantrine, or artemether in combination with lumefantrine was encapsulated in an oil phase, and thein vivoperformance was assessed by comparison with artesunate for injection. It was found that the lumefantrine lipid emulsion (LUM-LE) and artemether-lumefantrine lipid emulsion (ARM-LUM-LE-3) (1:6) began to decrease the parasitemia levels after only 3 days, and the parasitemia inhibition was 90% at doses of 0.32 and 0.27 mg/kg, respectively, with immediate antimalarial effects greater than those of the positive-control group and constant antimalarial effects over 30 days. LUM-LE and ARM-LUM-LE-3 demonstrated the best performance in terms of chemical and physical stabilities and antiplasmodial efficacy, with a mean particle size of 150 nm, and they have many favorable properties for parenteral administration, such as biocompatibility, physical stability, and ease of preparation.

scholarly journals Combination of Calotropis gigantea Radix Extract and Artemisin as an Antimalarial Agent Against Plasmodium berghei

2016 ◽  
Vol 1 (1) ◽  
pp. 12
Author(s):  
Roihatul Muti’ah ◽  
Elok Kamilah Hayati ◽  
Asnal Fatati
Keyword(s):  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Positive Control ◽  
Negative Control ◽  
Calotropis Gigantea ◽  
Treatment Groups ◽  
Tukey Test ◽  
Bioactive Component ◽  
Phytochemical Compounds

<p><em>Calotropis gigantea</em> radix is one of plant which has bioactive component as antimalarial.The purpose of this research are to know antimalarial activity from combination of <em>Calotropis gigantea</em> radix extract and artemisin. The research consist of extraction of <em>Calotropis gigantea</em> radix was done with extraction maseration method. Extraction was performed by maseration with  80% ethanol solvent. Concentrated extract was <em>in vivo </em>antimalarial tested to animal model. Mice were peritoneal infected with 10<sup>6</sup><em>Plasmodium berghei</em> ANKA and divided into 5 treatment groups: negative control; positive control (artemisin of dose 4 mg/kgBW); combination of artemisin(1/4 dose of artemisin standar) and <em>Calotropis gigantea</em>in 3 doses: 0,1 mg/KgBW; 1 mg/KgBWand 10 mg/KgBW. Data of inhibition was analyzed using SPSS program with <em>Two Way </em>ANOVA Test dan continued with Tukey Test.</p><p class="DefaultCxSpFirst">The result shows that combination of <em>Calotropis gigantea</em> radix extract and artemisin with dose 10 mg/KgBB has higher antimalarial activity than control positive (artemisin). The value of parasite inhibition is 55,2% for dose 0.1 mg/KgBW ; 72,8% for dose 1 mg/KgBW ; 87,3% for dose 10 mg/KgBW and 56,06 mg/KgBW for control positive (artemisin). The phytochemical compounds in 80%  ethanol solvent extract are tannins and steroids.</p><div><p class="DefaultCxSpMiddle"> </p><p class="DefaultCxSpLast"><strong>Keywords</strong>: <em>Calotropis gigantea,</em><em>antimalaria, combination, artemisin, </em><em>Plasmodium berghei</em><strong></strong></p></div>

Investigation on the antimalarial properties of Plumeria alba Linn (apocynaceae) cultivated in Nigeria

2021 ◽  
Vol 25 (1) ◽  
pp. 34-42
Author(s):  
S.A. Adesida ◽  
S.A. Odediran ◽  
A.A. Elujoba
Keyword(s):  
Ethyl Acetate ◽  
Survival Time ◽  
Antimalarial Activity ◽  
Stem Bark ◽  
Positive Control ◽  
Bark Extract ◽  
Survival Times ◽  
Average Percentage ◽  
Effective Doses

Many of the African antimalarial ethno medicinal plants are good sources of promising antimalarial compounds. The stem bark of Plumeria alba Linn, was evaluated for in vivo chemosuppressive antimalarial activities in order to identify the most active solvent  fraction from which antimalarial constituents can be isolated. The stem-bark of Plumeria alba Linn, family Apocynaceae was   collected, air-dried, powdered, macerated in methanol and the extract concentrated in vacuo. The acute toxicity study was   performed on the extract using Lorke’s method. The extract was thereafter tested for chemosuppressive antiplasmodial activities against Plasmodium berghei berghei NK65- infected mice using Peter’s four-day test at doses 100-800 mg /kg with normal saline (0.2 ml) and chloroquine (10 mg/kg) as negative and positive control drugs respectively. The average percentage parasitaemia, percentage chemosuppression and effective doses (ED50 and ED90), the survival times and percentage survivors elicited in all the  mice were  determined as indices of antimalarial activity. The active extract was  subsequently partitioned successively into n-hexane, dichloromethane, ethyl acetate and butanol. The respective partitioned fractions with the aqueous phase were also tested as above at doses 0-80 mg/kg. All results were  subjected to statistical analysis using ANOVA with Student Newman Keul’s post hoc test. Crude extracts of P. alba gave considerable reduction of percentage parasitaemia up to 200 mg/kg. The percentage  chemosuppression at all doses, were significantly higher (p<0.05) than the negative but lower than the positive control with 200 mg/kg dose showing the highest activity of 65.88 %. The effective doses, ED50 and ED90 were  305.82±9.99 and 389.74± 9.60, respectively. The most active n-hexane partitioned fraction elicited a percentage chemosuppression of 67.75 and a significantly lower (p<0.05) ED50 and ED90 of 31.27±0.85 and 54.80±1.75 mg/kg. The butanol and ethyl acetate partitioned fractions gave significantly higher (p<0.05) survival time value than those of the crude extract, other partition fractions and the positive control, while the n-hexane, dichloromethane and the aqueous, just like chloroquine, gave high percentage survivors. The study concluded that Plumeria alba stem-bark extract was active as an antimalarial drug with its antiplasmodial and the survival time–enhancing activity concentrated in the n-hexane and ethyl acetate with butanol partitioned fractions respectively, thus confirming and justifying its ethnomedical application in malaria.

scholarly journals Antimalarial Activity of Small-Molecule Benzothiazole Hydrazones

2016 ◽  
Vol 60 (7) ◽  
pp. 4217-4228 ◽  
Author(s):  
Souvik Sarkar ◽  
Asim A. Siddiqui ◽  
Shubhra J. Saha ◽  
Rudranil De ◽  
Somnath Mazumder ◽  
...  
Keyword(s):  
Murine Model ◽  
Resistant Strain ◽  
Therapeutic Potential ◽  
Antimalarial Activity ◽  
Hematological Parameters ◽  
Plasmodium Yoelii ◽  
Multiple Drug ◽  
Content Type

ABSTRACTWe synthesized a new series of conjugated hydrazones that were found to be active against malaria parasitein vitro, as well asin vivoin a murine model. These hydrazones concentration-dependently chelated free iron and offered antimalarial activity. Upon screening of the synthesized hydrazones, compound 5f was found to be the most active iron chelator, as well as antiplasmodial. Compound 5f also interacted with free heme (KD[equilibrium dissociation constant] = 1.17 ± 0.8 μM), an iron-containing tetrapyrrole released after hemoglobin digestion by the parasite, and inhibited heme polymerization by parasite lysate. Structure-activity relationship studies indicated that a nitrogen- and sulfur-substituted five-membered aromatic ring present within the benzothiazole hydrazones might be responsible for their antimalarial activity. The dose-dependent antimalarial and heme polymerization inhibitory activities of the lead compound 5f were further validated by following [3H]hypoxanthine incorporation and hemozoin formation in parasite, respectively. It is worth mentioning that compound 5f exhibited antiplasmodial activityin vitroagainst a chloroquine/pyrimethamine-resistant strain ofPlasmodium falciparum(K1). We also evaluatedin vivoantimalarial activity of compound 5f in a murine model where a lethal multiple-drug-resistant strain ofPlasmodium yoeliiwas used to infect Swiss albino mice. Compound 5f significantly suppressed the growth of parasite, and the infected mice experienced longer life spans upon treatment with this compound. Duringin vitroandin vivotoxicity assays, compound 5f showed minimal alteration in biochemical and hematological parameters compared to control. In conclusion, we identified a new class of hydrazone with therapeutic potential against malaria.

Synthesis and antimalarial activity of novel bicyclic and tricyclic aza-peroxides

RSC Advances ◽  
2016 ◽  
Vol 6 (28) ◽  
pp. 23718-23725 ◽  
Author(s):  
Lalit Yadav ◽  
Mohit K. Tiwari ◽  
Bharti Rajesh Kumar Shyamlal ◽  
Manas Mathur ◽  
Ajit K. Swami ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Oral Route ◽  
Plasmodium Yoelii ◽  
Swiss Mice

Bicyclic and tricyclic aza-peroxides were synthesized and assessed for theirin vitroandin vivoantimalarial activities againstPlasmodium falciparum(3D7 strain) andPlasmodium yoelii nigeriensisin Swiss mice by an oral route, respectively.

scholarly journals In VivoAntimalarial Activity ofAnnona muricataLeaf Extract in Mice Infected withPlasmodium berghei

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Voravuth Somsak ◽  
Natsuda Polwiang ◽  
Sukanya Chachiyo
Keyword(s):  
Survival Time ◽  
Leaf Extract ◽  
Antimalarial Activity ◽  
Positive Control ◽  
Annona Muricata ◽  
The World ◽  
Aqueous Leaf Extract ◽  
New Compounds ◽  
Dose Dependent

Malaria is one of the most important infectious diseases in the world. The choice for the treatment is highly limited due to drug resistance. Hence, finding the new compounds to treat malaria is urgently needed. The present study was attempted to evaluate the antimalarial activity of theAnnona muricataaqueous leaf extract inPlasmodium bergheiinfected mice. Aqueous leaf extract ofA. muricatawas prepared and tested for acute toxicity in mice. For efficacy testin vivo, standard 4-day suppressive test was carried out. ICR mice were inoculated with 107parasitized erythrocytes ofP. bergheiANKA by intraperitoneal injection. The extracts (100, 500, and 1000 mg/kg) were then given orally by gavage once a day for 4 consecutive days. Parasitemia, percentage of inhibition, and packed cell volume were subsequently calculated. Chloroquine (10 mg/kg) was given to infected mice as positive control while untreated control was given only distilled water. It was found thatA. muricataaqueous leaf extract at doses of 100, 500, and 1000 mg/kg resulted in dose dependent parasitemia inhibition of 38.03%, 75.25%, and 85.61%, respectively. Survival time was prolonged in infected mice treated with the extract. Moreover, no mortality to mice was observed with this extract up to a dose of 4000 mg/kg. In conclusion, theA. muricataaqueous leaf extract exerted significant antimalarial activity with no toxicity and prolonged survival time. Therefore, this extract might contain potential lead molecule for the development of a new drug for malaria treatment.

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