In-vivo Antimalarial Activity Research Articles

Phytochemical Analysis and In Vivo Antimalarial Activities of Ethyl Acetate Fraction of Spilanthes filicaulis on Mice Subjected to Plasmodium berghei.

Background and Objectives: Malaria airs a life-threatening risk in Tropical African countries, stemming from infection by Plasmodium species. This region is richly endowed by nature with a wealth of diverse and largely unexplored plants that hold the potential for managing this protozoan parasite. The currently accessible over-the-counter drugs for disease management often present affordability challenges for the average person, exacerbated by the parasite's increasing resistance to them. This study investigated the phytoconstituents present in the ethyl acetate fraction of Spilanthes filicaulis (EFSF) and explored the antimalarial effects of EFSF on mice infected with Plasmodium berghei. Methods: Standard methods and gas chromatography-mass spectrometry (GC-MS) were used to identify phytoconstituents. Chloroquine phosphate-sensitive P. berghei (NK-65) was intraperitoneally inoculated into Swiss mice. The invivo antimalarial activity of EFSF was assessed at dose levels of 250, 500, and 750 mg/kg, using 4-day suppressive and curative antimalarial models. Parameters evaluated in the inoculated mice included rectal temperature (RT), body weight (BW), packed cell volume (PCV), level of parasitemia, and mean survival time (MST). Results: Steroids, alkaloids, flavonoids, tannins, saponins, terpenoids, and cardiac glycosides were the identified phytochemicals present in EFSF, and GC-MS alongside reveals the presence of 20 bioactive compounds predominantly fatty acids and alcohol esters. Significant prevention of reductions in RT, BW, and PCV was observed in the EFSF-treated groups dose dependently relative to the untreated group. In addition, EFSF-treated groups significantly (p < 0.05) suppressed parasitemia and exhibited chemosuppression of 79.46% and 77.38% in 4-day suppressive, whereas suppression of 59.74% and 58.66% in curative treatment, respectively, at 500 and 750 mg/kg thus consequently extending the MST of infected treated mice compared with the untreated group. Interpretation and Conclusion: Put together, the EFSF exhibited enhanced antimalarial efficacy against mice infected with P. berghei thus affirming that plants still maintain lead way as a potential source of novel antimalarial remedies.

Cu-catalyzed click reaction in synthesis of eugenol derivatives as potent antimalarial agents

Eugenol(1), a terpenoid found in Ocimum, has various biological activities. The present study aims at extraction, isolation of the plant secondary metabolite eugenol (1), it’s derivatisation and structure identification as bioactive molecules. Synthesis and antiplasmodial activity (in-vitro and in-vivo), of a series of fourteen novel eugenol-based 1,2,3-triazole derivatives was done in the present study. Derivatives 5a–5n showed good antimalarial activity against the strain Plasmodium falciparum NF54. Derivative 5 m, IC50 at 2.85 µM was found to be several times better than its precursor 1 (106.82 µM) whereas the derivative 5n showed three fold better activity than compound 1, in vitro. The structure-activity relationship of the synthesised compounds indicated that the presence of triazole ring in eugenol analogues is responsible for their good activity. Compound 5m, was further evaluated for in-vivo antimalarial activity which showed about 79% parasitemia suppression. It is the first report on antimalarial activity of triazole eugenol derivatives.

In-Vivo Anti-Malarial Activity of 80% Methanol Leaf Extract of Croton Dichogamus Pax and Ehretia Cymosa Thonn in Plasmodium Berghei Infected Mice.

Malaria is causing high mortality and morbidity due to Plasmodium's resistance to currently available anti-malarial drugs and mosquito's resistance to insecticides. Thus, there is a critical need to search for novel anti-malarial drugs from natural sources. Therefore, this study investigated in vivo antimalarial activities of two Ethiopian medicinal plants, Croton dichogamus Pax and Ehretia cymosa Thonn, in Plasmodium berghei infected Swiss albino mice. Soxhlet extraction method using 80% methanol as a solvent was used to prepare crude extracts of the two plants. Acute oral toxicity and 4-day suppressive in vivo antimalarial activity tests were performed on healthy female mice and P. berghei infected male mice, respectively. Antimalarial activity of the crude extracts at doses of 100, 200, and 400 mg/kg and the standard drug, chloroquine were used to assesse in Plasmodium berghei infected Swiss albino mice. Parasitemia level, packed cell volume, body weight, and rectal temperature of the mice were determined before infection (day 0) and after treatment (day 4). Survival time was determined by recording the date on which the mice died, considering the date of infection as day 0. The recorded data were analyzed using ANOVA and SPSS version 24. The result of the acute toxicity study revealed that the crude extracts were non-toxic at doses up to 2 g/kg. The extract of E. cymosa suppressed parasitemia level by 66.28, 63.44 and 63.14% at 400, 200, and 100mg/kg, levels while C. dichogamus extract suppressed parasitemia level by 45.29% at a dose of 400mg/kg. The remaining two dose levels of C.dichogamus extract suppressed parasitemia level by < 30%. C. dichogamus and E. cymosa showed anti-plasmodial activities. E. cymosa exhibited a more pronounced anti-plasmodial effect than C. dichogamus. The activities of both plants observed in this study support their traditional use as antimalarial drugs. Further studies on these plants using solvent fractions are required to identify their active ingredients.

SYNTHESIS AND ANTIMALARIAL EVALUATION OF 1-(2,4- DIMETHOXYPHENYL)-3-(4-TRIFLUORO METHYL-PHENYL) PROPAN-2-ENE-1- ONE

Malaria is one of the most serious health problems worldwide and Its treatment has been compromised by drug resistance. Chalcones represent an important chemical scaffold with promising antimalarial activity. A chalcone derivative; 1(2,4dimethoxyphenyl)-3-(4-trifluoro methyl-phenyl) propan-2-ene-1-one (Compound P21) was synthesized by modified ClaisenSchmidt condensation reaction. The structure of compound P21 was established using Fourier transform infrared (FT-IR), proton and carbon-13 nuclear magnetic resonance (NMR) spectroscopy, and also mass spectrometry (MS). The compound was screened for in-vivo antimalarial activity in mice infected with P berghii parasite, using curative model. Compound P21 displayed appreciable activity (66% parasitaemia suppression) comparable to that of chloroquine (5 mg kg-1) at a dose of 175mg kg-1 in the curative test (p&lt;0.05). The present finding suggests that compound P21 is a promising antimalarial compound and is a candidate for further optimization and evaluation.

Nanoemulsion preconcentrate of a pentacyclic triterpene for improved oral efficacy: Formulation design and in-vivo antimalarial activity

In order to develop new lead from plant, natural product drug discovery is one of the popular choices which deal numerous unprecedented challenges. Lupeol, a monohydroxylated pentacyclic triterpenoid is abundantly distributed in the plants across genus in varying amount and posses antimalarial potential. However, the therapeutic potential of pentacyclic triterpenes is still under-exploited due to their low intestinal absorption. In the present study, a nanoemulsion preconcentrate (NPs) of lupeol with oil phase and ion surfactants was prepared and evaluated for antimalarial action. Lupeol was isolated and characterized from aerial parts of Stereospermum suaveolens DC. Oil phase comprising caprylic acid: oleic acid (2:1) and Smix (surfactant and co-surfactant) was used to develop a colloidal drug carrier following low energy nanoemulsion formation method. The Smix was optimized using tween 20 and transcutol HP (Km 2:1). Optimization of nanoemulsion was achieved in terms of thermodynamic stability, phase behaviour, globule size, polydispersity, rate of drug release, and high solubility without variable absorption for stable nanoemulsion. Developed NPs was investigated for in-vivo antimalarial efficacy. Improved efficacy was observed with a half dose of lupeol in nanoemulsion which attributed to a significant increase in blood glucose and haemoglobin level as compared with vehicle-treated infected mice. The present study is demonstrating that optimized nanoemulsion preconcentrate could be applied as a drug carrier for effective pentacyclic triterpene delivery and improved therapeutic action.

In-vitro and in-vivo antimalarial activity of caffeic acid and some of its derivatives

To explore the in-vitro and in-vivo antimalarial potential of caffeic acid and derivatives. Two common phenolic acids (caffeic acid and chlorogenic acid) were evaluated for in-vitro and in-vivo antiplasmodial activity in comparison with some semi-synthetic derivatives that were synthesized. An in-vitro assay based on plasmodial lactate dehydrogenase activity, and the classical in-vivo 5-day suppressive test from Peters on an artemisinin-resistant Plasmodium berghei strain was used. Parasitic stage sensitivity to ethyl caffeate was determined in this work. Phenolic acid esters derivatives showed better antiplasmodial activity than corresponding phenolic acids. The derivative with the highest in-vitro activity being caffeic acid ethyl ester, exhibiting an IC50 =21.9±9.4μm. Ethyl caffeate and methyl caffeate were then evaluated for antimalarial activity invivo and ethyl caffeate showed a growth inhibition of 55% at 100mg/kg. Finally, it seems that ethyl caffeate blocks the growth of young parasitic forms. Our study provides evidence for an antimalarial potential of caffeic acid derivatives which are common in several medicinal plants traditionally used against malaria. It also demonstrates the possibility to use such derivatives in the treatment of malaria.

Evaluation of the Antimalarial Effect of Ferulago angulata (Schlecht.) Boiss. Extract and Suberosin Epoxide Against Plasmodium berghei in Comparison with Chloroquine Using in-vivo Test.

Resistance to most antimalarial drugs has encouraged the development of novel drugs. An alternative source for discovering such drugs is natural products. Some Ferulago species are used in folk medicine for their sedative, tonic and anti-parasitic effects. Besides, coumarins isolated from this genus found to have in vitro anti-leishmanicidal effect. The present study is aimed to evaluate the in-vivo antimalarial activity of Ferulago angulata (Schlecht.) Boiss. extract and suberosin epoxide, using suarian mice. A rodent malaria parasite, Plasmodium berghei was used to inoculate healthy male Swiss Albino mice of age 6-8 weeks and weight 23-27 g. Hydro-alcoholic extract of F. angulata (20, 100, 300, 600 mg/Kg) and suberosin epoxide suspension (10, 30, 50, 100 mg/Kg) were administered subcutaneously. Parameters including percentage of parasitemia, suppression of parasitemia and mean survival time were determined using standard test such as peter٬s. Chemo-protective effects were exerted by the crude extract and suberosin epoxide. Maximum effect was observed with the larger doses of the crude extract and suberosin epoxide. Suberosin epoxide increased the survival time compared to chloroquine. However, the results of this study indicate that the plant has a promising anti-plasmodial activity against plasmodium berghei. Thus, it could be considered as a potential source of new antimalarial agents. Suberosin epoxide at the dose of 100 mg/Kg possesses relatively significant antimalarial effect. Chemical derivatization of the parent compound or preparation of the modified formulation is required to improve its systemic bioavailability.

In-vivo antimalarial activity of aqueous leaf and bark extracts of Trema orientalis against Plasmodium berghei in mice.

The control of malaria relies on the use of chemical antimalarial, but the development of resistance necessitates research into alternatives. Trema orientalis (L.) Blume is used in Nigerian folklore medicine for the treatment of malaria. This study investigates the in vivo antiplasmodial activity of aqueous leaf and bark extracts of T. orientalis in rodent model. Swiss Albino mice weighing 23-27g were intraperitoneally infected with Plasmodium berghei. The lethal dose in mice was estimated to be greater than 5000mg/kg based on toxicity signs and death. Aqueous crude leaf and bark extracts were administered at 400, 800 and 1600mg/kg. Chloroquine was used as positive control while the negative control was treated with distilled water. Parasitemia, parasite inhibition, body weight and packed cell volume (PCV) were determined. The parasite inhibition of the leaf extracts at 400, 800 and 1600mg/kg was 51.55, 62.78 and 76.08% while that of the bark extract was 44.3, 65.82 and 74.23% respectively. The percentage parasitemia of the leaf extract at 400, 800 and 1600mg/kg decreased by 45.0, 70.3 and 74.7% while that of the bark decreased by 37.4, 53.0 and 52.0% respectively. The PCV of mice treated with 400, 800 and 1600mg/kg leaf extract were 48.85, 49.88 and 50.99% while that of the bark extract was 49.38, 48.88 and 51.94% respectively. The results indicate that the plant has a promising antiplasmodial activity against P. berghei, which validates its folkloric use.

Evaluation of In-vivo Antimalarial Activity of Methanol Leaf Extract of Glyphaea brevis in Plasmodium berghei-Infected Mice

Purpose: To evaluate the in-vivo antimalarial activity of the methanol extract of the leaves of Glyphaea brevis in Plasmodium berghei infected mice.Methods: The phytochemical profile of ethylacetate, n-butanol, and residual aqueous fractions of the methanol extract of G. brevis were determined using standard procedures. Mice, weighing between 15 - 30 g, were used for this study. Plasmodium berghei infected blood (0.2 ml) was used to infect each of 55 mice (5 in 11 groups) intraperitoneally. Animals in the infected groups were treated orally with varying doses (200, 300 and 400 mg/kg body weight) of the ethylacetate, n-butanol and residual aqueous fractions daily, using artemisinin (5 mg/kg body weight per day) as standard drug, over a period of four days. The non-infected (normal control, n = 5) received distilled water (0.2 ml) while the infected control group (n = 5) was administered 0.2 ml normal saline. The suppressive antiplasmodial properties of the fractions as well as the serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were determined.Results: Alkaloids, carbohydrates, cardiac glycosides, flavonoids, saponins, tannins, steroids and triterpenes were present in the extract fractions. The suppressive antiplasmodial activity of n-butanol, residual aqueous portion and ethylacetate fractions was 76.64, 73.25 and 72.99 %, respectively, while that of artemisinin was 86.13 %. The serum concentrations of AST, ALT, and ALP in the infected control group were significantly higher (p &lt; 0.05) than those of the treated malaria-infected groups treated with the three fractions.Conclusion: Glyphaea brevis possesses significant antiplasmodial properties and could be a source of lead molecules for the development of new antimalarial agents.Keywords: Antimalarial, Glyphaea brevis, Plasmodium berghei, Artemisinin

Submicron oil-in-water emulsion formulations for mefloquine and halofantrine: effect of electric-charge inducers on antimalarial activity in mice.

Stearylamine, oleic acid, phosphatidylserine and dicetylphosphate have been studied to determine their capacity to induce electric charge on non-ionic submicron emulsions containing halofantrine and mefloquine. The in-vivo antimalarial activity of drug-loaded emulsions, evaluated in mice, was affected by the nature of the additives used. In particular, the electric-charge inducers markedly affected the pharmacological activity of mefloquine, but not of halofantrine. After subcutaneous administration ED50 values (the doses affording 50% protection) were 3 and 15 mg kg(-1), respectively, for halofantrine and mefloquine emulsions without charge inducers. The mefloquine-loaded emulsions with charge inducers were active at 10 mg kg(-1) for dicetylphosphate, 17 mg kg(-1) for phosphatidylserine, 23 mg kg(-1) for oleic acid and 27 mg kg(-1) for stearylamine, again after subcutaneous administration. This work has enabled the formulation of stable emulsions, incorporating drugs with high antimalarial activity, which are proposed for parenteral delivery of these fairly soluble drugs.

Recent developments in naturally derived antimalarials: cryptolepine analogues

Increasing resistance of Plasmodium falciparum to commonly used antimalarial drugs has made the need for new agents increasingly urgent. In this paper, the potential of cryptolepine, an alkaloid from the West African shrub Cryptolepis sanguinolenta, as a lead towards new antimalarial agents is discussed. Several cryptolepine analogues have been synthesized that have promising in-vitro and in-vivo antimalarial activity. Studies on the antimalarial modes of action of these analogues indicate that they may have different or additional modes of action to the parent compound. Elucidation of the mode of action may facilitate the development of more potent antimalarial cryptolepine analogues.

In-vivo antimalarial activity of some oxygenated xanthones.

A series of oxygenated xanthones was prepared so that the antimalarial activity of each compound could be evaluated in vivo, using 4-day suppressive assays against Plasmodium berghei ANKA in BALB/c mice. When given in a dose of 20 mg/kg.day for 4 days, most of the compounds produced significant chemosuppression of parasitaemia. The most active compound was 1,3,6,8-tetrahydroxyxanthone, which reduced the percentage of erythrocytes infected by 70.5%, followed by norlichexanthone (44.3%) and its isomer, 1,3,8-trihydroxy-6-methylxanthone (37.0%). Whereas di-C-allyl-dihydroxyxanthone showed lower but still notable activity (33.4%), 1,3-dihydroxyxanthone was much less active (15.1%). This appears to be the first demonstration of the antimalarial activity of some hydroxyxanthones in vivo.

Geraniol-derived 1,2,4-trioxanes with potent in-vivo antimalarial activity.

Geraniol, an abundantly available naturally occurring allylic alcohol, has been used as a starting material to prepare a series of 6-[alpha-(3'-aryl-3'-hydroxypropyl)vinyl]-1,2,4-trioxanes. Some of these novel trioxanes have shown very promising antimalarial activity against multi-drug resistant Plasmodium yoelii in mice by both intramuscular (im) and oral routes.