Suppression Of Parasitemia Research Articles

THE EFFICACY OF THE AQUEOUS EXTRACT OF ADANSONIA DIGITATA AGAINST PLASMODIUM BERGHEI INFECTION IN MICE

The prevalence of malaria remains a significant threat in Sub-Saharan Africa. The occurrence of drug-resistant strains of Plasmodium in Nigeria underscores the urgent need for novel antimalarial medications. This research aims to assess the effectiveness of Adansonia digitata fruit pod extract against Plasmodium berghei infection in mice; determining the oral median lethal dose (LD50) and identifying phytochemical components using Lorke's and Evan's methodologies. The extract was assessed for its antiplasmodial activities against P. berghei-berghei in two murine malaria replicas using both suppressive and curative assays. Statistical analysis was conducted using one-way ANOVA. The LD50 of the extract through oral administration exceeded 5000 mg/kg. The extract contains alkaloids, saponins, flavonoids, phenols, tannins, and anthraquinones. The aqueous fruit pulp extract of A. digitata, when administered at 250, 500, and 1000 mg/kg of doses, exhibited a dose-dependent suppression of parasitemia by 25.70%, 42.57%, and 49.39% respectively compared to the control group, parasitaemia clearance rates was 31.76%, 43.34%, and 56.65% respectively. The parasitaemia clearance with a dosage of 1000 mg/kg was found to be statistically significant (p < 0.05).The reference drug (Chloroquine) administering a dosage of 5 mg/kg yielded a significant result (p < 0.05) parasitaemia clearance of 74.76%. Analysis of the Packed Cell Volume (PCV) levels revealed that those treated with the aqueous fruit pulp extracts of A. digitata at doses of 250, 500, and 1000 mg/kg maintained normal PCV values throughout suppressive and curative experiments. However, the PCV in the control groups was markedly diminished (p < 0.05) after both trials.

Exploring the potential antimalarial properties, safety profile, and phytochemical composition of Mesua ferrea Linn.

The increased resistance of Plasmodium falciparum to artemisinin and its partner drugs poses a serious challenge to global malaria control and elimination programs. This study aimed to investigate the therapeutic potential of Mesua ferrea Linn., a medicinal plant, as a source for novel antimalarial compounds. In this study, we conducted in vitro assays to evaluate the antimalarial activity and cytotoxicity of crude extracts derived from M. ferrea L. leaves and branches. Subsequently, the most promising extracts were subjected to assessments of their antimalarial efficacy and acute oral toxicity tests in mouse models. Furthermore, selected crude extracts underwent gas chromatography-mass spectrometry (GC-MS) analysis to identify their phytochemical compositions. Our findings revealed that the ethanolic extract of M. ferrea L. branches (EMFB) exhibited high antimalarial activity, with an IC50 value of 4.54 μg/mL, closely followed by the ethanolic extract of M. ferrea L. leaves (EMFL), with an IC50 value of 6.76 μg/mL. Conversely, the aqueous extracts of M. ferrea L. branches (AMFB) and leaves (AMFL) exhibited weak and inactive activity, respectively. The selected extracts, EMFB and EMFL, demonstrated significant dose-dependent parasitemia suppression, reaching a maximum of 62.61% and 54.48% at 600 mg/kg body weight, respectively. Furthermore, the acute oral toxicity test indicated no observable toxicity at a dosage of 2,000 mg/kg body weight for both extracts. GC-MS analysis revealed abundant compounds in the EMFB, such as oleamide, cis-β-farnesene, alloaromadendrene, physcion, palmitic acid, 5-hydroxymethylfurfural, and 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-, while the EMFL contained friedelin, friedelinol, betulin, β-caryophyllene, oleamide, and 5-hydroxymethylfurfural. Notably, both extracts shared several phytochemical compounds, including 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-, 5-hydroxymethylfurfural, α-copaene, cyperene, β-caryophyllene, alloaromadendrene, palmitic acid, ethyl palmitate, and oleamide. Additionally, further study is needed to isolate and characterize these bioactive compounds from M. ferrea L. leaves and branches for their potential utilization as scaffolds in the development of novel antimalarial drugs.

Antioxidant and Antiplasmodial Potentials of Methanol Bark Extract of <i>Entada africana </i>Via <i>in Vitro</i> Approaches

<i>Plasmodium </i>parasites, which cause malaria, continue to pose a serious threat to global health, necessitating the continuous search for novel antimalarial agents. Oxidative stress has also been linked to the pathophysiology of malaria. <i>Entada africana</i> is a plant known for its ethnomedicinal uses in treating various ailments associated with inflammation including malaria. This study aimed at evaluating the antiplasmodial and antioxidant potentials of methanol bark extract from <i>Entada africana </i>(MBEEA). <i>In vitro </i>approaches were adopted for the study.<i> Plasmodium falciparum-</i>infected erythrocyte samples were cultured in Roswell Park Memorial Institute (RPMI) 1640 media under anaerobic conditions for 72 hours. Eighteen test tubes were labeled and grouped into three replicates per group. Group I (untreated), Group II, and III were treated with chloroquine (CQ) and artemether (AR) at a concentration of 5 mg/dL. Group IV, V, and VI were treated with the extract at respective concentrations of 5 mg/dL, 10 mg/dL, and 20 mg/dL for 72 hours. The parasitemia count and the percentage parasitemia inhibition were determined by microscopic examination of Giemsa-stained smears. The antioxidant potential of the extract was assessed using <i>in vitro</i> assays, including superoxide radical scavenging activity (SRSA), hydroxyl radical scavenging activity (HRSA), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP). Microscopic examination of the treated samples revealed varying degrees of parasitemia inhibition. Group II and III treated with CQ and AR demonstrated a considerable reduction in parasitemia count with percentage inhibition of 100% and 83% respectively. The <i>E. africana</i> extract showed a concentration-dependent effect on parasitemia count. At 5 mg/dL, the extract exhibited 50% parasitemia inhibition, which increased to 100% at 10 mg/dL, and 20 mg/dL respectively. The MBEEA demonstrated significant <i>in vitro </i>antioxidant activities by scavenging DPPH, SRSA, and hydroxyl radical compared to the standard antioxidant (ascorbic acid). MBEEA thus exhibit potent antioxidant and antiplasmodial properties. This plant is therefore offers to be a promising medicinal plant in the treatment of malaria, hence it is recommended as potent antiplasmodial plant usable for treating malaria.

Aktivitas Antimalaria Ekstrak Sargassum Duplicatum terhadap Plasmodium Berghei Strain ANKA Secara in Vivo

Malaria is a parasitic infection disease caused by Plasmodium and is a global health issue. The search for new antimalarial drugs from natural sources, such as plants, is ongoing to find effective alternatives. Sargassum duplicatum, a brown seaweed, has been known to possess various biological activities; however, its antimalarial potential has not been thoroughly explored. This study aims to evaluate the antimalarial activity of S. duplicatum extract against Plasmodium berghei strain ANKA in vivo in mice. This is an experimental study. A total of 16 mice were divided into 4 groups: a positive control group and groups infected with P. berghei and treated with S. duplicatum extract at doses of 10, 100, and 200 mg/g body weight. Antimalarial activity was measured based on parasitemia levels, percent inhibition, and ED50 values. Parasitemia measurements were taken from day 0 to day 6 after treatment. The results showed that S. duplicatum extract inhibited the growth of P. berghei with parasitemia inhibition percentages of 65.32% at a dose of 10 mg/g body weight, 65.92% at a dose of 100 mg/g body weight, and 86.61% at a dose of 200 mg/g body weight. The ED50 value of S. duplicatum extract was 2.770 mg/kg body weight in mice. The low ED50 value indicates the extract’s potential as a promising antimalarial drug candidate.

Antimalarial efficacy test of the aqueous crude leaf extract of Coriandrum sativum Linn.: an in vivo multiple model experimental study in mice infected with Plasmodium berghei

BackgroundMalaria continues to wreak havoc on the well-being of the community. Resistant parasites are jeopardizing the treatment. This is a wake-up call for better medications. Folk plants are the key starting point for antimalarial drug discovery. After crushing and mixing the leaves of Coriandrum sativum with water, one cup of tea is drunk daily for a duration of three to five days as a remedy for malaria by local folks in Ethiopia. Additionally, in vitro experiments conducted on the plant leaf extract elsewhere have also demonstrated the plant’s malaria parasite inhibitory effect. There has been no pharmacologic research to assert this endowment in animals, though. This experiment was aimed at evaluating the antimalarial efficacy of C. sativum in Plasmodium berghei infected mice.MethodsThe plant's leaf was extracted using maceration with distilled water. The extract was examined for potential acute toxicity. An evaluation of secondary phytoconstituents was done. Standard antimalarial screening models (prophylactic, chemosuppressive, curative tests) were utilized to assess the antiplasmodial effect. In each test, thirty mice were organized into groups of five. To the three categories, the test substance was given at doses of 100, 200 and 400 mg/kg/day before or after the commencement of P. berghei infection. Positive and negative control mice were provided Chloroquine and distilled water, respectively. Rectal temperature, parasitemia, body weight, survival time and packed cell volume were ultimately assessed. Analysis of the data was performed using Statistical Package for Social Sciences.ResultsNo toxicity was manifested in mice. The extract demonstrated a significant inhibition of parasitemia (p < 0.05) in all the models. The inhibition of parasite load was highest with the upper dose in the suppressive test (82.74%) followed by the curative procedure (78.49%). Likewise, inhibition of hypothermia, weight loss hampering, improved survival and protection against hemolysis were elicited by the extract.ConclusionsThe results of our experimental study revealed that the aqueous crude leaf extract of C. sativum exhibits significant antimalarial efficacy in multiple in vivo models involving mice infected with P. berghei. Given this promising therapeutic attribute, in depth investigation on the plant is recommended.

Development, characterization, and evaluation of withaferin-A and artesunate-loaded pH-responsive acetal-dextran polymeric nanoparticles for the management of malaria

Artemisinin and its derivatives have been commonly used to treat malaria. However, the emergence of resistance against artemisinin derivatives has posed a critical challenge in malaria management. In the present study, we have proposed a combinatorial approach, utilizing pH-responsive acetal-dextran nanoparticles (Ac-Dex NPs) as carriers for the delivery of withaferin-A (WS-3) and artesunate (Art) to improve treatment efficacy of malaria. The optimized WS-3 and Art Ac-Dex NPs demonstrated enhanced pH-responsive release profiles under parasitophorous mimetic conditions (pH 5.5). Computational molecular modeling reveals that Ac-Dex's polymeric backbone strongly interacts with merozoite surface protein-1 (MSP-1), preventing erythrocyte invasion. In-vitro antimalarial activity of drug-loaded Ac-Dex NPs reveals a 1–1.5-fold reduction in IC50 values compared to pure drug against the 3D7 strain of Plasmodium falciparum. Treatment with WS-3 Ac-Dex NPs (100 mg/kg) and Art Ac-Dex NPs (30 mg/kg) to Plasmodium berghei-infected mice resulted in 78.11 % and 100 % inhibition of parasitemia. Notably, the combination therapy comprised of Art and WS-3 Ac-Dex NPs achieved complete inhibition of parasitemia even at a half dose of Art, indicating the synergistic potential of the combinations. However, further investigations are necessary to confirm the safety and effectiveness of WS-3 and Art Ac-Dex NPs for their successful clinical implications.

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.

Unveiling the antimalarial properties of Terminalia ivorensis (A. Chev) stem bark aqueous extract: In vivo efficacy testing and in silico predictions

Due to the spreading resistance to antimalarial drugs, new therapeutics are urgently needed, preferably with novel modes of action. Extracts from Terminalia ivorensis have previously been shown to possess activity in vitro against multidrug-resistant and drug-sensitive strains of Plasmodium falciparum. However, to the best of our knowledge, no scientific study has been published describing the antimalarial potential of these extracts through in vivo efficacy testing. This study aimed to determine the safety and antimalarial efficacy of the T. ivorensis stem bark aqueous extract (TiH2O) in a mouse model using the OECD 423 protocol and the suppressive and curative murine malaria models, and to predict in silico the pharmacokinetic properties and drug-likeness of two major phytochemical constituents. The in vivo antimalarial efficacy was assessed using the P. berghei NK65-infected mice. The TiH2O treatment impact on biochemical parameters was measured using established standard procedures. The pharmacokinetics prediction was achieved through the pkCSM predictor and Swiss ADME. The TiH2O extract was nontoxic in BALB/c mice at a lethal dose of 50 (LD50) &gt; 2000 mg/kg. The TiH2O extract displayed strong antimalarial efficacy with 100% parasitemia suppression at 200 mg/kg b.w. after 4 days of treatment while its oral administration at 400 mg/kg b.w. in the curative model significantly decreased P. berghei parasitemia by 94.07% with a median efficacy dose (ED50) of 96.80 mg/kg. The administration of TiH2O extract restored the histological parameters disrupted by P. berghei, and the transaminase (ALT and AST) activity, creatinine, and bilirubin levels significantly decreased compared to the negative control mice. In silico explorations showed that the main constituents leucodelphidin (leucodelphinidin) and ellagic acid of the TiH2O extract have drug-like properties, thus indicating that T. ivorensis might constitute a promising source of antimalarial chemical entities with good pharmacokinetics and drug-like properties. The results obtained further corroborated the preliminary in vitro antiplasmodial studies of T. ivorensis stem bark aqueous extract. The metabolome of TiH2O extract should be further profiled in the prospects of characterizing novel natural product scaffolds to support antimalarial drug discovery.

Evaluation of Andrographis paniculata-supplemented Diet on the reproductive indices of Plasmodium berghei-infected mice

Ethnopharmacological relevanceThe King of Bitters (Andrographis paniculata) is a plant used to cure a wide range of infectious diseases which includes malaria, fever and others. However, there is a paucity of scientific evidence of its effect on male reproductive indices during malaria treatment. Aim of the studyThe aim of this study is to evaluate the effect of supplemented diet on antiplasmodial, hematological and male reproductive indices in mice infected with Plasmodium berghei. Materials and methodsAqueous extract of A. paniculata (King of Bitters, KGB) was prepared and the total phenol and flavonoid contents were determined. Forty-two mice, weighing 20–25 g, were distributed into 7 groups consisting of 6 mice each. The mice were innoculated with strain NK65 Plasmodium berghei (Chloroquine, CQ sensitive) and the parasitemia suppression was assessed. The mice were fed with the dietary supplementation of KGB at varying inclusions (2.5%, 5%, 7.5%, and 10%) and administered 10 mg/kg CQ (which served as the positive control) for 5 consecutive days after infection was established. The reactive malondialdeahyde (MDA), antioxidant [superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH)] and the hematological (hemoglobin, packed cell volume and red blood cell) parameters in the infected mice were determined. The reproductive indices (serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sperm count, sperm motility, and sperm viability) and testis histopathology were also assessed. ResultThe result revealed that KGB had a total phenol content of 32.55 mgGAE/g and total flavonoid content of 19.71 mgQUE/g. The infected mice treated with the dietary supplementation of KGB showed significantly decreased (p < 0.05) parasitaemia and MDA levels. Furthermore, the 7.5% dietary inclusion showed significant improvement in the antioxidant, hematological and reproductive indices as well as the restoration of testis morphology as seen in the histopathology plate of the infected mice treated with KGB. Hence, this study suggests that the KGB- supplemented diet (7.5%) may be a potential alternative and complementary therapy in the treatment of malaria infection and reproductive disorders.

Evaluation of the antimalarial and CD4+ T-cell modulatory effects of leaf methanol extract of Phyllanthus muellerianus (Kuntze) Exell (Phyllanthaceae) in Plasmodium berghei-infected mice

Ethnopharmacological relevancePhyllanthus muellerianus (Kunze) Exell, a member of the Phyllanthaceae family, is a medicinal plant widely distributed in Africa. Decoctions from the leaves are used in Nigeria to treat fevers, convulsions, some neurological disorders and malaria. Aim of the studyThis study is to evaluate the anti-malarial properties of methanol extract of Phyllanthus muellerianus (MEPM) leaves and its ethyl acetate fraction using a murine malaria model infected with Plasmodium berghei. Additionally, we seek to investigate the potential modulatory effects of this extract and fraction on CD4+ T-cell populations in the context of malaria infection. Materials and methodsThe anti-malarial effects of the leaf methanol extract of Phyllanthus muellerianus (MEPM) were screened using three established in vivo models of anti-plasmodial screening namely the curative, suppressive and prophylactic models. The methanol extract (MEPM) was afterwards fractionated into hexane (HFPM), ethyl acetate (EAFPM), and methanol (MFPM) fractions. In the pilot anti-malarial screening of the fractions, EAFPM exhibited the best antiparasitic activity. Subsequently, EAFPM was screened for anti-malarial activity using the three models above. The effects of the MEPM and EAFPM on haematological indices (Hb and PCV) of the inoculated animals were further screened and the mean survival time (MST) of the animals was monitored. CD4+ T cells of various groups were counted before and after treatment using a flow cytometer. The EAFPM was further subjected to HPLC analysis for identification of its major compounds. ResultsThe EAFPM (100 and 200 mg/kg) elicited 88% and 93% cure respectively in the curative model, while artesunate (5 mg/kg,- the positive control) gave 87% protection. The MEPM and EAFPM also gave significant suppression of parasitemia in the suppressive model. The treated groups survived beyond 28 days as against 11 days by the control group (infected but not treated). The treated groups also prevented anaemia seen in the negative control. The EAFPM group significantly modulated the CD4+ T cell.Compounds identified were Gallocatechin, Quercetin -3-O-gallate, Ellagic acid, and Methylellagic acid rhamnoside). ConclusionThe study established that the leaf of Phyllanthus muellerianus possesses antimalarial activity, thus lending support to its use in the folkloric treatment of malaria.

A Study on Justicia flava (Forssk.) Vahl.: Pharmacognostic Characterization and Antiplasmodial and Anti-Inflammatory Properties of the Leaves

Justiciaflava (Acanthaceae) is utilized in folk medicine for treating malaria, inflammatory conditions, and respiratory infections. In this study, the antiplasmodial and anti-inflammatory activities of the 70% hydroalcoholic leaf extract of J. flava (JFE) were investigated. The antiplasmodial activity was assessed by the suppressive test and Rane’s curative test. The carrageenan-induced paw oedema assay in chicks was used to assess the anti-inflammatory activity. In Rane’s curative test, JFE significantly suppressed the parasitaemia level ( p &lt; 0.0001) by 56.85%, 63.85%, and 77.85% at 30, 100, and 300 mg·kg−1, respectively. The highest suppression of parasitaemia in the suppressive test was 51.31% at 300 mg·kg−1. The extract prolonged the survival time of infected mice significantly and prevented weight loss and hypothermia which are cardinal signs of P. berghei-induced infection. JFE inhibited foot oedema in chicks with a maximum percentage inhibition of 54.00 ± 5.20%. Pharmacognostic characterization of J. flava revealed it to have simple, petiolate, oppositely arranged leaves which are broadly lanceolate in shape with entire to slightly crenate margins. Microscopy of the leaf showed wavy-walled epidermal cells, diallelocytic stomata, abundant clothing and secretory trichomes, pitted vessels, collateral conjoint vascular bundles, cystoliths, and prismatic calcium oxalate crystals. Flavonoids, tannins, phytosterols, triterpenoids, coumarins, alkaloids, and saponins were detected in the plant. This study has provided important parameters for the correct identification of J. flava and given the scientific credence to its antimalarial and anti-inflammatory effects in traditional medicine. J. flava is a potential source of new antimalarial and anti-inflammatory compounds.

Leukocyte Profile of Mice Infected with Plasmodium berghei and Treated with Aqueous Extract of Strychnos Ligustrina and Its Combination with Dihydroartemisinin Piperaquine Phosphate (DHP)

Malaria is still one of the most highly pathogenic diseases, which remains a significant problem for public health. Natural compounds are alternative ways as an antimalarial compound that are applied for the artemisinin combination. The aim of this study was to determine the effect of a combination of S. ligustrina extract and DHP on the differential leukocytes percentages. This study used 100 mice which were divided into five groups. Group A and B were used for the healthy mice and infected-untreated groups, respectively. Group C used as a controlled drug, received 222 mg/kg BW of DHP. Group D received 300 mg/kg BW of aqueous extract of S. ligustrina. Group E received a combination between 111 mg/kg BW of DHP and 200 mg/kg BW of aqueous extract S. ligustrina. The findings demonstrated that DHP and S. ligustrina extract had an impact on neutrophils, lymphocytes, inhibition, and percentages of parasitemia. The findings revealed that treatment groups C, D, and E reduced the percentage of parasitemia. The percentage of neutrophils in treated groups was significantly higher than in group A (P&lt;0.05). The percentage of lymphocytes was lower in the treated groups, while the percentages of eosinophils, monocytes, and basophils did not significantly different (P&lt;0.05). This study found that group D and E had the same effect on the leucocyte profile as group C. Our findings suggest that the aqueous extract of S. ligustrina, as well as the combination treatment with DHP, have the potential to lead to the discovery of new antimalarial medicines.

In Vivo Efficacy of Curcumin and Curcumin Nanoparticle in Trypanosoma congolense, Broden 1904 (Kinetoplastea: Trypanosomatidae)-Infected Mice.

Curcumin (CUR) is known for its wide folkloric effects on various infections; however, its solubility status has remained a hindrance to its bioavailability in the host. This study evaluated the comparative effects of CUR and CUR-nanoparticle in vitro on T. congolense, T. b. brucei, and T. evansi. Additionally, CUR and CUR-nanoparticle anti-Trypanosoma efficacy were assessed in vivo against T. congolense. All the CUR-nanoparticles were two folds more effective on the T. congolense as compared to CUR in vitro, with recorded efficacy of 3.67 ± 0.31; 7.61 ± 1.22; and 6.40 ± 3.07 μM, while the CUR-nanoparticles efficacy was 1.56 ± 0.50; 28.16 ± 9.43 and 13.12 ± 0.13 μM on T. congolense, T. b. brucei, and T. evansi, respectively. Both CUR and CUR-nanoparticles displayed moderate efficacy orally. The efficacy of CUR and CUR-nanoparticles in vivo was influenced by solubility, presence of food, and treatment period. CUR-treated mice were not cured of the infection; however, the survival rate of the orally treated mice was significantly prolonged as compared with intraperitoneal-treated mice. CUR-nanoparticles resulted in significant suppression of parasitemia even though relapsed was observed. In conclusion, CUR and CUR-nanoparticles possess moderate efficacy orally on the trypanosomes as compared to the intraperitoneal treatment.

Identification of Novel, Potent, and Selective Compounds against Malaria Using Glideosomal-Associated Protein 50 as a Drug Target.

Phylum apicomplexan consists of parasites, such as Plasmodium and Toxoplasma. These obligate intracellular parasites enter host cells via an energy-dependent process using specialized machinery, called the glideosome. In the present study, we used Plasmodium falciparum GAP50, a glideosome-associated protein, as a target to screen 951 different compounds from diverse chemical libraries. Using different screening methods, eight compounds (Hayatinine, Curine, MMV689758 (Bedaquiline), MMV1634402 (Brilacidin), and MMV688271, MMV782353, MMV642550, and USINB4-124-8) were identified, which showed promising binding affinity (KD < 75 μM), along with submicromolar range antiparasitic efficacy and selectivity index > 100 fold for malaria parasite. These eight compounds were effective against Chloroquine-resistant PfINDO and Artemisinin-resistant PfCam3.1R359T strains. Studies on the effect of these compounds at asexual blood stages showed that these eight compounds act differently at different developmental stages, indicating the binding of these compounds to other Plasmodium proteins, in addition to PfGAP50. We further studied the effects of compounds (Bedaquiline and USINB4-124-8) in an in vivoPlasmodium berghei mouse model of malaria. Importantly, the oral delivery of Bedaquiline (50 mg/kg b. wt.) showed substantial suppression of parasitemia, and three out of seven mice were cured of the infection. Thus, our study provides new scaffolds for the development of antimalarials that can act at multiple Plasmodium lifecycle stages.

Evaluation of 4-Aminoquinoline Hydrazone Analogues as Potential Leads for Drug-Resistant Malaria.

The emergence of resistance to first-line antimalarial drugs calls for the development of new therapies for drug-resistant malaria. The efficacy of quinoline-based antimalarial drugs has prompted the development of novel quinolines. A panel of 4-aminoquinoline hydrazone analogues were tested on the multidrug-resistant K1 strain of Plasmodium falciparum: IC50 values after a 48 h cycle ranged from 0.60 to 49 µM, while the 72 h cycle ranged from 0.026 to 0.219 μM. Time-course assays were carried out to define the activity of the lead compounds, which inhibited over 50% growth in 24 h and 90% growth in 72 h. Cytotoxicity assays with HepG2 cells showed IC50 values of 0.87-11.1 μM, whereas in MDBK cells, IC50 values ranged from 1.66 to 11.7 μM. High selectivity indices were observed for the lead compounds screened at 72 h on P. falciparum. Analyses of stage specificity revealed that the ring stages of the parasite life cycle were most affected. Based on antimalarial efficacy and in vitro safety profiles, lead compound 4-(2-benzylidenehydrazinyl)-6-methoxy-2-methylquinoline 2 was progressed to drug combination studies for the detection of synergism, with a combinatory index of 0.599 at IC90 for the combination with artemether, indicating a synergistic antimalarial activity. Compound 2 was screened on different strains of P. falciparum (3D7, Dd2), which maintained similar activity to K1, suggesting no cross-resistance between multidrug resistance and sensitive parasite strains. In vivo analysis with 2 showed the suppression of parasitaemia with P. yoelii NL (non-lethal)-treated mice (20 mg/kg and 5 mg/kg).

Antimalarial activity test and GC-MS analysis of ethanol and ethyl acetate extract of snake plant (Sansevieria trifasciata Prain)

Snake plant or Mother-in-law's tongue (Sansevieria trifasciata Prain) is a plant possessing of many ethnobotanical uses one of which is for medicinal. Previous pharmacological studies showed that this plant has several properties such as healing lesions, anthelmenthic, antimicrobial and cytotoxic. This research was conducted to investigate phytocompounds constituents of ethanol and ethyl acetate of S. trifasciata and their antimalarial activity potential. The phytochemical constituents were analyzed using Gas Cromatography and Mass Spectroscopy (GCMS). The antiplasmodial properties of the extract against malaria parasites were determined by calculating the percentage of parasitaemia suppression which was then used as a variable in probit analysis to determine the IC50 value of the extract. There were 4 and 24 constituents of compounds detected using GC-MS in the ethanol and ethyl acetate extracts of the plant leaves respectively. Antiplasmodial assay of the extracts showed that ethyl acetate solvent gave stronger suppression against Plasmodium falciparum with an IC50 value of 21,29 µg/mL compared to ethanol solvent with an IC50 value of 21,29 µg/mL In conclusion plant leaf extract of Sansevieria trifasciata is potential to be developed as antimalarial ingredient.

Toxicity Studies and in vivo Antiplasmodial Evaluation of Leaf and Stem Bark Extracts of Terminalia avicennioides

Malaria is one of the most serious infectious diseases found in the tropics and subtropics. P. falcifarum resistance to almost all anti-malarial drugs has necessitated the search for anti-malarial compounds. The aim of this study is to investigate the antiplasmodial effects of crude leaf and stem bark extracts of T. avicennioides, a plant utilized by traditional healers in Northern Nigeria to treat malaria and other ailments. Brine shrimp lethality (cytotoxicity) assay and acute toxicity were also evaluated, which are considered a useful tool for preliminary assessment of toxicity in plant extracts. The median lethal dosage (LD50) was calculated by administering different doses of the extract (100–4000 mg/kg) intraperitoneally to three groups of three mice each for 24 hours and observing the animals for physical sign of toxicity. Three models were employed to assess the extracts antiplasmodial effectiveness in vivo against the rodent malaria parasite Plasmodium berghei: suppressive, curative, and repository. The leaf and stem bark extracts were found to show significant toxicity to brine shrimp larvae of Artemia salina in the brine shrimp lethality test with LC50 values of &gt;1000 and 29.6 respectively. Excitation, paw licking, and death were symptoms of acute toxicity of the extracts based on physical and behavioral observations. Death was recorded at 1000 mg/Kg of the stem bark extract and the LD50 is ≤100 mg/Kg body weight while for the leaf extract it was estimated to be ≤600 mg/Kg with no death record. In vivo evaluation revealed that the extracts significantly (P &lt;0.05) reduced parasite count in all models (suppressive, curative and prophylactic), with high average percentage inhibition of parasitaemia (54.68, 58.67 and 65.61%) seen in both T. avicennioides leaf and stem bark extracts, which was comparable to that produced by chloroquine and artesunate, respectively (64.31&amp;93.1; 70.08&amp;80.67; 63.40&amp;75.20%). Both extracts had moderate antiplasmodial activity and were non-toxic to mice and brine shrimps. This finding validates the plant's traditional use in malaria treatment.

Evaluation of the in-vivo Antiplasmodial Activities of Ochna membranacea (Oliv) Ochnaceae Leaves and Stembark extracts in mice

Malaria is an infectious disease with high mortality rate in Africa. Development of resistance to antimalarial drugs in current clinical use such as chloroquine and Artemisinin; along with poor health systems and funding shortfalls have elevated the importance of continuous search for novel antimalarial agents. The lead compounds from which chloroquine and artemisinin were derived were isolated from plants. Therefore, there is high potential for the discovery of new and effective treatment from plants. Ochna membranacea (Oliv) Ochnaceae is among several plants used traditionally against infectious diseases including malaria with no scientific validation. This study investigated the antiplasmodial effect of the crude methanol leaves extract and crude methanol stembark extract of Ochna membranacea coded OMCLE and OMCSE respectively against Plasmodium berghei chloroquine-resistant strain. Acute toxicity studies were carried out using standard protocol. The prophylactic, suppressive and curative effects of the extracts were evaluated at the doses of 500, 1000 and 1500 mg/kg using Ryley and Peters’ method. Chloroquine (5 mg/kg) and artesunate (5 mg/kg) were used as standard drugs in the suppressive and curative tests, while 1.2 mg/kg pyrimethamine was used as standard in the prophylactic test. The oral median lethal dose (LD50) was estimated to be &gt; 5000 mg/kg. All graded doses of OMCLE gave a statistically significant (P&lt;0.05) prophylactic effect. Only the median and highest doses of OMCSE gave significant inhibition of parasitaemia. In the suppressive test, all tested doses of both extracts exhibited significant suppression of parasitaemia compared to the negative control. In conclusion, the study suggests that O. membranaceapossesses antiplasmodial activity making it a potent candidate in the search for newer antimalarials.

Antioxidant and Antimalarial Activities of Methanol Extract of Picralima nitida Root Bark

Ethnomedically, the root, stem bark, seed or leaves of Picralima nitida are relevant in local preparations as antimalaria, antipyretic, antihypertensive and gastrointestinal agents. This study was therefore designed to determine the antimalarial and antioxidant effects of the methanol extract of the root bark of Picralima nitida using standard procedures. The antioxidant activity of the methanol root bark extract was evaluated using 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging method and ferric reducing antioxidant power (FRAP) assay. The antimalarial activity of the methanol root bark extract was investigated using the 4-day suppressive test in mice infected with Plasmodium berghei. The extract showed a concentration-dependent antioxidant activity with 50% inhibitory concentration (IC50) for free radical scavenging activity of 10.19 µg/mL, while the FRAP value was 0.17 ± 0.00 mM FSE/g Extract. The extract demonstrated significant antimalarial activity with 68.33% and 67.27% parasitaemia suppression at doses of 400 mg/kg and 800 mg/kg, respectively. The present study has shown that the root bark extract of P. nitida has antioxidant and antimalarial activities. This study does not only validate the claimed ethnomedicinal use of the plant as antimalaria but also has shown the plant as a potential source of active antimalarial agent.

Antimalarial potential, LC–MS secondary metabolite profiling and computational studies of Zingiber officinale

Malaria is among the top-ranked parasitic diseases that pose a threat to the existence of the human race. This study evaluated the antimalarial effect of the rhizome of Zingiber officinale in infected mice, performed secondary metabolite profiling and detailed computational antimalarial evaluation through molecular docking, molecular dynamics (MD) simulation and density functional theory methods. The antimalarial potential of Z. officinale was performed using the in vivo chemosuppressive model; secondary metabolite profiling was carried out using liquid chromatography–mass spectrometry (LC–MS). Molecular docking was performed with Autodock Vina while the MD simulation was performed with Schrodinger desmond suite for 100 ns and DFT calculations with B3LYP (6-31G) basis set. The extract showed 64% parasitaemia suppression, with a dose-dependent increase in activity up to 200 mg/kg. The chemical profiling of the extract tentatively identified eight phytochemicals. The molecular docking studies with plasmepsin II and Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) identified gingerenone A as the hit molecule, and MMGBSA values corroborate the binding energies obtained. The electronic parameters of gingerenone A revealed its significant antimalarial potential. The antimalarial activity elicited by the extract of Z. officinale and the bioactive chemical constituent supports its usage in ethnomedicine. Communicated by Ramaswamy H. Sarma