[Investigation of the Efficacy of Cinnamaldehyde, Cannabidiol and Eravacycline in a Malaria Model]. / Sitma Modelinde Cinnamaldehyde, Cannabidiol ve Eravacycline'in Etkinliginin Arastirilmasi.

In this study, it was aimed to investigate the antimalarial activity of cinnamaldehyde (CIN) and cannabidiol (CBD) which have shown various biological activities such as potent antimicrobial activity and eravacycline (ERA), a new generation tetracycline derivative, in an in vivo malaria model. The cytotoxic activities of the active substances were determined by the MTT method against L929 mouse fibroblasts and their antimalarial activity were determined by the four-day test in an in vivo mouse model. In this study, five groups were formed: the CIN group, the CBD group, the ERA group, the chloroquine group (CQ) and the untreated group (TAG). 2.5 x 107 parasites/mL of P.berghei-infected erythrocyte suspension was administered IP to all mice. The determined doses of active substances were given to the mice by oral gavage in accordance with the four-day test and the parasitemia status in the mice was controlled for 21 days with smear preparations made from the blood taken from the tail end of the mice. The IC50 values, which express the cytotoxic activity values of the active substances were determined as 27.55 µg/mL, 16.40 µM and 48.82 µg/mL for CIN, CBD and ERA, respectively. The mean parasitemia rate in untreated mice was 33% on day nine and all mice died on day 11. On the ninth day, when compared with the TAG group, no parasites were observed in the CIN group, while the average parasitemia was 0.08% in the CBD group and 17.8% in the ERA group. Compared to the mice in the TAG group, the life expectancy of the other groups was prolonged by eight days in the CIN group, 12 days in the CBD group and eight days in the ERA group. It has been determined that all three active subtances tested in this study suppressed the development of Plasmodium parasites in an in vivo mouse model and prolonged the life span of the mice. It is thought that the strong antimalarial activity of CIN and CBD shown in the study and the possible positive effect of ERA on the clinical course can be improved by combining them with the existing and potential antimalarial molecules.

Ursolic acid-rich extract presents trypanocidal action in vitro but worsens mice under experimental acute Chagas disease.

Chagas disease is a neglected tropical disease with only two drugs available for treatment and the plant Cecropia pachystachya has several compounds with antimicrobial and anti-inflammatory activities. This study aimed to evaluate a supercritical extract from C. pachystachya leaves in vitro and in vivo against Trypanosoma cruzi. A supercritical CO2 extraction was used to obtain the extract (CPE). Cytotoxicity and immunostimulation ability were evaluated in macrophages, and the in vitro trypanocidal activity was evaluated against epimastigotes and trypomastigotes forms. In vivo tests were done by infecting BALB/c mice with blood trypomastigotes forms and treating animals orally with CPE for 10 days. The parasitemia, survival rate, weight, cytokines and nitric oxide dosage were evaluated. CPE demonstrated an effect on the epi and trypomastigotes forms of the parasite (IC50 17.90 ± 1.2 µg/mL; LC50 26.73 ± 1.2 µg/mL) and no changes in macrophages viability, resulting in a selectivity index similar to the reference drug. CPE-treated animals had a worsening compared to non-treated, demonstrated by higher parasitemia and lower survival rate. This result was attributed to the anti-inflammatory effect of CPE, demonstrated by the higher IL-10 and IL-4 values observed in the treated mice compared to the control ones. CPE demonstrated a trypanocidal effect in vitro and a worsening in the in vivo infection due to its anti-inflammatory activity.

Vitamin C-rich juice co-administration with artemether-lumefantrine ameliorates oxido-inflammatory responses in Plasmodium berghei-infected mice.

This study investigated the effects of co-administration of a commercial juice rich in vitamin C (Vit C) on the antimalarial efficacy of artemether-lumefantrine (AL) in Plasmodium berghei-infected mice. Fifty Balb/c mice were infected with Plasmodium berghei NK65 strain from a donor mouse. Parasitemia was established after 72 h. Animals were grouped into 6 (n = 10) and treated daily for 3 days with normal saline, chloroquine, artemether-lumefantrine (AL), AL plus 50% commercial juice (CJ), and AL plus 50% Vit C supplementation in drinks ad libitum, respectively. Body weight, parasitemia levels, and mean survival time were determined. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), nitrite, malondialdehyde, reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) were determined in the serum and liver tissues. Spleen histopathological changes were determined by H&E staining. Parasitemia was cleared by administration of AL and was not affected by Vit C and CJ supplementation. Vit C significantly prevented body weight reduction in AL-treated mice. CJ and Vit C supplementation to AL-treated mice significantly improved survival proportion compared with AL alone animals. Vit C and CJ supplementation significantly improved reduction of TNF-α, IL-6, and malondialdehyde, and increased GSH, CAT, and SOD in AL-treated mice. Spleen cell degeneration and presence of malaria pigment were reduced in AL-treated animals. The results suggest that ad libitum co-administration of commercial juice and vitamin C with artemether-lumefantrine does not impair its antimalarial efficacy but rather improved antioxidant and anti-inflammatory effects in mice.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

BACKGROUND: Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with ongoing transmission (WHO 2020). The World Health Organization (WHO) estimated that, in 2019, approximately 229 million cases of malaria occurred worldwide, with 94% occurring in the WHO's African region (WHO 2020). Of these malaria cases, an estimated 409,000 deaths occurred globally, with 67% occurring in children under five years of age (WHO 2020). Malaria also negatively impacts the health of women during pregnancy, childbirth, and the postnatal period (WHO 2020). Sulfadoxine/pyrimethamine (SP), an antifolate antimalarial, has been widely used across sub-Saharan Africa as the first-line treatment for uncomplicated malaria sTo examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure?Criteria for considering studies for this review Types of studies Inclusion criteria Randomized controlled trials (RCTs) Quasi-RCTs with randomization at the individual or cluster level conducted in malaria-endemic areas (areas with ongoing, local malaria transmission, including areas approaching elimination, as listed in the World Malaria Report 2020) (WHO 2020) Exclusion criteria Ecological studies Observational studies In vivo/in vitro studies Economic studies Systematic literature reviews and meta-analyses (relevant systematic literature reviews and meta-analyses will be excluded but flagged for grey literature screening) Types of participants Inclusion criteria Individuals of any age or gender, living in a malaria endemic area, who are taking antifolate antimalarial medications (inclu

Medicinal plants used in traditional treatment of malaria in Ethiopia: a review of ethnomedicine, anti-malarial and toxicity studies.

BACKGROUND: Malaria is extremely common in Ethiopia, and it is one of the country's most serious public health and economic problems. Traditional medicines have long been utilized in Ethiopia by people of various ethnic groups. As a result, the goal of this study is to record the use of Ethiopian medicinal herbs that have been used to treat malaria. Also, a critical review of the literature on the therapeutic properties of these and other Ethiopian medicinal plants that have been tested against Plasmodium spp. parasites was conducted with the goal of highlighting neglected studies and fostering further research in this area. METHODS: A comprehensive literature search was performed in Scopus, Web of Science Core Collection, PubMed, Science Direct, Google Scholar, and Scientific Electronic Library Online (SciELO) from August 2021 to October 2021. The study databases included original articles published in peer reviewed journals covering anti-malarial plants, dated until October 2021. RESULTS: The review looked at 51 plant species (28 families) that have been used to treat malaria in Ethiopia. The most often used ethnobotanical plant species for the treatment of malaria were Allium sativum, Croton macrostachyus, Carica papaya, and Lepidium sativum. Leaves were used more frequently as a therapeutic preparation than other parts. Plant extracts were found to have very good, good, and moderate anti-malarial activity in mice with rodent Plasmodium species. The most active species were Ajuga remota and Capsicum frufescens, which suppressed parasitaemia by 77.34% and 72.65%, respectively, at an oral dose of 100 mg/kg and an LD50 of above 2000 mg/kg. The compound Aloinoside reported from Aloe macrocarpa leave latex was the most potent; it suppressed parasitaemia by 100% at 400 mg/kg oral dose of Plasmodium berghei infected mice, and its LD50 was above 2000 mg/kg. Toxicity was shown to be safe in 84% of the plant extracts. CONCLUSION: In Ethiopia, medicinal plants have a significant part in reducing the severity of malaria due to their widespread use. As a result, more studies are needed to identify and develop effective novel drugs that could be employed in broader malaria eradication efforts.

Hydroethanolic Extracts of Senna alata Leaves Possess Antimalarial Effects and Reverses Haematological and Biochemical Pertubation in Plasmodium berghei-infected Mice.

The current work investigated the chemical profile, antimalarial potential and capacity of hydroethanolic Senna alata extract (SAE) to reverse hematological and biochemical pertubation in Plasmodium berghei infected mice. Results of the phytochemical analysis revealed the presence of alkaloids, flavonoids, phenolics, tannins, terpenoids, saponins, steroids and cardiac glycosides. Total phenolic and flavonoid content was estimated to be 45.29 ± 2.34 mg GAE/g and 25.22 ± 2.26 mg QE/g respectively. In vitro analysis of the extract also confirmed its antioxidant property. Results of the test for prophylaxis of P. berghei indicated that SAE suppressed parasitemia significantly in treated groups in a dose dependent manner when compared with negative control group. Similarly, SAE improved the mean survival time (MST) and packed cell volume (PCV) of infected mice. The test for curative effect showed that SAE significantly suppressed parasitemia to 4.50 ± 1.05% compared to untreated group 29.83 ± 3.49%. Results of liver and kidney functions indices of treated animals indicated that whereas infection with P. berghei caused increase in the levels of AST, ALT, ALP, urea and creatinine, treatment with SAE significantly reversed the perturbation. Similarly, infected mice were dyslipidemic with concomitant increased activity of HMG CoA reductase and decreased activity of antioxidant enzymes with increase in lipid peroxides levels. However, these alterations were significantly reversed by administration of SAE. Results of this study shows that Senna alata possess antimalarial activity and therefore justify the traditional use of plant for the treatment of malaria.

Antimalarial activity of solvent fractions of a leaf of Eucalyptus globulus labill against Plasmodium berghei infected mice.

INTRODUCTION: The leaf of Eucalyptus globulus is commonly used in the traditional management of malaria. However, the efficacy of solvent fractions are didn't study yet scientifically. Thus, this study aimed to investigate the antimalarial efficacy of the solvent fractions of the leaf of Eucalyptus globulus in mice against P.berghei. METHODS: The antimalarial activity of the fractions was tested in a 4-day suppressive test, Rane's test, and prophylactic test models within P.berghei infected mice. The results were analyzed using a one-way analysis of variance (ANOVA) followed by a post hoc Tukey's test in version 20 SPSS. RESULTS: All fractions at all test doses in the three test models suppressed parasitemia (p < 0.001) compared to the negative controls. In addition, the CF and EA at all three test doses and the AF at 400 mg/kg in three antimalarial test models showed 50% and above parasitemia suppression. In compliance with this, all fractions at all test doses in all test models prolonged the mean survival time of the mice greater than 12 days, except the AF at a lower dose. All fractions at 400 mg/kg in the three test models prevented (p < 0.001) loss of body weight and rectal temperature compared to the negative controls. Furthermore, all fractions in all test models and doses prevented packed cell volume reduction (p < 0.05 to p < 0.001) compared to the negative controls.. CONCLUSION: The findings of this study showed that CF and EAF had greater antimalarial activity compared to AF. This could be attributed to the presence of few phytochemicals in the AF in contrast to the CF and EAF. Overall, the results of this study further support the in vitro antimalarial activity study and the traditional use of the leaf in the management of malaria.

Probiotic administration enhanced antitrypanosomal effects of diminazene aceturate in dogs experimentally infected with Trypanosoma brucei brucei.

OBJECTIVES: This study demonstrated the enhancing actions of probiotic on the antitrypanosomal effects of diminazene aceturate in dogs experimentally infected with Trypanosoma brucei brucei. METHODS: Twenty (20) apparently healthy adult local dogs of both sexes were randomly divided into five groups each containing four dogs. Group I were uninfected and untreated while groups III, IV and V were infected. Groups II, III, IV and V were administered multispecies probiotic (MSP) and/or diminazene aceturate (DA). Parasitaemia was determined, clinical signs recorded and blood collected for haematology. RESULTS: Results revealed T. b. brucei prepatent periods of 4.75 ± 0.25, (4-5) days and significant decrease of parasitaemia, clinical signs and mortality in groups IV and V compared to group III. Mortalities of 100% (group III), 25% (group IV) and 0% (group V) were recorded. Mean packed cells volume, haemoglobin concentration and red blood cells count showed no significant difference in groups I, II, and V, but were significantly decreased in groups III and IV post-treatment. CONCLUSIONS: The administration of MSP to infected dogs enhanced the antitrypanosomal effects of diminazene aceturate.

Antitrypanosomal activity of hydromethanol extract of leaves of Cymbopogon citratus and seeds of Lepidium sativum: in-vivo mice model.

BACKGROUND: Trypanosomiasis is one of the neglected tropical diseases of both humans and animals which decreases their productivity and causes death in the worst scenario. Unavailability of vaccines, the low therapeutic index of trypanocidal drugs, and the development of resistance lead to the need for research focused on developing alternative treatment options especially from medicinal plants. The present study was aimed to investigate antitrypanosomal activities of leaves of Cymbopogon citratus and seeds of Lepidium sativum in in-vivo mice model. METHODS: The plant extracts were prepared by maceration using 80% methanol and reconstituted with 10% dimethyl sulfoxide (DMSO) to have the desired concentration. The test doses were adjusted to 100, 200 and 400 mg/kg based on the toxicity profile. The plants extracts were administered to the respective groups of mice after the 12th day of field isolate T. congolense inoculation for seven consecutive days. The level of parasitemia, bodyweight, packed cell volume (PCV), and differential white blood cell counts were measured. RESULTS: The in -vivo test results revealed that both plant extracts had dose-dependent antitrypanosomal activity. Both crude extracts showed a significant reduction in parasite load (P < 0.05), increased or prevent the fall of PCV value (P < 0.05), decreased lymphocytosis and increased neutrophil counts (p < 0.05) and improved bodyweight but significant bodyweight increment (P < 0.05) was observed only in C. citratus treated mice compared to the negative and positive controls. CONCLUSION: The present study concluded that the crude extracts of leaves of C. citratus and seeds of L. sativum had antitrypanosomal effects. Both plants extracts reduced parasitemia level, prevented anemia and improved bodyweight of treated mice. Comparative results from all tested parameters showed that the best activities were observed with C. citratus treated groups of mice.

Annona muricata Linn and Khaya grandifoliola C.DC. Reduce Oxidative Stress In Vitro and Ameliorate Plasmodium berghei-Induced Parasitemia and Cytokines in BALB/c Mice.

BACKGROUND: Annona muricata and Khaya grandifoliola are ethnomedicinally used for the treatment of malaria and have been experimentally shown to have an anti-plasmodial effect, but the mechanisms involved are not fully understood. This study investigated the effect of the ethanol extracts of their leaves on parasitemia, radical scavenging and cytokines in Plasmodium berghei ANKA-infected BALB/c mice. METHODS: BALB/c mice were infected with P. berghei and treated with chloroquine, A. muricata or K. grandifoliola extract for 4 days. The percentage of parasitemia and the level of cytokine expression were determined after treatment. Trace element, phytochemical and nitric oxide (NO) scavenging activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging properties assays were done to study the antioxidant effects of AN and KG in vitro. RESULTS: P. berghei consistently increased parasitemia in BALB/c mice. The tested doses (100-, 200-, and 400 mg/kg) of A. muricata and K. grandifoliola attenuated the P. berghei-induced elevation of parasitemia and cytokines (TNF-α, IL-5, and IL-6) in vivo during the experimental period, though not as much as chloroquine. Moreover, both extracts scavenged the DPPH and NO radicals, though A. muricata had more anti-oxidant effect than K. grandifoliola in-vitro. CONCLUSION: The ethanol extracts of A. muricata and K. grandifoliola reduce parasitemia in P. berghei-treated mice BALB/c by scavenging free radicals and reducing cytokines, though the extracts were not as effective as chloroquine.

Delayed reduction of Anaplasma marginale parasitemia and packed cell volume normalization despite prolonged enrofloxacin treatment of cattle co-infected with Trypanosoma vivax.

Although co-infections of Trypanosoma vivax, Anaplasma spp., and Babesia spp. have been reported, knowledge gaps remain that need to be addressed. The present study evaluated the efficacy of enrofloxacin (7.5 mg/kg) against A. marginale in naturally infected cattle and cattle experimentally co-infected with T. vivax by observation of the variation in A. marginale parasitemia and packed cell volume (PCV) for 39 days. Bovines were distributed into two groups, each with six calves: T01 = animals immunosuppressed with dexamethasone and with latent anaplasmosis; T02 = animals immunosuppressed with dexamethasone, with latent anaplasmosis and experimentally co-infected with T. vivax on day 0 (D0). Animals of both groups were immunosuppressed with dexamethasone and received enrofloxacin (7.5 mg/kg) whenever mean values of parasitemia for A. marginale were ≥ 5% per group. Cattle of group T02 were also treated with isometamidium chloride (0.5 mg/kg) on D25. On D17 and D22 to D28 of the study, there was a higher (P ≤ 0.05) A. marginale parasitemia in animals of T02 than in those of T01. Animals of T01 required one enrofloxacin treatment to decrease A. marginale parasitemia, while those from T02 needed five treatments. From D5 to D37 of study, the mean values of PCV for calves from T02 were lower (P ≤ 0.05) than that for calves from T01. In conclusion, bovines co-infected T. vivax needed four more treatments with enrofloxacin to reduce A. marginale parasitemia and keep PCV values within reference standards.

Developmental stages influence in vivo antimalarial activity of aerial part extracts of Schkuhria pinnata.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria remains a dire health challenge, particularly in sub-Saharan Africa. In Uganda, it is the most ordinary condition in hospital admission and outpatient care. The country's meager health services compel malaria patients to use herbal remedies such as Schkuhria pinnata (Lam.) Kuntze ex Thell (Asteraceae). Although in vivo studies tested the antimalarial activity of S. pinnata extracts, plant developmental stages and their effect at different doses remain unknown. AIM OF THE STUDY: This study aims to determine the effect of the plant developmental stage on the antimalarial activity of S. pinnata in mice and to document the acute oral toxicity profile. METHODS: Seeds of S. pinnata were grown, and aerial parts of each developmental stage were harvested. Extraction was done by maceration in 70% methanol. The antimalarial activity was evaluated using chloroquine-sensitive Plasmodium berghei on swiss albino mice, in a chemosuppressive test, at 150, 350, and 700 mg/kg, p.o. Standard drugs used were artemether-lumefantrine (0.57 + 3.43) mg/kg and chloroquine (10 mg/kg) as positive controls. Distilled water at 1 mL/100g was used as a negative control. The Lorke method was adopted to determine the acute toxicity of extracts. RESULTS: The flowering stage extract had a maximum suppression of parasitemia at 700 mg/kg (68.83 ± 4.49%). Extract at other developmental stages also significantly suppressed the parasitemia (in the ascending order) fruiting (50.71 ± 1.87%), budding (54.92 ± 7.56%), vegetative (55.39 ± 2.01%) compared to the negative control (24.7 ± 2.7%), p < 0.05. Extracts from all developmental stages increased survival time, with the flowering stage having the highest survival time at 20.33 ± 0.88 days. All extracts had an LD50 of 2157 mg/kg, implying that extracts are safe at lower doses. CONCLUSION: Together, our findings revealed that the S. pinnata extracts at the flowering stage had superior antimalarial activity compared to other plant developmental stages. Extracts from all developmental stages have demonstrated a dose-dependent suppression of malarial parasites and increased survival time with an LD50 of 2157 mg/kg. Thus, for better antimalarial activity, local communities could consider harvesting S. pinnata at the flowering stage. Further studies are needed to isolate pure compounds from S. pinnata and determine their antimalarial activity.

Diatretol, an α, α'-dioxo-diketopiperazine, is a potent in vitro and in vivo antimalarial.

A fungal metabolite, diatretol, has shown to be a promising antimalarial agent. Diatretol displayed potent in vitro antiparasitic activity against the Plasmodium falciparum K1 strain, with an IC50 value of 378 ng ml-1, as well as in vivo efficacy in a Plasmodium berghei-infected mice model, with ca. 50% inhibition at 30 mg/kg (p.o.).

Sulfadoxine-pyrimethamine parasitological efficacy against Plasmodium falciparum among pregnant women and molecular markers of resistance in Zambia: an observational cohort study.

BACKGROUND: The World Health Organization recommends the provision of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) at 4-week intervals from gestational week 13 to delivery in areas of moderate to high malaria transmission intensity. However, the effect of IPTp-SP has been compromised in some areas due to parasite resistance, raising the importance of parasitological and chemoprophylactic surveillance, and monitoring SP-resistance markers in the Plasmodium falciparum population. METHODS: Between November 2013 and April 2014 in Nchelenge, Zambia, 1086 pregnant women received IPTp-SP at antenatal-care bookings. Blood samples were collected on day 0, and on day 28 post-treatment to test for malaria parasites and to estimate SP parasitological efficacy in the treatment and prevention of parasitaemia. A random sample of 96, day 0 malaria-positive samples were analysed to estimate the prevalence of SP-resistance markers in the P. falciparum population. RESULTS: The overall parasitological and prophylactic failure among women who had paired day 0 and day 28 blood slides was 18.6% (95% CI 15.5, 21.8; 109 of 590). Among pregnant women who had asymptomatic parasitaemia on day 0, the day 28 PCR-uncorrected parasitological failure was 30.0% (95% CI 23.7, 36.2; 62 of 207) and the day 28 PCR-corrected parasitological failure was 15.6% (95% CI: 10.6, 20.6; 32 of 205). Among women who tested negative at day 0, 12.3% (95% CI: 9.0, 15.6; 47 of 383) developed parasitaemia at day 28. Among the 96 malaria-positive samples assayed from day 0, 70.8% (95% CI: 60.8, 79.2) contained the DHPS double (Gly-437 + Glu-540) mutation and 92.7% (95% CI: 85.3, 96.5) had the DHFR triple (Asn-108 + Ile-51 + Arg-59) mutation. The quintuple mutation (DHFR triple + DHPS double) and the sextuple mutant (DHFR triple + DHPS double + Arg-581) were found among 68.8% (95% CI: 58.6, 77.3) and 9.4% (95% CI: 4.2, 16.0) of samples, respectively. CONCLUSION: The parasitological and chemoprophylactic failure of SP, and the prevalence of resistance markers in Nchelenge is alarmingly high. Alternative therapies are urgently needed to safeguard pregnant women against malarial infection.

Intervention of standardized ethanol leaf extract of Annickia polycarpa, (DC.) Setten and Maas ex I.M. Turner. (Annonaceae), in Plasmodium berghei infested mice produced anti-malaria action and normalized gross hematological indices.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is a global public health burden due to large number of annual infections and casualties caused by its hematological complications. The bark of Annickia polycarpa is an effective anti-malaria agent in African traditional medicine. However, there is no standardization parameters for A. polycarpa. The anti-malaria properties of its leaf are also not known. AIM OF THE STUDY: To standardize the ethanol leaf extract of A. polycarpa (APLE) and investigate its anti-malaria properties and the effect of its treatment on hematological indices in Plasmodium berghei infected mice in the Rane's test. MATERIALS AND METHODS: Malaria was induced by inoculating female ICR mice with 1.0 × 107P. berghei-infected RBCs in 0.2 mL (i.p.) of blood. Treatment was commenced 3 days later with APLE 50, 200, 400 mg/kg p.o., Quinine 30 mg/kg i.m. (Standard drug) or sterile water (Negative control) once daily per group for 4 successive days. Anti-malarial activity and gross malaria indices such as hyperparasitemia, mean change in body weight and mean survival time (MST) were determined for each group. Changes in white blood cells (WBCs), red blood cells (RBCs), platelets (PLT) counts, hemoglobin (HGB) concentration, hematocrit (HCT) and mean corpuscular volume (MCV) were also measured in the healthy mice before infection as baseline and on day 3 and 8 after inoculation using complete blood count. Standardization was achieved by UHPLC-MS chemical fingerprint analysis and quantitative phytochemical tests. RESULTS: APLE, standardized to its total alkaloids, phenolics and saponin contents, produced significant (P < 0.05) dose-dependent clearance of mean hyperparasitemia of 22.78 ± 0.93% with the minimum parasitemia level of 2.01 ± 0.25% achieved at 400 mg/kg p.o. on day 8. Quinine 30 mg/kg i.m. achieved a minimum parasitemia level of 6.15 ± 0.92%. Moreover, APLE (50-400 mg/kg p.o.) evoked very significant anti-malaria activity of 89.22-95.50%. Anti-malaria activity of Quinine 30 mg/kg i.m. was 86.22%. APLE also inverse dose-dependently promotes weight gain with the effect being significant (P < 0.05) at 50 mg/kg p.o. Moreover, APLE dose-dependently increased the MST of malaria infested mice with 100% survival at 400 mg/kg p.o. Quinine 30 mg/kg i.m. also produce 100% survival rate but did not promote (P > 0.05) weight gain. Hematological studies revealed the development of leukocytopenia, erythrocytosis, microcytic anemia and thrombocytopenia in the malaria infected mice which were reverted with the treatment of APLE 50-400 mg/kg p.o. or Quinine 30 mg/kg i.m. but persisted in the negative control. The UHPLC-MS fingerprint analysis of APLE led to identification of one oxoaporphine and two aporphine alkaloids (1-3). Alkaloids 1 and 3 are being reported in this plant for the first time. CONCLUSION: These results indicate that APLE possessed significant anti-malaria, immunomodulatory, erythropoietic and hematinic actions against malaria infection. APLE also has the ability to revoke deleterious physiological alteration produced by malaria and hence, promote clinical cure. These properties of APLE are due to its constituents especially, aporphine and oxoaporphine alkaloids.

Antrocaryon micraster (A. Chev. And Guillaumin) stem bark extract demonstrated anti-malaria action and normalized hematological indices in Plasmodium berghei infested mice in the Rane's test.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is caused by infection with some species of Plasmodium parasite which leads to adverse alterations in physical and hematological features of infected persons and ultimately results in death. Antrocaryon micraster is used to treat malaria in Ghanaian traditional medicine. However, there is no scientific validation of its anti-malaria properties. The plant does not also have any chemical fingerprint or standardization parameters. AIM OF THE STUDY: This study sought to evaluate the anti-malaria activity of standardized A. micraster stem bark extract (AMSBE) and its effect on mean survival time (MST) and body weight reduction of Plasmodiumberghei infested mice. And to study the effect of treatment of AMSBE on hematological indices of the P. berghei infested mice in order to partly elucidate its anti-malarial mechanism of action. MATERIALS AND METHODS: Malaria was induced in female ICR mice by infecting them with 0.2 mL of blood (i.p.) containing 1.0 × 107P. berghei-infested RBCs from a donor mouse and leaving them without treatment for 3 days. AMSBE or Lonart (standard control) was then orally administered at 50, 200 and 400 mg/kg or 10 mg/kg once daily for 4 consecutive days. The untreated control received sterile water. Malaria parasitemia reduction, anti-malarial activity, mean change in body weight and MST of the parasitized mice were evaluated. Furthermore, changes in white blood cells (WBCs), red blood cells (RBCs), platelets count, hemoglobin (HGB), hematocrit (HCT) and mean corpuscular volume (MCV) were also determined in the healthy animals before infection as baseline and on days 3, 5 and 8 after infection by employing complete blood count. Standardization of AMSBE was achieved by quantification of its constituents and chemical fingerprint analysis using UHPLC-MS. RESULTS: Administration of AMSBE, standardized to 41.51% saponins and 234.960 ± 0.026 mg/g of GAE phenolics, produced significant (P < 0.05) reduction of parasitemia development, maximum anti-malaria activity of 46.01% (comparable to 32.53% produced by Lonart) and significantly (P < 0.05) increased body weight and MST of P. berghei infected mice compared to the untreated control. Moreover, there were significant (P > 0.05) elevation in WBCs, RBCs, HGB, HCT and platelets in the parasitized-AMSBE (especially at 400 mg/kg p.o.) treated mice compared to their baseline values. Whereas, the non-treated parasitized control recorded significant reduction (P < 0.05) in all the above-mentioned parameters compared to its baseline values. The UHPLC-MS fingerprint of AMSBE revealed four compounds with their retention times, percentage composition in their chromatograms and m/z of the molecular ions and fragments in the spectra. CONCLUSIONS: These results show that A. micraster stem bark possessed significant anti-malaria effect and also has the ability to abolish body weight loss, leucopenia, anemia and thrombocytopenia in P. berghei infected mice leading to prolonged life span. The UHPLC-MS fingerprint developed for AMSBE can be used for rapid authentication and standardization of A. micraster specimens and herbal preparations produced from its hydroethanolic stem bark extract to ensure consistent biological activity. The results justify A. micraster's use as anti-malaria agent.

In vitro and in vivo antiplasmodial activity of hydroethanolic bark extract of Bridelia atroviridis müll. Arg. (Euphorbiaceae) and lc-ms-based phytochemical analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is a life-threatening health problem worldwide and treatment remains a major challenge. Natural products from medicinal plants are credible sources for better anti-malarial drugs. AIM OF THE STUDY: This study aimed at assessing the in vitro and in vivo antiplasmodial activities of the hydroethanolic extract of Bridelia atroviridis bark. MATERIALS AND METHODS: The phytochemical characterization of Bridelia atroviridis extract was carried out by High-Performance Liquid Chromatography-Mass spectrometry (HPLC-MS). The cytotoxicity test on Vero cells was carried out using the resazurin-based assay while the in vitro antiplasmodial activity was determined on Plasmodium falciparum (Dd2 strain, chloroquine resistant) using the SYBR green I-based fluorescence assay. The in vivo assay was performed on Plasmodium berghei-infected rats daily treated for 5 days with distilled water (10 mL/kg) for malaria control, 25 mg/kg of chloroquine sulfate for positive control and 50, 100 and 200 mg/kg of B. atroviridis extract for the three test groups. Parasitaemia was daily monitored using 10% giemsa-staining thin blood smears. At the end of the treatment, animals were sacrificed, blood was collected for hematological and biochemical analysis while organs were removed for biochemical and histopathological analyses. RESULTS: The HPLC-MS analysis data of B. atroviridis revealed the presence of bridelionoside D, isomyricitrin, corilagin, myricetin and 5 others compounds not yet identified. Bridelia atroviridis exhibited good in vitro antiplasmodial activity with the IC50 evaluated at 8.08 µg/mL and low cytotoxicity with the median cytotoxic concentration (CC50) higher than 100 µg/mL. B. atroviridis extract significantly reduced the parasitemia (p < 0.05) with an effective dose-50 (ED-50) of 89 mg/kg. B. atroviridis also prevented anemia, leukocytosis and liver and kidneys impairment by decrease of transaminases, ALP, creatinine, uric acid, and triglycerides concentrations. As well, B. atroviridis extract decreased some pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) levels and significantly improved the anti-inflammatory status (P < 0.01) of infected animals marked by a decrease of IL-10 concentration. These results were further confirmed by the improved of antioxidant status and the quasi-normal microarchitecture of the liver, kidneys and spleen in test groups. Overall, the hydroethanolic bark extract of Bridelia atroviridis demonstrated antimalarial property and justified its use in traditional medicine to manage malaria disease.

In Vitro and In Vivo Antimalarial Activities and Toxicological Assessment of Pogostemon Cablin (Blanco) Benth.

The aim of this study was to investigate the antimalarial activities and toxicity of Pogostemon cablin extracts. In vitro activities against the chloroquine-resistant Plasmodium falciparum K1 strain were assessed by using the Plasmodium lactate dehydrogenase enzyme (pLDH) assay, while in vivo activity against the Plasmodium berghei ANKA strain in mice was investigated using a 4-day suppressive test. The in vitro and in vivo toxicity were determined in Vero cells and mice, respectively. The ethanolic extract possessed antimalarial activity with an IC50 of 24.49 ± 0.01 µg/ml, whereas the aqueous extract showed an IC50 of 549.30 ± 0.07 µg/ml. Cytotoxic analyses of the ethanolic and aqueous extracts revealed a nontoxic effect on Vero cells at a concentration of 80 µg/ml. Based on a preliminary study of in vitro antimalarial activity, the ethanolic extract was chosen as a potential agent for further in vivo antimalarial activity analysis in mice. The ethanolic extract, which showed no toxic effect on mice at a dose of 2000 mg/kg body weight, significantly suppressed parasitemia in mice by 38.41%, 45.12% and 89.00% at doses of 200, 400 and 600 mg/kg body weight, respectively. In conclusion, this study shows that the ethanolic P. cablin extract possesses in vitro and in vivo antimalarial activity without toxic effects.

In Vivo Antimalarial Activity of Crude Fruit Extract of Capsicum frutescens Var. Minima (Solanaceae) against Plasmodium berghei-Infected Mice.

BACKGROUND: The alarming spread of parasite resistance to current antimalarial agents is threatening malaria controlling efforts. This, consequently, urged the scientific community to discover novel antimalarial drugs. Successful and most potent antimalarial drugs were obtained from medicinal plants. Capsicum frutescens is claimed to possess an antiplasmodial activity in Ethiopian and Ugandan folkloric medicine. However, there is a lack of pharmacological evidence for its antiplasmodial activity. This study, hence, was aimed at evaluating the in vivo antiplasmodial activity of C. frutescens in a mouse model. METHODS: The dried fruits of the plant were extracted with 80% methanol using cold maceration. A 4-day suppressive test was employed to ascertain the claimed antiplasmodial effect of the plant. Following inoculation with P. berghei, mice in treatment groups were provided with three dose levels (100, 200, and 400 mg/kg) of the extract, while 2% Tween 80 and chloroquine served as the negative and positive controls, respectively. Weight, temperature, packed cell volume, parasitemia, and survival time were then monitored. RESULTS: The acute oral toxicity study revealed that the crude extract caused no mortality and revealed no overt sign of toxicity. In the 4-day suppressive test, all dose levels of the extract were found to exhibit a significant (p < 0.05) inhibition of parasitemia compared to those of the negative control. Maximum parasite suppression (93.28%) was exerted by the highest dose (400 mg/kg/day) of extract. Also, the extract significantly (p < 0.05) prolonged survival time and prevented body weight loss and reduction in temperature and anemia compared to the vehicle-treated group. CONCLUSION: This investigation found strong evidence that the fruit extract of C. frutescens is endowed with promising antiplasmodial activity. Hence, the plant could serve as a potential source of a newer antimalarial agent.

Plasmodium chabaudi-infected mice spleen response to synthesized silver nanoparticles from Indigofera oblongifolia extract.

Malaria is a worldwide serious-threatening infectious disease caused by Plasmodium and the parasite resistance to antimalarial drugs has confirmed a significant obstacle to novel therapeutic antimalarial drugs. In this article, we assessed the antioxidant and anti-inflammatory activity of nanoparticles prepared from Indigofera oblongifolia extract (AgNPs) against the infection with Plasmodium chabaudi caused in mice spleen. AgNPs could significantly suppress the parasitaemia caused by the parasite to approximately 98% on day 7 postinfection with P. chabaudi and could improve the histopathological induced spleen damage. Also, AgNPs were able to increase the capsule thickness of the infected mice spleen. In addition, the AgNPs functioned as an antioxidant agent that affects the change in glutathione, nitric oxide and catalase levels in the spleen. Moreover spleen IL1ß, IL-6 and TNF-α-mRNA expression was regulated by AgNPs administration to the infected mice. These results indicated the anti-oxidant and the anti-inflammatory protective role of AgNPs against P. chabaudi-induced spleen injury.