Anti-malaria Activity Research Articles

DIFFERENCES IN ANTIMALARIAL ACTIVITY OF CITRUS MAXIMA,ANREDERA CORDIFOLIA, COMBINATION SOLANUM LYCOPERSICUM-MALUS DOMESTICA-DAUCUS CAROTA IN MICE INFECTED WITH PLASMODIUM BERGHEI

Malaria drug resistance, both new and old drugs, causes severe symptoms and treatment failure. In order to develop new drug, we screen several plants that potentially used as antimalaria. This study aimed to screen and compare antimalaria activity of Citrus maxima, Anredera cordifolia, Solanum lycopersicum, combination Solanum lycopersicum-Malus domestica-Daucus carota in a mouse model. Balb/ c mice male were divided into six groups (n=5). The dried plants were extracted by maceration using 80% methanol. A 4-day suppressive test was done to ascertain the anti-plasmodial effect of those various plants. After inoculation with Plasmodium berghei, the treatment groups were given 1000 mg/kg of the extract, while 5% RPMI and DHP (Dihydroartemisinine Piperaquine) served as controls. The results of this study revealed that all extracts showed significantly lower parasitemia compared to the negative control. This study showed a percentage parasite suppression of 58.7, 84.3, 77.4, 61.4 and 83.9 % for Anredera cordifolia, Citrus maxima, Solanum lycopersicum, combination Solanum lycopersicum-Malus domestica-Daucus carota and Dihydroartemisinine Piperaquine, respectively. The highest parasite suppression (84.3%) was found in the group given Citrus maxima extract. This study concluded that the fruit extract of Citrus Maxima, Anredera Cordifolia, Solanum Lycopersicum-Malus Domestica-Daucus Carota have different antimalaria activity, Citrus maxima has the best potential as an antimalarial.

Safety assessment of crude aqueous methanol extract of Annona senegalensis stem bark: acute and sub-chronic toxicity studies.

Annona senegalensis Pers., (wild custard apple), is a shrub used traditionally to treat respiratory and skin diseases. Previous studies have demonstrated its anti-malaria, anti-snake envenomation and anti-cancer activities. However, its toxicological profile remains limited, particularly in male and female animals. This study aims to evaluate the safety of crude aqueous methanol extract of Annona senegalensis stem bark (AMEAS) through acute and sub-chronic toxicity studies. The stem bark of A. senegalensis was collected, air-dried, pulverized, and extracted using 70% methanol. Phytochemical screening, elemental analysis, and acute toxicity evaluation were carried out on AMEAS. Sub-chronic toxicity study was conducted on Wistar rats of both sexes at different doses administered orally for 28 days. Elemental analysis revealed the presence of heavy metals and essential mineral elements with the highest contents being calcium (59.88%) and potassium (25.39%). Acute toxicity testing showed no mortality up to 5000 mg/kg, suggesting an LD50 greater than 5000 mg/kg. In the sub-chronic toxicity study, no mortality or significant harmful effects were observed. The blood glucose decreased from 13.68 mMol/L at 250 mg/kg to 10.71 mMol/L at 1000 mg/kg, much lower than the distilled water group (17.06 mMol/L). In conclusion, the extract appeared to be well-tolerated, with no obvious adverse effects. AMEAS is rich in Calcium (Ca) and potassium (K). It has been shown to have LD50 greater than 5000 mg/kg and is assumed to be safe. On repeated use, AMEAS may cause hypoglycemia and weight loss which may be useful in managing diabetes and obesity respectively.

Cytotoxicity, antiplasmodial and antimalarial effects of the spice and medicinal tree Schinus terebinthifolius

Schinus terebinthifolius is a medicinal plant with biological in vitro activity against clinically relevant parasites such as Leishmania amazonensis and L. chagasi. Considering its antiparasitic activity, this work aimed to investigate the in vitro effects of S. terebinthifolius fractions against P. falciparum using SYBR fluorescence tests, its cytotoxicity towards monkey kidney cells and efficacy against malaria in a murine model of P. berghei infection. For the first time, screening results with several extracts and fractions are reported herein. Five out of 16 fractions obtained from leaves, flowers, unripe and ripe berries with dichloromethane, ethyl acetate and butanol solvents used in plant extraction were active against P. falciparum. Two ethyl acetate fractions with no cytotoxicity in vitro presenting selectivity indexes of ≥111 and ≥167 exhibited no antimalarial activity in mice at 500 mg/kg. Preliminary LCMS analysis of the ethyl acetate subfractions showed antiplasmodial effect in vitro with high specific index suggesting that such activity is related to polyphenolics in the fractions, mainly flavonoids. Additional studies should be undertaken to identify the compound(s) with anti-malaria activity.

A candidate antibody drug for prevention of malaria

Over 75% of malaria-attributable deaths occur in children under the age of 5 years. However, the first malaria vaccine recommended by the World Health Organization (WHO) for pediatric use, RTS,S/AS01 (Mosquirix), has modest efficacy. Complementary strategies, including monoclonal antibodies, will be important in efforts to eradicate malaria. Here we characterize the circulating B cell repertoires of 45 RTS,S/AS01 vaccinees and discover monoclonal antibodies for development as potential therapeutics. We generated >28,000 antibody sequences and tested 481 antibodies for binding activity and 125 antibodies for antimalaria activity in vivo. Through these analyses we identified correlations suggesting that sequences in Plasmodium falciparum circumsporozoite protein, the target antigen in RTS,S/AS01, may induce immunodominant antibody responses that limit more protective, but subdominant, responses. Using binding studies, mouse malaria models, biomanufacturing assessments and protein stability assays, we selected AB-000224 and AB-007088 for advancement as a clinical lead and backup. We engineered the variable domains (Fv) of both antibodies to enable low-cost manufacturing at scale for distribution to pediatric populations, in alignment with WHO’s preferred product guidelines. The engineered clone with the optimal manufacturing and drug property profile, MAM01, was advanced into clinical development.

Antimalarial Effects of Ethanolic Leaf Extracts of Azadirachta indica and Ocimum gratissimum, and Their Histologic Effects on Some Organs (Liver, Kidney and Heart) of Plasmodium berghei Infected Albino Mice

Azadirachta indica (Neem) and Ociumum gratissimum (clove Basil) have long been employed locally for the management of malaria. The present study compared antimalaria activities of the ethanolic leaf extracts of the individual plants, and assessed their combined effects on some organs of malaria-infected mice, at the Parasitology and Histopathology units, Federal Medical Centre (FMC), Owerri, from January to March, 2021. The leaves of the different plants were extracted with absolute ethanol (BDL 95%) for the test. Clean albino mice were experimentally infected intraperitoneally with chloroquine-sensitive Plasmodium berghei NK65 strain. Parasitaemia level was determined before parasite inoculation and at 24 hours post treatment period. Histopathological study on the liver, kidney, and heart was carried out using the Paraffin Setions method. Extracts of the leaves were administered orally, while chloroquine administration was intramuscular. The efficacy of the leaf extracts was tested on the P. berghei infected albino mice using the 4-day curative test. The lethal median dose (LD50) recorded for neem and clove basil leaf extracts were 31.62 and 1246.9 mg/kg body weight, respectively. Significant activity against the parasite was produced by infected mice treated with extracts of A. indica and O. gratissimum, and their combinations throughout the treatment period (P<.05). Highest reduction of parasitaemia was observed on day 4. Maximum parasitaemia reduction (78.65%) was attained with 30mg/kg of the combined extracts on the 7th day. Mild pathological lesions were observed in mice treated with A. indica leaf extract. These observations indicate better anti-malaria activity of the combination therapy as compared with the individual extracts of A. indica and O. grassimum, and indicate good antimalarial and protective roles of the plant extracts on the parasitized mice at large, as it slows down development of resistance.

Discovery of the chemical constituents, structural characteristics, and pharmacological functions of Chinese caterpillar fungus

Abstract Caterpillar fungus (Cordyceps sinensis) has been widely used as a traditional Chinese medicine for several decades. It is essential to clarify the product composition, structural characteristics, and pharmacological functions of caterpillar fungus. In this review, we comprehensively and systematically summarized the various bioactive components isolated from caterpillar fungus, including nucleosides, d-mannitol, sterols, flavonoids, fatty acids, amino acids, vitamins, peptides, amides, proximate, and mineral composition. Meanwhile, peptides, nucleosides, and polysaccharides serve as the main active components in this genus, which possess immunomodulatory, antioxidant, anti-allergic, anti-tumor, anti-inflammatory, antibacterial, anti-malaria, and antifungal activities. Consequently, the active components of caterpillar fungus demonstrate a vital source of treatment for various diseases and can be used as possible leads for drug discovery. This article reviews the composition and pharmacological action of caterpillar fungus, which is the key to ensuring the safety and effectiveness of caterpillar fungus, and will be of interest for future research.

Antimalarial activity assay of artesunate-3-chloro-4(4-chlorophenoxy) aniline in vitro and in mice models.

The global spread of multi-drug resistant P. falciparum, P. vivax, and P. malariae strains and absence of long-term effective vaccine makes chemotherapy the mainstay of malaria control strategies in endemic settings. The Mossman's assay and the Organization for Economic Co-operation and Development (OECD), 2001 guideline 423, were used to determine the cytotoxicity and acute oral toxicity of a novel hybrid drug, artesunate-3-Chloro-4(4-chlorophenoxy) aniline (ATSA), in vitro and in vivo, respectively. A modified Desjardins method was used to screen for antiplasmodial activity using P. falciparum (3D7 and W2) strains in vitro. The Peter's 4-day suppressive tests (4DTs) was used to evaluate the in vivo antimalaria activity using P. berghei ANKA strain, lumefantrine resistant (LuR), and piperaquine resistant (PQR) P. berghei lines. In silico prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles was assayed using PreADMET online prediction tool. The reference drug in all experiments was artesunate (ATS). Statistical significance between ATSA's activities in treated and control mice was evaluated by one-way analysis of variance (ANOVA). Results show that inhibitory concentrations-50 (IC50) of ATSA is 11.47 ± 1.3 (3D7) and 1.45 ± 0.26 (W2) against 4.66 ± 0.93 (3D7) and 0.60 ± 0.15 (W2) ng/ml of ATS with a selective index of 2180.91(3D7) and a therapeutic index (TI) of > 71). No mortalities were observed in acute oral toxicity assays and mean weight differences for test and controls were statistically insignificant (P > 0.05). The in vivo activity of ATSA was above 40% with effective dosage-50 (ED50) of 4.211, 2.601, and 3.875mg/kg body weight against P. berghei ANKA, LuR, and PQR lines, respectively. The difference between treated and control mice was statistically significant (P < 0.05). ATSA has high intestinal absorption (HIA) > 95% and has medium human ether-a-go-go related gene (hERG) K+ channel inhibition risks. Preclinical and clinical studies on ATSA are recommended to evaluate its value in developing novel drugs for future management of multi-drug resistant malaria parasites.

Progress of research on prodigiosin

Prodigiosin is a natural red pigment derived primarily from secondary metabolites of microorganisms, especially Serratia marcescens. Prodigiosin has been proven to have antitumor, antibacterial, antimalaria, anti‐insect, antialgae, and immunosuppressive activities, and is gaining increasing important in the global market because of its great potential application value in clinical medicine development, environmental treatment, preparation of food additives, and so on. This paper reviews the progress of the research on prodigiosin.

Evaluating a community engagement model for malaria elimination in Haiti: lessons from the community health council project (2019–2021)

BackgroundCommunity engagement (CE) plays a critical role in malaria control and elimination. CE approaches vary substantially, with more participatory programmes requiring higher levels of adaptive management. This study evaluates the effectiveness of a volunteer-based CE programme developed in Haiti in 2018. The approach was based on local leaders organizing and implementing monthly anti-malaria activities in their communities, and was implemented as part of Malaria Zero Consortium activities.MethodsThis programme evaluation draws on quantitative and qualitative data collected from 23 Community Health Councils (CHCs) over a two-year period (2019–2021) in Grand’Anse department, a malaria hotspot region in Haiti.ResultsMonthly monitoring data showed that 100% of the 23 CHCs remained functional over the two-year period, with an average of 0.90 monthly meetings held with an 85% attendance rate. A high degree of transparency and diversity in membership helped create strong planning and involvement from members. CHCs conducted an average of 1.6 community-based activities per month, directly engaging an average of 123 people per month. High levels of fluctuation in monthly activities were indicative of local ownership and self-organization. This included school and church sensitization, environmental sanitation campaigns, mass education, support for case referrals and community mobilization during mass drug administration (MDA) and indoor residual spraying (IRS) campaigns. Members drew on the tradition of konbit (mutual self-help), local histories of health and development campaigns and a lexicon of “solidarity” in difficult times as they negotiated their agency as community volunteers. Small incentives played both symbolic and supportive roles. Some level of politicization was viewed as inevitable, even beneficial. Rumours about financial and political profiteering of CHC volunteers took time to dispel while the tendency towards vertical planning in malaria control created conditions that excluded CHCs from some activities. This generated resentment from members who felt sidelined by the government malaria programme.ConclusionThe CHC model was effective in promoting group solidarity and community-based anti-malaria activities over a two-year period in Haiti. With the end of the Malaria Zero Consortium in early 2021, there is now an opportunity to better integrate this programme into the primary healthcare system, evaluate the impact of the CHCs on malaria epidemiology, and promote the greater integration of CHCs with active surveillance and response activities.

Antimalarial activity prediction analysis of sticophus hermanni on plasmodium falciparum hexose transporter (PfHT1)

The objective of this study is to investigate S.hermanni's antimalarial action against PfHT1 utilizing an in silico technique. In silico method, developing a protein target database by searching and collecting the protein target structures from the Protein Data Bank (PDB) and the UNIPROT databases. PfHT1 protein (PDB ID 6m20) with glucose control. Download all ligand structures from the PubChem database. Molecular docking analysis with Molegro virtual docker predicts interactions between ligands and protein targets. The last step was docking visualization to display 3D views and their interactions with the discovery studio program. The control compound beta-D-glucopyranose binds PfHT1 at the active site GLN169, GLN305, ASN341, GLY408, ASN311, and GLN305. All active compounds of S.hermanni were able to bind to PfHT1. This indicates that all active compounds enter the cell via hexose transporter 1 (PfHT1) receptors, such as glucose. All active substances of S.hermanni have antimalaria activity through PfHT1inhibition. Almost all active substances used were similar to the control binding sites, but only quinoxaline used different binding sites. The active substance of S.hermanni has a variety of binding affinities to PfHT1.

Production of quinolone derivatives in Escherichia coli

Alkyl-4-quinolones (AQs) are natural compounds synthesized by bacteria. Members of this group are known quorum-sensing molecules. Other biological functions, such as anti-bacterial, anti-algal, antifungal, and anti-malaria activities have also been reported. The synthetic pathways of AQs have been validated in Pseudomonas aeruginosa. Five genes (pqsA–E) are involved in the synthesis of 2-heptyl-4(1H)-quinolone (HHQ). To synthesize HHQ in a microbial system, pqsA–E genes were introduced into Escherichia coli and HHQ and 2-methyl-4(1H)-quinolone (MHQ) were synthesized. After the copy number, construct promoters, and substrate supplements were optimized, 141.3 mg/L MHQ and 242.8 mg/L HHQ were synthesized.

Research progress in chemical constituents, pharmacological activity, and quality markers of Bruceae Fructus

Bruceae Fructus is a Chinese herbal medicine with the chemical constituents mainly including Brucea javanica oil, quassinoids, flavonoids, steroids, triterpenoids, and alkaloids. Modern research demonstrates that Bruceae Fructus has anti-tumor, anti-malaria, anti-inflammatory, and lipid-lowering activities. This paper introduces the resource distribution, chemical constituents, and pharmacological activities of Bruceae Fructus. Further, according to the concept of quality marker(Q-marker), this paper predicts the Q-markers of Bruceae Fructus from the specificity of chemical components, pharmaceutical activity, measurability of chemical constituents, compatibility, and clinical efficacy, aiming to provide a theoretical basis for establishing the quality standard of Bruceae Fructus.

50th anniversary of artemisinin: From the discovery to allele-aware genome assembly of Artemisia annua

Over the past half century, the fight against malaria has been a resounding success mainly due to the discovery of artemisinin. According to the World Health Organization (WHO), morbidity and mortality due to malaria have been cut by half since the promotion of artemisinin-based combination therapy (WHO, 2020). Unlike previously used antimalaria medicines, such as chloroquine and quinolines, artemisinin is a sesquiterpene lactone containing an unusual peroxy group, which is essential for its antimalaria activity.

Investigations of the anti-inflammatory, analgesic, and anti-malarial activities of extract from the leaf of Halea ciliata (Abura leaves)

Background: Halea ciliata (Abura leaves) is a medicinal plant and has long been used for the treatment of several diseases including malaria, pains and inflammation, However, no complete pharmacological study to confirm these effects have been reported. In this study, the anti-inflammatory, analgesic, and antimalarial effects of Halea ciliata were investigated. Methods: The leaf of Halea ciliata was extracted with ethanol. The anti-inflammatory activity was tested using the egg albumin induced paw oedema while the analgesic activities were investigated using the hot-plate and Tail flick tests in mice. The anti-malaria activities were evaluated in Plasmodium berghei infected mice. Results: The crude methanol extract of Halea ciliata had LD50 greater than 5000 mg/kg and contains alkaloid, tannin, flavonoid, glycoside, steroid, terpenoid and saponin. In vivo analysis revealed that the crude extract demonstrated 78.64±4.32 % and 78.09±2.34% inhibition of the Plasmodium berghei parasite, while chloroquine, exhibited 92.12±3.45 % activities. The extract also significantly (p&lt;0.05) suppressed the egg albumin induce paw oedema with percentage inhibition of 13.55±0.34, and 11.88±1.34 at 200 and 400 mg/kg respectively, while the standard drug caused 64.40±2.34 inhibition of paw oedema when compared to the non-treated controls. Similarly, the crude extract demonstrated significant analgesic activities in both the hot plate and tail-flick models. Conclusion: These results suggest that crude methanol extract of Halea ciliata has potent anti-malaria, anti-inflammatory and anti-nociceptive activities.

Antimalaria Activities of Several Active Compounds from Medicinal Plants

Antimalaria Activities of Several Active Compounds from Medicinal Plants

Recent Developments on the Synthesis and Bioactivity of Ilamycins/Rufomycins and Cyclomarins, Marine Cyclopeptides That Demonstrate Anti-Malaria and Anti-Tuberculosis Activity.

Ilamycins/rufomycins and cyclomarins are marine cycloheptapeptides containing unusual amino acids. Produced by Streptomyces sp., these compounds show potent activity against a range of mycobacteria, including multidrug-resistant strains of Mycobacterium tuberculosis. The cyclomarins are also very potent inhibitors of Plasmodium falciparum. Biosynthetically the cyclopeptides are obtained via a heptamodular nonribosomal peptide synthetase (NRPS) that directly incorporates some of the nonproteinogenic amino acids. A wide range of derivatives can be obtained by fermentation, while bioengineering also allows the mutasynthesis of derivatives, especially cyclomarins. Other derivatives are accessible by semisynthesis or total syntheses, reported for both natural product classes. The anti-tuberculosis (anti-TB) activity results from the binding of the peptides to the N-terminal domain (NTD) of the bacterial protease-associated unfoldase ClpC1, causing cell death by the uncontrolled proteolytic activity of this enzyme. Diadenosine triphosphate hydrolase (PfAp3Aase) was found to be the active target of the cyclomarins in Plasmodia. SAR studies with natural and synthetic derivatives on ilamycins/rufomycins and cyclomarins indicate which parts of the molecules can be simplified or otherwise modified without losing activity for either target. This review examines all aspects of the research conducted in the syntheses of these interesting cyclopeptides.

Anti-malaria and hypoglycaemic activities of Diosgenin on alloxan-induced, diabetic Wistar rats

The rising threat of Plasmodium falciparum resistance to Monotherapies has prompted the world health organization (WHO) 2006 guidelines to recommend the use of different anti-malarias. In this study, the anti-malaria and hypoglycaemic activities of Diosgenin, a potent, yet poorly reported saponin was investigated on P. falciparum inoculated and Alloxan-Induced, Diabetic Wistar Rats. Fort two (42) adult male wistar rats of between 100g and 150g were procured, acclimatized (for two weeks), and grouped into seven of six (6) rats per group. While Group 1 (Normal control) received normal rat chow and water ad libitum, groups 2 – 4 received no treatment (untreated), 10 mg/kg body weight of anti-diabetic Metformin and 25 mg/kg body weight of diosgenin respectively after inducing diabetes mellitus (DM) with alloxan monohydrate; whereas, groups 5-7 (all malaria infected) were untreated (negative malaria control), 25 mg/kg body weight of diosgenin and 56 mg/kg body weight of anti-malaria coartem respectively. Following treatment period, blood samples were obtained and assayed for fasting blood sugar, packed cell volume (PCV) and total white blood cell count (TWBCC). From the result, P. falciparum exposed rats showed lowered PCV values than control with observed improvements in coartem (significant at p &lt; 0.05) and diosgenin (insignificant) treatment groups. Also, diabetic, diosgenin treated rats showed an insignificant reduction in blood sugar levels compared to control, even though this change was apparently improved compared to diabetic, untreated group. Again, TWBCC caused notable decrease in diosgenin treated, though this decrease signified a huge recovery compared to untreated rats. Corroborative studies on diosgenin with other systems is recommended.

Anti-malaria and hypoglycaemic activities of Diosgenin on alloxan-induced, diabetic Wistar rats

Anti-malaria and hypoglycaemic activities of Diosgenin on alloxan-induced, diabetic Wistar rats

Antimalarial Activity of Ethanol Extract of Noni Leaves (Morinda citrifolia) towards Parasitemia, Splenomegaly, and Hepatomegaly in Plasmodium berghei ANKA Infected Mice

Introduction: Malaria is one of the infectious diseases found in tropical countries and sub-tropical countries. In 2016 there were an estimated 445,000 people died to malaria. Alternative medicine is needed, such as natural based ingredient. Morinda citrifolia or noni plant is a medicinal plant found in all parts of Indonesia which has many benefits, such as antibacterial, analgesic, anticancer, antioxidant, and anti-inflammatory. The aims of this study were to determine the antimalarial activity of ethanol extract of noni leaves and its effect on splenomegaly and hepatomegaly.Methods: Extract of noni leaves was prepared by maceration using ethanol solvent. In vivo experiments were conducted using Plasmodium berghei infected BALB/c mice treated with the doses of 100, 10, 1 mg/kg body weight(BW) orally of ethanolic extract of noni leaves. Then, the percentage of parasitemia was calculated from day 1 to day 4 after treatment and at the end of the test, mice were sacrificed then spleen and liver were collected. Results: The highest parasite growth was found in the group treated with noni leaves ethanol extract at a dose of 1 mg/kg WB and vice versa. Probit analysis resulted in ED50 was 0.882 mg/kg WB. Spearmen test showed there was no correlation between doses and the size of splenomegaly with p=0,2 and between doses and the size of hepatomegaly with p=0,6.Conclusion: Ethanol extract of noni leaves possessed antimalaria activity and there was no correlation between doses of extract and t he splenomegaly and hepatomegaly.

High-level production of microbial prodigiosin: A review.

Prodigiosin is a natural red pigment derived primarily from secondary metabolites of microorganisms, especially Serratia marcescens. It can also be chemically synthesized. Prodigiosin has been proven to have antitumor, antibacterial, antimalaria, anti-insect, antialgae, and immunosuppressive activities, and is gaining increasing important in the global market because of its great potential application value in clinical medicine development, environmental treatment, preparation of food additives, and so on. Due to the low efficiency of prodigiosin chemical synthesis, high-level prodigiosin of production by microorganisms are necessary for prodigiosin applications. In this paper, the production of prodigiosin by microorganism in recent decades is reviewed. The methods and strategies for increasing the yield of prodigiosin are discussed from the aspects of medium composition, additives, factors affecting production conditions, strain modification, and fermentation methods.