Antimalarial Activity Research Articles

Biological Properties, Health Benefits and Semisynthetic Derivatives of Edible Astraeus Mushrooms (Diplocystidiaceae): A Comprehensive Review.

Edible Astraeus mushrooms are known for their nutritional and culinary benefits and potential therapeutic properties. However, more investigation and discussion are still needed to understand their mechanisms of action regarding observed biological activities and thorough chemical analysis of bioactive compounds. This review provides a comprehensive summary and discussion of the bioactive properties and mode of action of Astraeus extracts and their isolated compounds. It covers their reported antioxidant, anti-inflammatory, antidiabetic, anticancer, anti-tuberculosis, antimalarial, antiviral and antileishmanial activities, as well as their potential benefits on metabolic and cardiovascular health and immune function. The review highlights the significance of the biological potential of isolated compounds, such as sugar alcohols, polysaccharides, steroids, and lanostane triterpenoids. Moreover, the review identifies under-researched areas, such as the chemical analysis of Astraeus species, which holds immense research potential. Ultimately, the review aims to inspire further research on the nutraceuticals or therapeutics of these mushrooms.

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

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

MalariaFlow: A comprehensive deep learning platform for multistage phenotypic antimalarial drug discovery

Malaria remains a significant global health challenge due to the growing drug resistance of Plasmodium parasites and the failure to block transmission within human host. While machine learning (ML) and deep learning (DL) methods have shown promise in accelerating antimalarial drug discovery, the performance of deep learning models based on molecular graph and other co-representation approaches warrants further exploration. Current research has overlooked mutant strains of the malaria parasite with varying degrees of sensitivity or resistance, and has not covered the prediction of inhibitory activities across the three major life cycle stages (liver, asexual blood, and gametocyte) within the human host, which is crucial for both treatment and transmission blocking. In this study, we manually curated a benchmark antimalarial activity dataset comprising 407,404 unique compounds and 410,654 bioactivity data points across ten Plasmodium phenotypes and three stages. The performance was systematically compared among two fingerprint-based ML models (RF::Morgan and XGBoost:Morgan), four graph-based DL models (GCN, GAT, MPNN, and Attentive FP), and three co-representations DL models (FP-GNN, HiGNN, and FG-BERT), which reveal that: 1) The FP-GNN model achieved the best predictive performance, outperforming the other methods in distinguishing active and inactive compounds across balanced, more positive, and more negative datasets, with an overall AUROC of 0.900; 2) Fingerprint-based ML models outperformed graph-based DL models on large datasets (>1000 compounds), but the three co-representations DL models were able to incorporate domain-specific chemical knowledge to bridge this gap, achieving better predictive performance. These findings provide valuable guidance for selecting appropriate ML and DL methods for antimalarial activity prediction tasks. The interpretability analysis of the FP-GNN model revealed its ability to accurately capture the key structural features responsible for the liver- and blood-stage activities of the known antimalarial drug atovaquone. Finally, we developed a web server, MalariaFlow, incorporating these high-quality models for antimalarial activity prediction, virtual screening, and similarity search, successfully predicting novel triple-stage antimalarial hits validated through experimental testing, demonstrating its effectiveness and value in discovering potential multistage antimalarial drug candidates.

Artemisinin and Its Derivatives as Potential Anticancer Agents.

Artemisinin is a natural sesquiterpene lactone obtained from the traditional Chinese medicinal herb Artemisia annua L. (qinghao). Artemisinin and its derivatives share an unusual endoperoxide bridge and are extensively used for malaria treatment worldwide. In addition to antimalarial activities, artemisinin and its derivatives have been reported to exhibit promising anticancer effects in recent decades. In this review, we focused on the research progress of artemisinin and its derivatives with potential anticancer activities. The pharmacological effects, potential mechanisms, and clinical trials in cancer therapy of artemisinin and its derivatives were discussed. This review may facilitate the future exploration of artemisinin and its derivatives as effective anticancer agents.

Efficacy of medicinal plants and their derived biomolecules against Plasmodium falciparum

Many apicomplexan pathogens pose significant threats to humans and domestic animals, with the lack of effective drugs and drug resistance representing major challenges in disease management. To address this, the search for new and potent antimalarial drugs is crucial. Plant-based formulations offer a promising alternative for such drug development. Here, we evaluated the in vitro antiplasmodial activity of nine plant extracts, traditionally used to treat fever-like symptoms in Bangladesh. We assessed the antimalarial activity of plant extracts by using the Plasmodium falciparum 3D7 growth inhibition assay, an invasion assay, and a cytotoxicity assay. Of the nine plants studied, ethanolic and methanolic leaf extracts of Ficus hispida, Streblus asper, and Boerhavia repens exhibited high antiplasmodial activity, with IC50 values of 9.31, 4.13, 9.63 μg/ml (ethanolic) and 15.12, 6.63, 7.58 μg/ml (methanolic), respectively, and minimal toxicity (cell viability >80%). Clerodendrum viscosum displayed antiplasmodial effects with IC50 values of 28.90 μg/ml (ethanolic) and 30.57 μg/ml (methanolic). Adhatoda vasica, Mussaenda corymbosa, and Amaranthus spinosus ethanolic extracts showed antimalarial effects with IC50 values of 61.78 μg/ml, 66.31 μg/ml, and 64.14 μg/ml, respectively. However, methanolic extracts of A. vasica and A. spinosus had IC50 values >100 μg/ml. The ethanolic and methanolic extracts of A. vasica, A. spinosus, F. hispida, S. asper, and B. repens significantly reduced parasitemia by inhibiting invasion into erythrocytes. This study highlights the robust antimalarial activity and low cytotoxicity of leaf extracts of F. hispida, S. asper, and B. repens, indicating the presence of antimalarial compounds that warrant further investigation.

Artemisinin and deoxyartemisinin isolated from Artemisia annua L. promote distinct antinociceptive and anti-inflammatory effects in an animal model

Artemisia annua L., known for antimalarial activity, has demonstrated evidence of anti-inflammatory potential. Previously our research group reported the anti-inflammatory and antinociceptive effect of a sesquiterpene lactone-enriched fraction (Lac-FR) obtained from plant, containing artemisinin and deoxyartemisinin. Both the isolated compounds and Lac-FR evaluated on experimental animal models, in the formalin test showed that deoxyartemisinin reduced both neurogenic pain (56.55 %) and inflammatory pain (45.43 %). These findings were superior to the effect of artemisinin (reduction of 28.66 % and 33.35 %, respectively). In the tail flick test, the antinociceptive effect reported as a percentage of the maximum possible effect (%MPE), deoxyartemisinin showed a lower antinociceptive effect (41.57 %) compared to morphine (75.94 %) in 0.5 h. After 1.5 h, the MPE of deoxyartemisinin (87.99 %) exceeded the effect of morphine (47.55 %), without reversal with naloxone. The MPE of artemisinin (23.3 %) observed after 2 h was lower than deoxiartemisinin, without reversal with the opioid antagonist. Lac-FR and artemisinin demonstrated reductions in ear edema of 43.37 % and 48.19 %, respectively, higher than the effect of deoxyartemisinin (33.64 %). Artemisinin reduced tumor necrosis factor alpha (TNF-α) (76.96 %) more selectively when compared to interleukin-1beta (IL-1β) (48.23 %) and interleukin-6 (IL-6) (44.49 %). Lac-FR showed greater selectivity in IL-6 reduction (56.49 %) in relationship to TNF-α (46.71 %) and IL-1β (45.12 %), whereas deoxyartemisinin selectively reduced TNF-α (37.37 %). The results of our study indicate that the lactones isolated did not have relationship with the opioid system. Deoxyartemisinin showed a higher antinociceptive potential than artemisinin. Whereas, artemisinin showed a higher reduction of inflammation and mediators, with a better anti-inflammatory activity outcome.

Synthesis, characterization, and crystal features of a mixed ligand binuclear Zinc(II) acyl pyrazolone complex: DFT, Hirshfeld surface analysis and anti-malarial activity evaluation

A novel binuclear [Zn2(L2C)2(HQ)2] complex with mixed ligands was synthesized using pyrazolone-based derivative (L2C) (1-(3-chlorophenyl)-5-hydroxy-3-methyl-1H-pyrazol-4-yl)(4-nitrophenyl)methanone) as the primary ligand and 8-hydroxyquinoline (8-HQ) as the secondary ligand. Single crystal analysis revealed that each zinc(II) atom is penta-coordinated, involving four O-atoms from two pyrazolone ligands and two N-atoms from the 8-hydroxyquinoline. Two hydroxyl O-atoms from the 8-hydroxyquinoline also bridge the zinc atoms, leading to a distorted square pyramidal geometry. The structure of the complex was further characterized using 1H NMR, FT-IR, UV–vis, TGA, and elemental analysis. The compounds’ electronic behaviour, stable geometry, MEP surfaces, and FMO analysis were studied using density functional theory (DFT) at the B3LYP level with the LanL2DZ basis set. These theoretical results were compared with the experimental structural data of the [Zn2(L2C)2(HQ)2] complex. The complex was tested for its ability to inhibit Plasmodium falciparum in vitro.

Cimicifugin, a broad-spectrum inhibitor of Theileria annulata and Plasmodium falciparum CDK7.

Cyclin-dependent kinase 7 is an attractive therapeutic target for the treatment of cancers, and a previous report suggested that Plasmodium falciparum CDK7 is a potential drug target for developing new anti-malarial drugs. In this study, we aimed to characterize and evaluate the drug target potential of Theileria annulata CDK7. Theileria annulata is responsible for tropical theileriosis, which induces a phenotype similar to cancerous cells like immortalization, hyperproliferation, and dissemination. Virtual screening of the MyriaScreen II library predicted 14 compounds with high binding energies to the ATP-binding pocket of TaCDK7. Three compounds (cimicifugin, ST092793, and ST026925) of these 14 compounds were non-cytotoxic to the uninfected bovine cells (BoMac cells). Cimicifugin treatment led to the activation of the extrinsic apoptosis pathway and induced autophagy in T. annulata-infected cells. Furthermore, cimicifugin also inhibited the growth of P. falciparum, indicating that it has both anti-theilerial and anti-malarial activities and that TaCDK7 and PfCDK7 are promising drug targets.

An Interpretable Machine Learning Strategy for Antimalarial Drug Discovery with LightGBM and SHAP

Malaria continues to pose a significant global health threat, and the emergence of drug-resistant malaria exacerbates the challenge, underscoring the urgent need for new antimalarial drugs. While several machine learning algorithms have been applied to quantitative structure-activity relationship (QSAR) modeling for antimalarial compounds, there remains a need for more interpretable models that can provide insights into the underlying mechanisms of drug action, facilitating the rational design of new compounds. This study develops a QSAR model using Light Gradient Boosting Machine (LightGBM). The model is integrated with SHapley Additive exPlanations (SHAP) to enhance interpretability. The LightGBM model demonstrated superior performance in predicting antimalarial activity, with an ac-curacy of 86%, precision of 85%, sensitivity of 81%, specificity of 89%, and an F1-score of 83%. SHAP analysis identified key molecular descriptors such as maxdO and GATS2m as significant contributors to antimalarial activity. The integration of LightGBM with SHAP not only enhances the predictive ac-curacy of the QSAR model but also provides valuable insights into the importance of features, aiding in the rational design of new antimalarial drugs. This approach bridges the gap between model accuracy and interpretability, offering a robust framework for efficient and effective drug discovery against drug-resistant malaria strains.

Attenuation of Quorum Sensing Mediated Virulence Factors and Biofilm Formation in Pseudomonas Aeruginosa PAO1 by Substituted Chalcones and Flavonols.

Flavonoids epitomize structural scaffolds in many biologically active synthetic and natural compounds. They showcase a diverse spectrum of biological activities including anticancer, antidiabetic, antituberculosis, antimalarial, and antibiofilm activities. The antibiofilm activity of a series of new chalcones and flavonols against clinically significant Pseudomonas aeruginosa PAO1 strain was studied. Antivirulence activities were screened by analysing the effect of compounds on the production of virulence factors like pyocyanin, LasA protease, cell surface hydrophobicity, and rhamnolipid. The best ligands towards the quorum sensing proteins LasR, RhlR, and PqsR were recognised using a molecular docking study. The gene expression in P. aeruginosa after treatment with test compounds was evaluated on quorum sensing genes including rhlA, lasB, and pqsE. The antibiofilm potential of chalcones and flavonols was confirmed by the efficient reduction in the production of virulence factors and downregulation of gene expression.

Noscapine shows antimalarial activity against Plasmodium falciparum 3D7, its clinical isolate Pf140/SS, and Plasmodium berghei ANKA

Objective: To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain (Pf3D7), its clinical isolate (Pf140/SS), and Plasmodium berghei ANKA (PbA). Methods: Using ring-stage survival assay, phenotypic assessments, and SYBR-green-based fluorescence assay, the antimalarial activities of noscapine were assessed compared with dihydroartemisinin (DHA) in in vivo and in vitro studies. In addition, hemolysis and cytotoxicity tests were carried out to evaluate its safety. RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2 (PfFP-2). Results: The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA, with IC50 values of (7.68±0.88) and (5.57±0.74) nM/mL, respectively, and &gt;95% inhibition of PbA infected rats. Noscapine also showed a safe profile, as evidenced by low hemolysis and cytotoxicity even at high concentrations. Moreover, PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS (P&lt;0.01). Conclusions: Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles, which may be further explored as a therapeutic candidate for the treatment of malaria.

Wide-ranging Study on Synthesis and Biological Evaluation of 1, 2, 3-triazole

Abstract: 1, 2, 3-Traizole is five-membered heterocyclic compounds having three nitrogen at 1, 2 and 3 positions. 1, 2, 3-Triazoles are important five-membered heterocyclic scaffolds due to their widespread biological activities. 1, 2, 3-Triazole derivative can be readily obtained in good to excellent yields through click chemistry, 1, 3-dipolar cycloaddition, Metal Catalysed azide-alyne cycloaddition method. 1, 2, 3-Triazoles showed various biological activities, such as antiinflammatory, anticonvulsant, antineoplastic, antimicrobial, analgesic, antimalarial, antiviral, antiproliferative, and anticancer activities. The objective of this review is to synthesize pharmacological activity of 1,2,3-triazole derivatives documented in recent literature.

Researc h progress on chemical constituents, pharmacological effects, toxicity,and heavy metal enrichment characteristics of Phytolacca plants

In China, the dry roots of Phytolacca acinosa or P. americana in the Phytolacca plants are listed as the traditional Chinese medicine(TCM) Phytolaccae Radix. Phytolacca plants contain triterpenoids, triterpenoid saponins, polysaccharides, antiviral proteins, flavonoids, and other chemical components. The most important compounds are triterpenoids and triterpenoid saponins.Phytolacca plants have anti-inflammatory, anti-tumor, antibacterial, antifungal, antimalarial, deworming, and other activities. In this paper, the chemical constituents, pharmacological effects, toxicity, and heavy metal enrichment characteristics of Phytolacca plants were summarized to provide a theoretical basis for the study of active ingredients and drug development of Phytolacca plants.

Plants from South America: A Systematic Review of Their Antiplasmodial and Antimalarial Activities Based on Ethnopharmacological Use

Plants from South America: A Systematic Review of Their Antiplasmodial and Antimalarial Activities Based on Ethnopharmacological Use

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.

Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria

Malaria remains a global health concern as drug resistance threatens treatment programs. We identified a piperidine carboxamide (SW042) with anti-malarial activity by phenotypic screening. Selection of SW042-resistant Plasmodium falciparum (Pf) parasites revealed point mutations in the Pf_proteasome β5 active-site (Pfβ5). A potent analog (SW584) showed efficacy in a mouse model of human malaria after oral dosing. SW584 had a low propensity to generate resistance (minimum inoculum for resistance [MIR] >109) and was synergistic with dihydroartemisinin. Pf_proteasome purification was facilitated by His8-tag introduction onto β7. Inhibition of Pfβ5 correlated with parasite killing, without inhibiting human proteasome isoforms or showing cytotoxicity. The Pf_proteasome_SW584 cryoelectron microscopy (cryo-EM) structure showed that SW584 bound non-covalently distal from the catalytic threonine, in an unexplored pocket at the β5/β6/β3 subunit interface that has species differences between Pf and human proteasomes. Identification of a reversible, species selective, orally active series with low resistance propensity provides a path for drugging this essential target.

Molecular docking, MD simulation, and MMGBSA-binding free energy estimation study identify antibiotic analogs as potential antimalarials targeting housekeeping proteins of Plasmodium falciparum apicoplast

ABSTRACT Plasmodium falciparum exclusively harbours a non-photosynthetic plastid-like organelle called ‘apicoplast,’ crucial for survival. The apicoplast genome resembles chloroplasts, albeit much reduced at 35 kb. The housekeeping functions of the apicoplast are similar to prokaryotes, and several antibiotics have been reported to kill the malaria parasite by targeting its housekeeping functions. However, a significant structural difference between bacterial and apicoplast housekeeping proteins promotes the discovery of antibiotic analogs specifically targeting apicoplast proteins. In this study, we used a high-throughput virtual screening approach to analyze 80% of structurally similar antibiotic analog libraries against five protein targets, including histone-like protein (PfHU), gyrase A subunit (PfGyrA), RNA polymerase β subunit (PfRpoβ), elongation factor G (PfEF-G), and elongation factor Tu (PfEF-Tu) involved in different housekeeping functions of the apicoplast. This computational screening identified molecules with better binding affinities than those antibiotics shown to have antimalarial activities, suggesting they may be more potent antimalarial compounds. The molecular dynamics simulations study revealed stable conformational changes with strong hydrogen bonds between the protein–ligand complexes. The top-hit antibiotic analogs exhibit favourable drug-like characteristics, making them promising candidates for future clinical studies. We propose further biochemical and phenotypic testing of these antibiotic analogs to develop more effective apicoplast-targeting antimalarials.

Synthesis, characterization, biological evaluation and molecular docking study of some novel phenoxy methyl linked 1,2,3-triazole derivatives bridged with amide functionalities via ‘click chemistry’ approach

Herein, a new series of phenoxy methyl linked 1,4-disubstituted 1,2,3-triazole derivatives (SR1–SR16) was synthesized by click reaction and copper-catalyzed Huisgen [3 + 2] cycloaddition in the presence of copper sulphate and sodium ascorbate. All the newly synthesized compounds were characterized via Mass, 1H NMR, 13C NMR, FT-IR spectroscopy, and elemental analysis and evaluated for their antimalarial and antimicrobial activities. Among the synthesized compounds, SR12 containing naphthyl substituent is found to be the most active compound with IC50 of 18.60 μM in antimalarial activities and SR7 and SR9 were found to exhibit good antimicrobial activity at 600.83 μM and 614.12 μM concentration respectively. The antimalarial activity of the synthesized compounds was further supplemented by molecular docking studies against the PfDHFR (PDB ID- 3QGT) receptor, revealing that the remarkable binding affinity values and key interactions as compared to the standard reference Chloroquine. The drug-likeness properties of these compounds were supported by predicted pharmacokinetics.

Tetrahydropyridine appended 8-aminoquinoline derivatives: Design, synthesis, in silico, and in vitro antimalarial studies

Antimalarial drug resistance is a major obstacle in the ongoing quest against malaria. The disease affects half of the world’s population. The majority of them are toddlers and pregnant women. Needed a potent compound to act on drug-resistant Pf at appropriate concentrations without endangering the host. Envisaged solving this issue through rational drug design by creating a novel hybrid drug possessing two pharmacophores that can act on two marvellous and independent aims within the cell. Synthesized a new series of substituted 4-phenyl-1,2,3,6-tetrahydropyridine (THP) 8-Aminoquinoline-based hybrid analogs which have been integrated with quinoline, chloroquine, pamaquine, and primaquine, which exhibited antimalarial activity against Pf. Out of thirteen 4-phenyl-1,2,3,6-THP appended 8-Aminoquinoline derivatives, the compounds 1j, 1e, 1b, and 1l have exhibited good antimalarial activity against chloroquine-sensitive (3D7) and chloroquine-resistant (RKL-9) strain with the minimum inhibitory concentration. Compound 1b was the most effective and showed consistently good potency against the drug-resistant (RKL-9) strain, although all other arrays showed good antimalarial efficacy. Additional docking and molecular dynamics studies were carried out at several targeting sites to quantify the structural parameters necessary for the activity.

Application of polyethylene glycol 8000 as plasticizer for the development of ellagic acid and Eudragit® EPO based solid dispersions using hot melt extrusion.

Solid dispersion formation by Hot melt extrusion (HME) is a widely used formulation strategy to improve the solubility and bioavailability of poorly water-soluble drugs. Despite this, they are limited by various factors such as drug-excipient miscibility, poor stability, limited drug loading and extrudability of physical drug-excipient mixtures. In this work, polyethylene glycol 8000 (PEG 8000) was used as a plasticizer for the manufacture of ellagic acid solid dispersions (EASD) with high drug loading. Indeed, EA is a polyphenolic active compound with antimalarial and other promising therapeutic activities. However, its low solubility and low permeability limit its therapeutic use. Solid dispersions formation may overcome this challenge, but its high melting point negatively influences the extrudability of its binary physical mixtures with a high drug loading rate, hence the need to use a plasticizer. Thus, five formulations consisting of EA, Eudragit® EPO and PEG 8000 in the ratio of 15:75:10 (F1), 20:70:10 (F2), 25:65:10 (F3), 15:80:5 (F4) and 20:85:5 (F5) % w/w, respectively, have been extruded, four of which were successful. The extrudates were evaluated by X-ray powder diffraction, FTIR spectroscopy and in vitro dissolution tests. Based on the results of these tests, the F5 formulation was identified as the most promising. Indeed, after 15 min of dissolution test, the dissolution rate of ellagic acid from the formulations was 62.67±3.10%, 58.74±7.23 %, 88.75±3.02% and 83.47±4.40% respectively for formulation F1, F2, F4 and F5. Moreover, the results of the FTIR spectroscopy analyses showed stronger interactions between the different constituents in the F4 and 5 formulations compared to the F1 and 2 formulations. Extruded materials of the F5 formulation, characterized by solid state nuclear magnetic resonance (ssNMR) spectroscopy and subjected to stability studies, showed good physical stability for twelve months under real-time stability study conditions and for six months under accelerated conditions.