Gardenia imperialis K. Schum. is a medicinal plant used in traditional medicine to treat malaria and related symptoms. This bio-guided study aimed at identifying antiparasitic compounds from G. imperialis against the causative agents of malaria (Plasmodium falciparum), visceral leishmaniasis (Leishmania donovani), and sleeping sickness (Trypanosoma brucei brucei). Crude methanolic extracts from the leaf and stem bark of G. imperialis were studied using liquid chromatography–mass spectrometry (LC–MS) and preparative medium/high-performance liquid chromatography (M/HPLC) guided by evidence of antiparasitic activity. The structures of the isolated compounds were elucidated using nuclear magnetic resonance (NMR) and MS. All the extracts, fractions, subfractions, and pure compounds were evaluated for antiparasitic activity. Cytotoxicity was tested against Vero and Raw264.7 mammalian cell lines. The leaf methanolic extract (GIlMeOH) exhibited broad-spectrum antiparasitic activity (IC₅₀ < 11 µg/mL) and low cytotoxicity (median cell cytotoxicity—CC50 >100 µg/mL). The dereplication of the extract and isolation yielded fractions, subfractions, and four flavonoids with improved activity (IC₅₀ values ranging from 0.67 to 23.8 µg/mL). Among the isolated flavonoids, gradenin A (3), salvigenin (4), hispidulin (1), and 5,7,3ʹ-trihydroxy-6,4ʹ,5ʹ-trimethoxyflavone (2) showed potent antitrypanosomal activity with IC₅₀ values of 2.8, 2.5, 16.6, and 9.7 µg/mL, respectively. The antiparasitic activities of gradenin A, salvigenin, and 5,7,3ʹ-trihydroxy-6,4ʹ,5ʹ-trimethoxyflavone are reported here for the first time. The promising antiparasitic profile of the G. imperialis leaf extract and its isolated constituents, particularly and 5,7,3ʹ-trihydroxy-6,4ʹ,5ʹ-trimethoxyflavone (2), gradenin A (3), and salvigenin (4), warrants further investigation into their potential as novel and selective agents against the target parasitic diseases.

Background:Shigellosis is a leading diarrheal disease, posing critical public health challenges in low- and middle-income countries. Rising antibiotic resistance exacerbates treatment limitations. Methods:We screened 560 compounds from the MMV Pathogen and COVID Boxes for in vitro activity against Shigella flexneri, S. sonnei, and S. dysenteriae via resazurin-based microdilution. Cytotoxicity (RAW 264.7 cells) and killing kinetics against S. flexneri were assessed. Results:From the primary screen, 13 compounds (9 from the Pathogen Box, 4 from the COVID Box) showed potent anti-Shigella activity against S. flexneri (MIC ≤10 μM). Among these, seven non-antibiotic Pathogen Box compounds exhibited low-micromolar MICs (0.31-5 μM) and low cytotoxicity (CC50 > 100 μM). The known antibiotic levofloxacin (MMV687798) showed broad-spectrum activity (MIC 0.15-2.5 μM). MMV1804312 (salinomycin) was the most active COVID Box hit (MIC 1.25 μM). Time-kill assays revealed rapid, concentration-dependent bactericidal activity (≥3-log reduction within 4-6 h) for Pathogen Box compounds MMV675997 and MMV021660, while MMV000858 displayed bacteriostatic action. Conclusion:This study identifies several novel, non-antibiotic leads from the MMV Pathogen Box with potent anti-Shigella activity and favorable cytotoxicity profiles, offering promising starting points for further development against drug-resistant shigellosis.

Background Gardenia imperialis is used in Cameroonian traditional medicine to treat malaria and related symptoms. This study aimed to conduct a phytochemical investigation of G. imperialis extracts through bioassay-guided fractionation to identify anti-parasitic compounds. Methods Crude methanolic extracts from the leaves and stem bark were subjected to bioassay-guided fractionation using liquid chromatography–mass spectrometry (LC–MS) and preparative high-performance liquid chromatography (HPLC). The structures of isolated natural products were elucidated by spectroscopic analysis, including NMR and MS. All extracts, fractions, subfractions, and pure compounds were evaluated for cytotoxicity against Vero and Raw264.7 cell lines and for anti-parasitic activity against Plasmodium falciparum (Dd2 and 3D7 strains), Trypanosoma brucei brucei , and Leishmania donovani . Results The leaf methanolic extract (GIlMeOH) exhibited broad-spectrum anti-parasitic activity (IC₅₀ < 11 µg/mL) without cytotoxicity towards mammalian cell lines. Dereplication and isolation yielded fractions, subfractions, and compounds with improved activity (IC₅₀ values ranging from 0.67 to 37.2 µg/mL). Among the isolated compounds, gradenin A, salvigenin, hispidulin, and 5,7,3’-trihydroxy-6,4’,5’-trimethoxyflavone showed potent antitrypanosomal activity with IC₅₀ values of 2.8, 2.5, 16.6, and 9.7 µg/mL, respectively. The anti-parasitic activities of gradenin A, salvigenin, and 5,7,3’-trihydroxy-6,4’,5’-trimethoxyflavone are reported here for the first time. Conclusion The promising anti-parasitic profile of the G. imperialis leaf extract and its isolated constituents, particularly and 5,7,3’-trihydroxy-6,4’,5’-trimethoxyflavone, gradenin A, and salvigenin, supports further investigation into their potential as novel and selective agents against parasitic diseases.

Introduction Schistosomiasis, a neglected tropical disease remains a major public health challenge in sub-Saharan Africa despite widespread use of Praziquantel. In Cameroon, various remedies are traditionally employed for treatment. This study aimed to document such remedies in Loum and Njombe-Penja and evaluate their biological activities against Schistosoma mansoni, with the goal of identifying affordable, community-based antischistosomal agents. Methods An ethnobotanical survey conducted in Loum and Njombe Penja identified 11 herbalists who reported nine medicinal plants from seven families. The Euphorbiaceae family was most represented, and Euphorbia hirta, Euphorbia prostrata, and Alchornea cordifolia were selected for further analysis. Cercaricidal activity was assessed by exposing S. mansoni cercariae to plant extracts (0.4 – 250µg/ml). Antioxidant potential was evaluated using DPPH and FRAP assays, while anti-inflammatory activity was measured via albumin denaturation inhibition. Cytotoxicity was tested on LLC-MK2 cells, and phytochemical composition was analyzed using LC-MS and HPLC-UV-ESI-TOF-MS. Results Methanolic and hexane extracts of E. hirta showed most potent cercaricidal activity with LC₅₀ values of 0.07569 and 0.7994µg/ml, respectively. E. hirta and A. cordifolia showed strong radical scavenging potential (SC₅₀: 0.3012 – 203.7µg/ml). A dose-dependent inhibition of albumin denaturation, with plant extracts outperforming Diclofenac at low concentrations was observed. Cytotoxicity assays indicated low toxicity (IC₅₀: 325.7–550.8µg/ml). The Phytochemical screenings identified metabolites as polyphenols, terpenoids, and steroids. Conclusion These findings suggest that E. hirta, E. prostrata, and A. cordifolia possess cercaricidal, antioxidant, and anti-inflammatory properties. Their rich phytochemical profiles support their potential as effective, low-toxicity antischistosomal remedies suitable for integration into primary health care systems in endemic regions

Schistosomiasis, a parasitic disease transmitted by freshwater snails, affects over 251.4 million people globally, with sub-Saharan Africa bearing 95% of the disease burden. This study evaluates the phytochemical composition, characterizes the bioactive secondary metabolites, antioxidant, anti-inflammatory, and the cercaricidal properties, as well as the biosafety of the methanolic and hexane extracts of Chromolaena odorata. Phytochemical screening of C. odorata extracts identified tannins, flavonoids, and saponins in the methanolic extract and steroids and alkaloids in the hexane extract. LC-MS and HPLC-UVESI-TOF-MS analyses confirmed the presence of polyphenols (flavonoids) and aromatic dicarboxylic acid compounds. Antioxidant analysis revealed strong free radical scavenging potential of the plant extracts. Both extracts demonstrated potent cercaricidal activity against Schistosoma mansoni, with LC50 values as low as 0.2012 and 0.2410 μg/mL, respectively. The anti-inflammatory effects were determined via inhibition of heat-induced albumin denaturation, with plant extracts able to inhibit protein denaturation, particularly the methanolic extract that shows a percentage of inhibition of 73.56% at the highest concentration tested. Cytotoxicity assays on LLCMK2 cells showed low toxicity of the extracts. These findings suggest that crude C. odorata extracts possess antischistosomal, antioxidant, and anti-inflammatory properties, supporting their potential integration into primary healthcare strategies for schistosomiasis control.

The rising prevalence of artemisinin-resistant malaria parasites in Africa underscores the urgent demand for new and effective therapeutic options. Historically, natural products have demonstrated significant anti-Plasmodium efficacy, indicating their potential as a source for malaria drug discovery. Extracts and fractions from Terminalia ivorensis and Terminalia brownii previously exhibited promising anti-Plasmodium potency; however, a thorough assessment of their pharmacodynamics across all asexual blood stages of Plasmodium falciparum and elucidation of their mode of action remains to be conducted. Products from the active fractions of T. ivorensis (TiWEa) and T. brownii (TbMMeOH:Ea) were investigated throughout the asexual-blood and sexual stages of P. falciparum, focusing on their mechanism of inhibition and interaction with some key targets of haemoglobin metabolism. Both active fractions (TiWEa and TbMMeOH:Ea) were fractionated by column chromatography, and the chemical structures of the isolated compound were elucidated through physical and spectroscopic techniques. The resulting compound and subfractions were screened in vitro against P. falciparum strains (Dd2, 3D7, and Dd2-GNF156), stage V gametocytes, and mammalian cells. The pharmacodynamics (stage-specific analysis and killing kinetics) of potent inhibitors were assessed and complemented by the effect on haemozoin formation. The molecular interaction between the potent compound and the two target enzymes was investigated through molecular docking. The fractionation of TiWEa yielded five subfractions (Ti01, Ti02, Ti03, Ti04, Ti05), while TbMMeOH:Ea yielded three subfractions (Tb01, Tb02, Tb03) along with one compound (01) characterized as eschweilenol C. All Subfractions demonstrated good activity on susceptible and multidrug-resistant strains of P. falciparum (3D7 and Dd2) with an IC50 ranging from 0.15 to 5.73 µg/ml. eschweilenol C equally displayed an IC50 of 490.74 and 379.20 nM, respectively, on PfDd2 and Pf3D7. Two top hits subfractions (Ti03; Ti04) from TiWEa and eschweilenol C from TbMMeOH:Ea exhibited a perfect antiplasmodial profile (IC50 < 1 µg/ml); good selectivity (SI > 10) and demonstrated no spontaneous loss of efficacy when tested against mutant resistant strain (PfDd2-GNF156) of P. falciparum. Ti03, Ti04, and eschweilenol C reduced haemozoin production, exhibited killing activity on ring and trophozoite stages and showed significant binding affinity to PfM1AAP and PfM17LAP. This study identifies eschweilenol C as a promising candidate for malaria drug discovery efforts and its significance for further exploration in the context of the emergence of artemisinin-resistant parasites in Africa.

The serendipitous discovery of antiparasitic drugs, such as quinine and artemisinin, of plant origin reveals that searching new chemical pharmacophores from medicinal plants is valuable. The present study sought to explore the antiplasmodial, antileishmanial, and antitrypanosomal activities of Lippia adoensis extracts. Crude extracts of L. adoensis leaves and twigs, which were obtained by extraction using 70% ethanol in water, were assayed for antiplasmodial activity against P. falciparum 3D7 and Dd2 through the SYBR green I-based fluorescence assay; and for antileishmanial, antitrypanosomal, and cytotoxic effects on Leishmania donovani, Trypanosoma brucei brucei, and Vero cells, respectively, using resazurin colorimetric assays. In vitro phytochemical analysis of L. adoensis extracts was performed using standard methods. Moreover, liquid chromatography–mass spectrometry (LC-MS) feature-based detection and molecular networking flow on Global Natural Product Social (GNPS) were also used for the phytochemical screening of L. adoensis extracts. Crude extracts from L. adoensis inhibited the growth of P. falciparum (3D7 and Dd2) (IC50s; (3D7): 10.00 and 97.46 μg/mL; (Dd2): 29.48 and 26.96 μg/mL), L. donovani (IC50s: 22.87–10.52 μg/mL), and T. brucei brucei (IC50s: 2.30–55.06 μg/mL). The extracts were found to be non-cytotoxic to Vero cells, thus yielding median cytotoxic concentrations (CC50s) above 100 μg/mL. In vitro phytochemical analysis of the crude extracts revealed the presence of alkaloids, terpenoids, phenolic compounds, and carbohydrates. The LC-MS tandem molecular networking flow predicted that the extracts contained valsafungin A and bacillamidin in the first cluster, and fatty acids, ketone, and aldehyde derivatives in the second cluster. Overall, the present study demonstrated the antiparasitic effects of L. adoensis extracts, thus justifying the use of this plant in the traditional treatment of fever and malaria conditions. Nevertheless, detailed metabolomic studies and antiparasitic mechanisms of action of the extracts are expected to unveil the potential antiparasitic hit compounds.

Malaria is a significant concern due to the emergence of artemisinin-resistant parasites. This study aims to unveil the selective inhibitory potential of extracts and derivatives of some Niger's plants against Plasmodium falciparum. Plant extracts were screened on chloroquine-sensitive (Pf3D7) and multidrug-resistant (PfDd2) P. falciparum strains using the SYBR Green method, followed by bio-guided fractionation of active extracts. Bio-guided method was used for the isolation. Resazurin-based and hemoglobin quantification assays were used to assess the selectivity on normal RAW cells and erythrocytes, respectively. Among the 27 extracts, five exhibited pronounced activity (IC50 < 5 µg/mL) against multidrug-resistant (PfDd2) and three against sensitive (Pf3D7) strains of P. falciparum. The methanolic extract from Phyllanthus pentandrus displayed the most promising activity the most active on both strains (IC50PfDd2 = 1.85 µg/mL and IC50Pf3D7 = 4.25 µg/mL). Its fractionation led to five fractions, among which the ethyl acetate fraction was the most active (IC50PfDd2 = 3.10 µg/mL). Four compounds were isolated from the ethyl acetate fraction: kaempferol, quercetin, gallic acid, and quercetin-3-O-rutinoside. Active extracts and fractions showed good selectivity on normal RAW cells and erythrocytes. This study validates the medicinal use of Niger ethnomedicine for the treatment of malaria.

African trypanosomiasis remains a critical public health concern, with over 55 million people still at risk of infection. There are several issues associated with the current therapies including toxicity and resistance, which represent the main bottleneck of trypanosomiasis control. Thus, it is urgent to develop novel therapeutic tools with distinct mechanisms of action. The in vitro phenotypic screening of the Merck KGaA Darmstadt German Open Global Health Library (OGHL) against Trypanosoma brucei brucei yielded three potent kinase inhibitors belonging to different chemical series: a phenylcarbonylacrylamide (OGHL00006); a 2,4-di(phenylamino)pyrimidine (OGHL00133); and a 3-(triazol-4-yl)-7-azaindole (OGHL00169). They exhibited low micromolar to nanomolar median inhibitory concentrations (IC50 values of 0.6 µM, 0.007 µM, and 0.25 µM, respectively) and good selectivity when tested on Vero cells (SI > 2). OGHL00006 and OGHL00169 induced a rapid and irreversible growth arrest of T. b. brucei within 4-24 hours of incubation. Interestingly, these two hits have also been reported to display antiplasmodial and/or anthelminthic activities, hinting at a similar mechanism of action across multiple species. Given the significant sequence similarities between the human and trypanosome kinomes, we rationalized the putative mechanisms of action for the identified hits through comparative modeling of protein-ligand complexes. This study suggests promising avenues for drug and/or target repurposing against trypanosomiasis.

Mycobacterium ulcerans , the bacterium causing Buruli ulcer (BU), can potentially develop resistance to existing antibiotics (rifampicin - clarithromycin/ moxifloxacin), underscoring the need for new antimycobacterial treatments. This study screened the Pathogen Box from Medicines for Malaria Venture (MMV) to identify M. ulcerans inhibitors. Four hit compounds were found, including the 2-(6- methylpyridin-2-yl )-N-(pyrimidin-4-yl)thieno[3,2-d]pyrimidin-4-amine MMV688122 as a novel anti- M. ulcerans chemotype. Synthesis of structural analogues of MMV688122 allowed the identification of 2-(4- methylpyridin-2-yl )-N-(pyrimidin-4-yl)thieno[3,2-d]pyrimidin-4-amine MMV1578877 as the most potent, with submicromolar activity. Importantly, this analogue was non-cytotoxic up to 100 µM in human fibroblasts. Structure-activity relationship (SAR) studies indicated the crucial role of the methylpyridin-2-yl group in inhibiting M. ulcerans and the possibility to replace the thienopyrimidine core by a quinazoline. While MMV1578877 showed better metabolic stability than MMV688122, further improvement and testing in real-world M. ulcerans clinical isolates are still required. Further metabolite identification and SAR data should guide the optimization of this novel chemotype to enable in vivo testing. Author Summary Buruli ulcer is a neglected tropical disease that causes severe skin ulcers and long-term disability, mostly affecting people in remote African communities. Current treatments rely on antibiotics that are not always effective and may lead to resistance. In this study, we searched for new drug candidates by testing a library of compounds provided by the Medicines for Malaria Venture (MMV). We discovered a promising new chemical family that can kill the bacteria responsible for Buruli ulcer in the lab. One compound, in particular, showed strong activity without harming human cells. This compound also showed better stability and effectiveness. These findings bring us closer to developing a new, safer, and more effective treatment for Buruli ulcer. ### Competing Interest Statement The authors have declared no competing interest.

ETHNOBOTANICAL RELEVANCE:Malaria remains a significant global health challenge, especially in sub-Saharan Africa, with rising resistance to artemisinin-based therapies highlighting the urgent need for new, effective, and safer treatments from medicinal plants which have been used by the indigenous people. AIM OF THE STUDY:This study investigates the antiplasmodial potential of natural products from Mitragyna inermis. METHODS:Crude extracts from the stem bark and twigs of Mitragyna inermis were prepared using various solvents (water, ethanol/water, ethanol, and methanol) and tested for activity against Plasmodium falciparum strains Dd2 and 3D7 using the SYBR Green I-based fluorescence assay. Cytotoxicity was assessed on Vero cells and erythrocytes employing the resazurin reduction and hemolysis methods, and promising extracts further purified using column chromatography, and the afforded compounds characterized using spectroscopic methods. The pharmacokinetic properties of two promising compounds (ellagic acid and arjungenin) were predicted using Swiss ADME software. RESULTS:The methanolic and ethanol/water extracts showed highly potent antiplasmodial activity (IC50 < 3 μg/mL) and acceptable selectivity (SI > 10). Among the isolated and identified compounds, only compound 1 (ellagic acid) exhibited potent cross-activity (IC50 0.84-1.62 μg/mL (2.77-5.36 μM) against drug-susceptible Plasmodium falciparum 3D7 (Pf3D7) and multidrug-resistant (PfDd2, PfINDO, PfW2, PfK1) Plasmodium falciparum strains. These compounds were isolated from Mitragyna inermis for the first time. Predictably, ellagic acid (1) adheres to the Lipinski's five rules, demonstrating good oral bioavailability, water solubility, high gastrointestinal absorption, non-substrate of permeability glycoprotein (P-gp), non-inhibition of cytochrome P450 (CYP450) and ease of synthesis, indicating safety and promising therapeutic potential. Additionally, among the five unidentified compounds (5-9), compounds 5, 6, 7 and 8 were the overall most potent with IC50 values ranging from 0.21 to 5.38 μg/mL against at least 3 plasmodial strains. CONCLUSION:Beyond ellagic acid which showed a promising antiplasmodial activity and acceptable ADME profile, the potency of compounds 5-8 warrants a detailed investigation as promising starting points for antimalarial drug discovery.

ETHNOPHARMACOLOGICAL RELEVANCE:Drymaria cordata and Macaranga monandra are two medicinal plants traditionally used in Cameroon to treat malaria, but their scientific validation remains unclear. AIM OF THE STUDY:To validate the antiplasmodial action of extracts and fractions derived from Drymaria cordata and Macaranga monandra. MATERIALS AND METHODS:Aqueous, methanolic, ethanolic, and hydroethanolic extracts of D. cordata (whole plant) and M. monandra (bark) were prepared by maceration followed by liquid-liquid partition of actives. Extracts and fractions were screened against chloroquine-sensitive (Pf3D7) and multidrug-resistant (PfDd2) strains of P. falciparum, while selectivity was determined on Vero cells. Stage-specific analysis and killing dynamics of potent fractions were profiled, complemented with UHPLC-MS analysis coupled to in silico prediction of pharmacokinetics of identified metabolites. RESULTS:D. cordata ethanolic extract showed moderate activity (IC50PfDd2: 18.9 μg/mL; IC50Pf3D7: 24.51 μg/mL), while all four M. monandra extracts exhibited good activity (IC50 < 8 μg/mL). The methanolic bark extract (MMBME) was highly potent and selective (IC50PfDd2: 2.46 μg/mL, SI > 203; IC50Pf3D7: 1.02 μg/mL, SI > 487). Fractionation yielded two active fractions from MMBME: F2 (IC50PfDd2: 0.60 μg/mL, IC50Pf3D7: 3.42 μg/mL) and F3 (IC50PfDd2: 0.92 μg/mL, IC50Pf3D7: 2.46 μg/mL). Fractions F2 and F3 arrested ring-stage development, lysed trophozoite-infected red blood cells, and blocked merozoite egress. UHPLC-MS analysis identified 17 metabolites in fractions F2 and F3, including fatty acyls, flavonoids, phenols, terpenes, and coumarins. Lecanoric acid was predicted as a promising antimalarial candidate. CONCLUSIONS:Macaranga monandra bark fractions F2 and F3 are potent sources of antiplasmodial compounds targeting multiple asexual blood stages (ABS).

Malaria, leishmaniasis, and African trypanosomiasis are protozoan diseases that constitute major global health problems, especially in developing countries; however, the development of drug resistance coupled with the toxicity of current treatments has hindered their management. The involvement of certain enzymes (dihydrofolate reductase [DHFR]) or proteins (potassium channels) in the pathogenesis of these protozoan diseases is undeniable. In this study, a series of three DHFR inhibitors (6-5 fused heterocyclic derivatives X, Y, and Z) and one K+ channel blocker (E4031) were screened for their inhibitory effects on Leishmania donovani, Plasmodium falciparum, and Trypanosoma brucei. A resazurin assay was used to assess the antitrypanosomal and antileishmanial activities of the test compounds, whereas the antiplasmodial activity was evaluated through the SYBR Green I test. Moreover, the cytotoxicities of the test compounds were evaluated in Vero, Raw 264.7, and HepG-2 cells using a resazurin-based test, while their pharmacokinetic properties were predicted using the online tool, pkCSM. As a result, compound Y exhibited selective (selectivity index range: from 2.69 to >61.4; Vero, Raw 264.7, and HepG-2 cells) and broad-spectrum antiprotozoal activity against L. donovani promastigotes (IC50: 12.4 µM), amastigotes (IC50: 4.28 µM), P. falciparum (IC50: 0.028 µM), and T. brucei brucei (IC50: 0.81 µM). In addition, compound X inhibited the growth of P. falciparum (IC50: 0.0052 µM) and T. brucei brucei (IC50: 6.49 µM). In silico screening of the active antiprotozoal compounds revealed positive drug likeness scores, as none of the criteria for Lipinski’s rule were violated by these compounds. However, in-depth pharmacokinetic and mechanistic studies are warranted to support the discovery of novel antiprotozoal agents against malaria, leishmaniasis, and African trypanosomiasis by repurposing K+ channel blockers and DHFR inhibitors.

The escalating challenge of malaria management, primarily driven by antimalarial drug resistance, necessitates the urgent exploration of novel therapeutic agents. This investigation focused on characterizing the therapeutic efficacy of an aqueous stem bark extract derived from Enantia chlorantha Oliv (Annonaceae) against the parasitic burden of Plasmodium berghei in a rodent model. Comprehensive assessment revealed noteworthy in vitro antiplasmodial efficacy against both the PfDd2 and Pf3D7 strains of P. falciparum, evidenced by median inhibitory concentrations (IC50) of 1.002 and 19.040 μg/mL, respectively. Moreover, the extract demonstrated a statistically significant, dose-responsive suppression of parasitemia in the in vivo model (p < 0.001), achieving suppression rates between 79.00% and 96.91%. Critically, the administration of the extract mitigated malaria-associated pathophysiology, including the prevention of cachexia, anemia, and elevated leukocyte counts. It concurrently facilitated the functional recovery of hepatic and renal biomarkers (e.g., transaminases, bilirubin, and creatinine), reversed indicators of cellular oxidative stress, and potentially lessened multiorgan structural damage. Collectively, these preclinical findings robustly support the substantial antimalarial capacity of E. chlorantha stem bark extract, providing scientific validation for its ethnobotanical application. Future pharmacological research is now imperative to isolate and chemically identify the specific phytochemical constituents responsible for these observed bioactivities.

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Background: Malaria is a parasitic disease that affects many parts of the globe, especially sub-Saharan Africa. Over time, malaria parasites have become resistant to most antimalarial drugs, including artemisinin. Medicinal plants, which are used in the traditional treatment of malaria can afford effective drugs against this notorious disease. One such plant includes Vernonia blumeoides, which is used in the treatment of parasitic diseases, including malaria. Thus the scientific validation of the use of Vernonia blumeoides in ethnomedicine is of outstanding importance. Objectives: This study sought to investigate the antiplasmodial and antioxidant activity of extracts from Vernonia blumeoides. Methods: Vernonia blumeoides ethanol extract was obtained by maceration, and then subjected to phytochemical screening using standard protocols. The as-prepared extract was partitioned using solvents of increasing polarity to afford hexane, ethyl acetate, n-butanol fractions, and the water residue. The antiplasmodial potential of extract and fractions was determined by the Sybr green method. Antioxidant activity of V. blumeoides extracts was evaluated using DPPH, ABTS and FRAP assays. Cytotoxicity test was performed on murine macrophage Raw cells using the resazurin test. Results: The ethanol extract was obtained as a brown powder and the yield of extraction was found to be 43.95%. The phytochemical screening of this extract revealed the presence of tannins, alkaloids, flavonoids, phenolic compounds, and glycosides. Upon antiplasmodial screening against P. falciparum Dd2 and 3D7, the median inhibitory concentrations (IC50) of extract and fractions from V. blumeoides ranged from 4.70 to >100 µg/ml, with ethyl acetate extract having the lowest IC50 value and highest activity. Vernonia blumeoides extracts exhibited antioxidant activity with median scavenging concentrations ranging from 31.17 to 124.1 µg/mL, 50.84 to 500 µg/mL, and 33.95 to 500 µg/mL for ABTS, DPPH and FRAP assays, respectively. Cytotoxicity test of V. blumeoides extracts on Raw cells revealed non toxicity. Conclusions: This novel contribution demonstrated the antiplasmodial activity of V. blumeoides extracts, thus validating the ethnopharmacological use of this plant in the treatment of malaria symptoms. Nonetheless, in depth studies on the mechanisms of action, in vivo toxicity, as well as pharmacokinetic experiments are warranted for the successful utilization of this plant in ethnomedicine.

The serendipitous discovery of antiparasitic drugs, such as quinine and artemisinin from plant origin reveals that the search for new chemical pharmacophores from medicinal plants is valuable. The present study sought to explore the antiplasmodial, antileishmanial, and antitrypanosomal activities of extracts from Lippia adoensis. Crude extracts of L. adoensis leaves and twigs, which were obtained by extraction using 70% ethanol in water, were assayed for antiplasmodial activity against P. falciparum 3D7 and Dd2 through the SYBR green I-based fluorescence assay; and for antileishmanial, antitrypanosomal, and cytotoxic effects on Leishmania donovani, Trypanosoma brucei brucei, and Vero cells, respectively, using the resazurin colorimetric assays. The phytochemical analysis of the extracts was performed using a liquid chromatography-mass spectrometry (LC-MS) feature-based detection and molecular networking flow on Global Natural Product Social (GNPS). As a result, the crude extracts from L. adoensis inhibited growth of P. falciparum (3D7 and Dd2) (IC50s; (3D7): 10.008 and 97.467 μg/mL; (Dd2): 29.48 and 26.96 μg/mL), L. Donovani (IC50s: 22.879-10.522 μg/mL), and T. brucei brucei (IC50s: 2.3085-55.06 μg/mL). The extracts were found to be non-cytotoxic to Vero cells, thus yielding median cytotoxic concentrations (CC50s) above 100 μg/mL. The LC-MS tandem molecular networking flow predicted that the extracts contain valsafungin A and bacillamidin on the first cluster, and fatty acids, ketone and aldehyde derivatives on the second cluster. Overall, the present study demonstrated the antiparasitic effects of L. adoensis extracts, thus justifying the use of this plant in the traditional treatment of fever and malaria conditions. Nevertheless, detailed metabolomic studies and antiparasitic mechanisms of action of the extracts are expected to unveil the potential antiparasitic hit compounds.

Ethnopharmacological relevance: Shigella infection is a public health problem responsible for approximately 700,000 deaths annually. The management of this disease is impaired by the emergence of multidrug-resistant Shigella species, highlighting the urgent need to search for alternative treatment options. In this regard, investigating medicinal plants traditionally used for the treatment of dysentery, diarrheal infections, and/or associated symptoms in endemic regions might provide an opportunity to identify phytochemicals that could be further used as a basis for the development of future anti-shigella drug candidates. Aim of the study: This study was designed to investigate the anti-shigella and antioxidant-based ethnopharmacological potency of some Cameroonian medicinal plants with an emphasis on pharmacokinetic properties of the identified chemical pharmacophore. Materials and methods: Briefly, plant species were selected and collected based on their ethnopharmacological uses and information reported in the literature. Crude aqueous, ethanolic, methanolic, and hydroethanolic (30:70, v/v) extracts from these plants were prepared and then screened for their anti-Shigella activity against four Shigella strains and cytotoxicity against Vero and Raw cell lines using microdilution and resazurin-based methods, respectively. The antioxidant activities of potent extracts were evaluated using DPPH, ABTS, NO, and FRAP scavenging assays. The chemical profile of potent extracts was performed using the UHPLC-LIT-MS/MS and the pharmacokinetic properties, druglikeness, and likely molecular targets of the chemical scaffolds identified were predicted using SwissADME and SwissTargetPredictor. Results: Thirty-nine (39) plants belonging to 26 plant families were harvested. Out of the 228 extracts tested, 18 extracts originating from 6 plants (15.38 %) were active (MICs 250-1000 mu g/mL) and nontoxic toward Vero (CC50 129.25-684.55 mu g/mL) and Raw cell lines (CC50 336.20 to >1000 mu g/mL). Six potent extracts from the two plants exhibited moderate to potent DPPH (SC50 8.870-54.410 mu g/mL), ABTS (SC50 12.020-27.36 mu g/mL), and NO (SC50 0.02-195.85 mu g/mL) scavenging activities. Later, these extracts showed interesting ferric iron-reducing power (1.28-12.14 mu g equivalent NH2OH/g of extract). The shortest onset of action time (4 and 6 h) observed

The CH2Cl2-MeOH (1:1, v/v) extract of Croton sylvaticus stem bark selectively exhibited good antiplasmodial activity during preliminary screening against the multidrug-resistant (Dd2) and chloroquine sensitive (3D7) strains of Plasmodium falciparum with IC50 values of 10.57 and 18.47 mu g/mL, respectively. After fractionation, the fractions exhibited moderate to good activity with IC50 values ranging from 4.31 to 25.49 mu g/mL. The purification of these fractions led to the isolation of six new labdane-type diterpenoids named sylvacrotonins AF (16), alongside seven known compounds (713). Their structures were determined based on the analysis of their NMR and MS data. The isolated compounds were assessed in vitro for their antiplasmodial activity against Pf3D7 and PfDd2. The new labdane-type diterpenoids showed moderate antiplasmodial activity against the two P. falciparum strains, with compound 6 being the most active, with IC50 values of 11.26 and 21.80 mu g/mL against PfDd2 and Pf3D7, respectively. Cytotoxic assays were performed on African green monkey kidney Vero cells to ensure that the obtained activity was specific to the parasites. Interestingly, all the tested extracts, fractions, and isolated compounds showed acceptable selectivity (SI > 10) against both Plasmodium strains, except fractions CSB-E (SI = 3.93) and CSB-C (SI = 9.22) against Pf3D7. Globally, with resistance indexes (RIs) lower than 1, all the tested samples were found to be more active against multidrug-resistant (PfDd2) than sensitive (Pf3D7) strains. Furthermore, all the isolated compounds exhibited cell cytotoxicity in the normal Vero cell line. The results from this study confirm the use of C. sylvaticus in malaria-endemic countries for its management and suggest that further lead-optimization studies on hit compounds could drive to the identification of potential lead molecules for antimalarial control and eradication.