Identification of Commercial Antimalarial Herbal Drugs Using Laser-Induced Autofluorescence Technique and Multivariate Algorithms.

In malaria-prone developing countries the integrity of Anti-Malarial Herbal Drugs (AMHDs) which are easily preferred for treatment can be compromised. Currently, existing techniques for identifying AMHDs are destructive. We report on the use of non-destructive and sensitive technique, Laser-Induced-Autofluorescence (LIAF) in combination with multivariate algorithms for identification of AMHDs. The LIAF spectra were recorded from commercially prepared decoction AMHDs purchased from accredited pharmacy shop in Ghana. Deconvolution of the LIAF spectra revealed secondary metabolites belonging to derivatives of alkaloids and classes of phenolic compounds of the AMHDs. Principal Component Analysis (PCA) and Hierarchical Clustering Analysis (HCA) were able to discriminate the AMHDs base on their physicochemical properties. Based on two principal components, the PCA- QDA (Quadratic Discriminant Analysis), PCA-LDA (Linear Discriminant Analysis), PCA-SVM (Support Vector Machine) and PCA-KNN (K-Nearest Neighbour) models were developed with an accuracy performance of 99.0, 99.7, 100.0, and 100%, respectively, in identifying AMHDs. PCA-SVM and PCA-KNN provided the best classification and stability performance. The LIAF technique in combination with multivariate techniques may offer a non-destructive and viable tool for AMHDs identification.

Safety and antimalarial therapeutic index of alkaloid-rich extract of Phyllanthus amarus Schumach. & Thonn. in mice.

Background: Malaria fever is known to cause around one million passings per annum. This life-threatening infection is predominant in most part of Africa. Malaria vaccinations are challenging in Nigeria, particularly in rural areas. Drugs derived from plants have been utilized customarily to treat malaria. In this manner, assurance of the harmfulness and antimalarial capacity of plant derived drugs can demonstrate to be the source of novel lead compound to control malaria. The aim of this study was to evaluate the safety and antimalarial therapeutic index of alkaloid-rich extract of Phyllanthus amarus in mice. Methods: Thirty rats (n = 5/group) were used for the oral acute toxicity study and administered with varying doses (0, 100, 500, 1000, 2000 and 5000 mg/kg b.wt) of alkaloid-rich extract of P. amarus. The oral acute toxicity was carried out according to OECD guidelines.After 21 days of monitoring, serum liver function tests and liver histology were performed using documented methods. The antimalarial index was determined using median effective dose (ED50) of thirty five mice divided into 7 groups (n = 5). Results: showed that up to the highest dose (5000 mg/kg), there were no biochemical derangements in liver function. Physical signs of toxicity were also not observed. Antimalarial activity indices showed high potency with therapeutic index of 30.13. Conclusion: Alkaloid-rich extract of Phyllanthus amarus is therefore, non-toxic with reputable antimalarial activity. The active alkaloid(s) deserve further study as source for possible development of new and more potent antimalarial agent.

An updated review on distribution, biosynthesis and pharmacological effects of artemisinin: A wonder drug.

Plant-based drugs have been used for centuries for treating different ailments. Malaria, one of the prevalent threats in many parts of the world, is treated mainly by artemisinin-based drugs derived from plants of genus Artemisia. However, the distribution of artemisinin is restricted to a few species of the genus; besides, its yield depends on ontogeny and the plant's geographical location. Here, we review the studies focusing on biosynthesis and distributional pattern of artemisinin production in species of the genus Artemisia. We also discussed various agronomic and in vitro methods and molecular approaches to increase the yield of artemisinin. We have summarized different mechanisms of artemisinin involved in its anti-malarial, anti-cancer, anti-inflammatory and anti-viral activities (like against Covid-19). Overall the current review provides a synopsis of a global view of the distribution of artemisinin, its biosynthesis, and pharmacological potential in treating various diseases like malaria, cancer, and coronavirus, which may provoke future research efforts in drug development. Nevertheless, long-term trials and molecular approaches, like CRISPR-Cas, are required for in-depth research.

Bioactivity assays and phytochemical analysis upon Alcea glabrata; focusing on xanthine oxidase inhibitory and antimalarial properties.

Alcea glabrata from the family Malvaceae, was selected for evaluating its xanthine oxidase inhibitory, anti-malarial, and antioxidant activities. In addition, some phytochemical analysis upon different extracts of A. glabrata were performed. Aerial parts of the collected A. glabrata plant material were dried and solvent extracted via soxhlet apparatus using different solvents. Various chromatographic techniques were used for extra fractionation of the achieved extracts. Xanthine oxidase (XO) inhibitory, antimalarial and antioxidant activity assays upon different A. glabrata extracts and fractions were carried out and reported in terms of IC50s. Total phenolic and flavonoid contents of the A. glabrata methanol extract (MeOH) were determined using the 2,2-Di Phenyl-1-Picryl Hydrazyl (DPPH) assay, aluminum chloride colorimetric, and Folin-Ciocalteu reagents, respectively. In addition, A. glabrata essential oil was obtained through hydrodistillation by a Clevenger apparatus. Analysis and identification of essential oil compounds were carried out through gas chromatography mass spectrometry (GC-MS) analysis. MeOH extract showed the highest XO inhibitory activity with the IC50 of 0.37 ± 0.12 mg/mL antioxidant activity with the RC50 of 0.24 ± 0.06 mg/mL. While, chloroform extract revealed the strongest antimalarial activity with the IC50 of 0.4 ± 0.05 mg/mL. The total flavonoid and phenolic contents of the A. glabrata methanol extract were 39.8 mg quercetin equivalent and 6.1 g gallic acid equivalent per 100 g of dry plant material, respectively. GC-MS analysis showed that the monoterpenes were prevailing in A. glabrata essential oil where the major constituents: octacosane (30.7%), eugenol (12.3%), and anethole (12.0%). Concerning the results of this study, A. glabrata extracts and its ingredients could be considered as a novel promising herbal medicine in the design and also treatment of new drugs for the relief of gout and malaria diseases.

Exposing the Hepatotoxicity of Medicinal Plants: A Review of Copalchi Stem Bark (Hintonia latiflora) / Exponiendo la hepatotoxicidad de las plantas medicinales: una revisión de palo amargo (Hintonia latiflora)

Resumen Se estima que el 80% de la población mundial utiliza diversas plantas medicinales para el tratamiento o control de diversas enfermedades, ya sean agudas o crónicas, debido a su accesibilidad y bajo costo, observándose en los últimos años un aumento en el consumo sin una observación médica adecuada. México es considerado como el segundo país más importante del mundo en cuanto al conocimiento de la medicina tradicional, solo después de china. El uso de las plantas medicinales se ha reportado desde tiempos prehispánicos como una opción terapéutica, sin embargo, el único enfoque que se tiene es la parte curativa y no se ha reflexionado en que las plantas poseen metabolitos secundarios (compuestos químicos producidos por las plantas con actividad biológica en los seres vivos) que, además de tener efectos terapéuticos poseen efectos tóxicos en las personas que las consumen, observándose en algunos casos efectos reversibles después de suspender su consumo. El copalchi o palo amargo es una planta medicinal que proviene de la corteza del árbol de Hintonia latiflora (sin. Coutarea latiflora), la cual ha sido utilizada principalmente como tratamiento alternativo para pacientes con diabetes tipo 2, ya que se ha demostrado que tiene efecto hipoglucemiante. Sin embargo, se han reportado casos de hepatotoxicidad aguda con un incremento en las transaminasas hepáticas (ALT y AST) por el consumo continuo de dicha corteza, no obstante el procesamiento de las plantas medicinales utilizando medios físicos (calentar o hervir) puede alterar la actividad farmacológica de los constituyentes orgánicos, los cuales pueden verse también afectados en su concentración dependiendo de los factores ambientales de cultivo, localización del suelo, humedad y temperatura ambiental, así como la temporada de cosecha (tallos, hojas, flores, raíces, semillas). El consumo de esta planta medicinal es por medio de infusiones calientes o en cápsulas con extracto.

Abstract Approximately 80% of the world's population uses various medicinal plants for the treatment or control of various diseases, whether acute or chronic, due to their accessibility and low cost, observing in recent years an increase in consumption without proper medical observation. Mexico is considered the second most important country in the world in terms of traditional medicine knowledge, only after China. The use of medicinal plants has been reported since pre-Hispanic times as a therapeutic option; however, the only focus is on the curative part and it has not been considered that plants have secondary metabolites (chemical compounds produced by plants with biological activity in living beings) that, besides having therapeutic effects, have toxic effects in people who consume them, and in some cases reversible effects are observed after suspending their consumption. Copalchi or palo amargo is a medicinal plant obtained from the bark of the Hintonia latiflora tree (syn. Coutarea latiflora), which has been used mainly as an alternative treatment for patients with type 2 diabetes, since it has been shown to have a hypoglycemic effect. However, cases of acute hepatotoxicity have been reported with an increase in hepatic transaminases (ALT and AST) by the continuous consumption of this bark. However, the processing of medicinal plants using physical means (heating or boiling) can alter the pharmacological activity of the organic constituents, which can also be affected in their concentration depending on the environmental factors of cultivation, soil location, humidity, and environmental temperature, as well as the harvesting season (stems, leaves, flowers, roots, seeds). The consumption of this medicinal plant is by means of hot infusions or in capsules with extract.

Anti-malarial plants in Ethiopia and their activities on drug-resistant malaria.

In Ethiopia, the impacts of malaria continue to cause a many number of morbidity and mortality that accounts to most-outpatient observations. Ethiopia recently designed to attain nationwide malaria control by 2030 by beginning sub-national elimination in districts with low malaria transmission. However, the rise of drug-resistant parasites, especially Plasmodium falciparum hinder the malaria-containment strategies. Plasmodium falciparum and Plasmodium vivax are dispersed all over Ethiopia, and account for 60% and 40% of malaria cases, respectively. The aim of this report was to overview the phytochemical constituents, diversity, and effect of some compound extracts on drug-resistant plasmodium species. Many plant species, a total 200 identified by 82 studies, are used in traditional malaria treatments throughout the country. Allium sativum, Croton macrostachyus, and Carica papaya were the more frequently used medicinal plant species. There are so many phytochemical constituents found in medicinal plants used to treat malaria. Alkaloids, flavonoids, phenolics, terpenoids, and glycosides are the most-reported for their effective activity on drug-resistant malaria.

(-)-6-epi-Artemisinin, a Natural Stereoisomer of (+)-Artemisinin in the Opposite Enantiomeric Series, from the Endemic Madagascar Plant Saldinia proboscidea, an Atypical Source.

Chemical and biological investigation of the Madagascar endemic plant Saldinia proboscidea led to the isolation of an isomer of artemisinin, (-)-6-epi-artemisinin (2). Its structure was elucidated using a combination of NMR and mass spectrometry. The absolute configuration was established by chemical syntheses of compound 2 as well as a new stereoisomer (3). The comparable bioactivities of artemisinin (1) and its isomer (-)-6-epi-artemisinin (2) revealed that this change in configuration was not critical to their biological properties. Bioactivity was assessed using an apoptosis induction assay, a SARS-CoV-2 inhibitor assay, and a haematin polymerization inhibitory activity (HPIA) assay. This is the first report of an artemisinin-related compound from a genus not belonging to Artemisia and it is the first isolation of an artemisinin-related natural product that is the opposite enantiomeric series relative to artemisinin from Artemisia annua.

In vitro antiplasmodial activity of Phyllanthus amarus against Plasmodium falciparum and evaluation of its acute toxicity effect in mouse model.

BACKGROUND: The emergence of widespread resistance of Plasmodium species to most antimalarial drugs has led to a more vigorous and concerted research on traditional medicinal plants for the treatment of malaria. OBJECTIVE OF STUDY: The study was aimed to investigate the in vitro antiplasmodial activity of crude ethanolic and aqueous extracts of Phyllanthus amarus against clinical isolates of Plasmodium falciparum in Northwestern Nigeria. MATERIALS AND METHODS: The plant was extracted using two solvents, water and ethanol, where a high yield was obtained from the aqueous extracts (11.9%) as compared to the ethanolic extract (9.64%). The extracts were evaluated in vitro at concentrations of 6.25, 12.5, 25, 50, and 100 µg/ml, and the level of potency in each case was expressed as the concentration of the extract that exhibited a 50% reduction of the parasites relative to control (100%) parasitemia. Artemether-lumefantrine was used as a positive standard in the assay. RESULTS: All extracts showed a significant reduction in parasite growth relative to control (P ≤ 0.05). Ethanolic extract exhibited a higher antiplasmodial activity of 76.8%, half-maximal inhibitory concentration (IC50) of 5.80 µg/ml, and aqueous extract had an activity of 75.3%, IC50 of 7.94 µg/ml. Both extracts exhibited very active antiplasmodial activity. Oral acute toxicity test in the doses of 500, 1000, and 1500 mg/kg showed no sign of toxicity on albino mice after 48 h. CONCLUSION: Although there was an increase in appetite after 24 and 48 h, the findings from this study show that P. amarus possesses a promising antimalarial activity which can be exploited for malaria therapy and justifies the traditional use of the plant in malaria treatment.

Current status of potential therapeutic candidates for the COVID-19 crisis.

As of April 15, 2020, the ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept through 213 countries and infected more than 1,870,000 individuals, posing an unprecedented threat to international health and the economy. There is currently no specific treatment available for patients with COVID-19 infection. The lessons learned from past management of respiratory viral infections have provided insights into treating COVID-19. Numerous potential therapies, including supportive intervention, immunomodulatory agents, antiviral therapy, and convalescent plasma transfusion, have been tentatively applied in clinical settings. A number of these therapies have provided substantially curative benefits in treating patients with COVID-19 infection. Furthermore, intensive research and clinical trials are underway to assess the efficacy of existing drugs and identify potential therapeutic targets to develop new drugs for treating COVID-19. Herein, we summarize the current potential therapeutic approaches for diseases related to COVID-19 infection and introduce their mechanisms of action, safety, and effectiveness.

Potential antimalarial activity of Coccinia barteri leaf extract and solvent fractions against Plasmodium berghei infected mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Coccinia barteri (Hook. F.) is traditional used in Southeast of Nigeria in management of fever. This study aimed to evaluate the antimalarial activities of hydro-methanol crude extract and solvent fractions of Coccinia barteri leaf. MATERIALS AND METHODS: Two animal models employed for the study were, 4-day suppressive and curative assays against chloroquine sensitive Plasmodium berghei NK65. Level of parasitaemia, mean survival time (MST), anal temperature and weight loss were measured to assess antimalarial efficacy of the extract/fractions. Chloroquine (10 mg kg-1) was used as positive control. Chemo-profile of extract was evaluated using GC-MS, HPLC techniques and standard phytochemical analysis. Preliminary toxicity test was done using modified Lorke's method. RESULTS: The crude extract (100-400 mg kg-1) and solvent fractions (20-80 mg kg-1) demonstrated antimalarial activity in both models compared to controls. Semi purified fractions of the extract produced stronger percentage chemosuppression and inhibition of parasite. The % inhibition of the fractions, hexane, chloroform, ethyl acetate and aqueous at 80 mg kg-1 were 96.0 0, 95.29, 89.86 and 96.00% respectively on day 8 (D8). While on D14, 100% parasite clearance, indicating cure was obtained for hexane, chloroform and aqueous fraction treatment groups, no death occurred in these groups. Ethyl acetate fraction treated groups lived longer but were not fully protected. Some marker compounds were identified. CONCLUSIONS: These results support the use of C. barteri as malaria remedy and potential source of antimalarial templates. Long acting parasitaemia reduction effect indicates its possible combination potential in poly-herbal combination therapy.

In vivo studies on the biochemical indices of Plasmodium berghei infected mice treated with Alstonia boonei leaf and root extracts.

BACKGROUND: A study on the biochemical indices of albino mice infected with Plasmodium berghei and treated with Alstonia boonei aqueous and ethanolic extracts was undertaken. METHODS: 216 males mice were randomly assigned to six treatment groups each containing six mice for both aqueous and ethanolic extracts experiments. P. berghei NK-65 was inoculated into the mice intraperitoneally and establishment of infection confirmed. Administration of extracts of was done after phytochemical and acute toxicity tests at varying concentrations, for both suppressive and curative tests. Blood samples collected by ocular puncturing were examined for the biochemical indices; ALT, AST, ALP, creatinine and total protein using the standard procedures. RESULTS: A. boonei extracts suppression of P. berghei in mice was comparable to the standard drug. Significantly higher (p<0.05) recovery of mice treated with A. boonei extracts was observed. The biochemical indices examined all had significantly (p<0.05) increased concentration after 7 days post-infection, except for total protein concentration which had no significant increase or decrease due to A. boonei extracts administration. CONCLUSION: The antiplasmodial potentials of A. boonei leaf and root extracts were dosage and duration-dependent, and have demonstrated satisfactory normalization of altered biochemical indices due to malaria.

Anti-Infective and Anti-Cancer Properties of the Annona Species: Their Ethnomedicinal Uses, Alkaloid Diversity, and Pharmacological Activities.

Annona species have been a valuable source of anti-infective and anticancer agents. However, only limited evaluations of their alkaloids have been carried out. This review collates and evaluates the biological data from extracts and purified isolates for their anti-infective and anti-cancer activities. An isoquinoline backbone is a major structural alkaloid moiety of the Annona genus, and more than 83 alkaloids have been isolated from this genus alone. Crude extracts of Annona genus are reported with moderate activities against Plasmodium falciparum showing larvicidal activities. However, no pure compounds from the Annona genus were tested against the parasite. The methanol extract of Annona muricata showed apparent antimicrobial activities. The isolated alkaloids from this genus including liriodenine, anonaine, asimilobine showed sensitivity against Staphylococcus epidermidis. Other alkaloids such as (+)-Xylopine and isocoreximine indicated significant anti-cancer activity against A549 and K-562 cell lines, respectively. This review revealed that the alkaloids from Annona genus are rich in structural diversity and pharmacological activities. Further exploration of this genus and their alkaloids has potential for developing novel anti-infective and anticancer drugs.

Antimalarial Activity of Hydroalcoholic Root Extract of Acanthus polystachyus Delile (Acanthaceae) Against Plasmodium berghei-Infected Mice.

Failure of the efficacy of antimalarial drugs is recognized in different classes of medicines for treating malaria, which urges the need for new drugs. This study tried to check the in vivo antimalarial activity of the root extracts of Acanthus polystachyus Delile against Plasmodium berghei-infected mice. The study revealed that the methanolic crude extract of the root of Acanthus polystachyus Delile showed significant (P < .01) parasitemia suppressive activities in both models compared with the negative control. Parasitemia suppressive activities were 25.26%, 33.46%, and 51.48% in a 4-day suppressive test and 23.31%, 31.20%, and 43.54% in prophylaxis test at 100, 200, and 400 mg/kg of the extract, respectively, as compared to the negative control. Besides, the extract increases mean survival time significantly in all tested doses in a 4-day suppressive test, but in the prophylaxis model, only mice treated with 200 and 400 mg/kg significantly lived longer. Based on this finding, the root of Acanthus polystachyus Delile has strong antimalarial activity, which may be a good candidate for new antimalarial agents.

What Approaches are Most Effective at Addressing Micronutrient Deficiency in Children 0-5 Years? A Review of Systematic Reviews.

Introduction Even though micronutrient deficiency is still a major public health problem, it is still unclear which interventions are most effective in improving micronutrient status. This review therefore aims to summarize the evidence published in systematic reviews on intervention strategies that aim at improving micronutrient status in children under the age of five. Methods We searched the literature and included systematic reviews that reported on micronutrient status as a primary outcome for children of 0-5 years old, had a focus on low or middle income countries. Subsequently, papers were reviewed and selected by two authors. Results We included 4235 reviews in this systematic review. We found that (single or multiple) micronutrient deficiencies in pre-school children improved after providing (single or multiple) micronutrients. However home fortification did not always lead to significant increase in serum vitamin A, serum ferritin, hemoglobin or zinc. Commercial fortification did improve iron status. Cord clamping reduced the risk of anemia in infants up to 6 months and, in helminth endemic areas, anthelminthic treatment increased serum ferritin levels, hemoglobin and improved height for age z-scores. Anti-malaria treatment improved ferritin levels. Discussion Based on our results the clearest recommendations are: delayed cord clamping is an effective intervention for reducing anemia in early life. In helminth endemic areas iron status can be improved by anthelminthic treatment. Anti-malaria treatment can improve ferritin. In deficient populations, single iron, vitamin A and multimicronutrient supplementation can improve iron, vitamin A and multimicronutrient status respectively. While the impact of home-fortification on multimicronutrient status remains questionable, commercial iron fortification may improve iron status.

Research progress on chemical constituents of Artemisia annua and its pharmacological activities / 中草药

As a commonly used Chinese materia medica, Artemisia annua mainly contains sesquiterpenoids, diterpenes, phenylpropionic acids, coumarins, flavonoids, volatile oil, and other chemical compositions. Its pharmacological activities are anti-malaria, anti-tumor, anti-microbial, anti-parasitic, antipyretic, anti-inflammatory, immunoregulation and so on. The significantly anti-malarial activity has led to its earlier use in the treatment of malaria. In this paper, the chemical constituents and pharmacological activities of A. annua in recent years are reviewed in order to provide a reference for the further development and rational utilization of this plant resource.

Screening of Anti-Malarial Activity of Different Extracts Obtained from Three Species of Scrophularia Growing in Iran.

Scrophularia genus belonging to the family of Scrophulariaceae, is a medicinal plant widely distributed in Iran. In the present study, the anti-malarial activity of different extracts of three Iranian endemic species of Scrophularia including S. frigida, S. subaphylla and S. atropatana, was screened by an in-vitro preliminary assay. The plant materials were extracted successively with n-hexane, dichloromethane (DCM), and methanol (MeOH) at room temperature by soxhlet extractor. In order to assess anti-malarial activity of obtained extracts, cell free ß-hematin formation assay was applied. Amongst the extracts, DCM extract of S. frigida exhibited remarkable anti-malarial activity with IC50 value of 0.67 ± 0.11 mg/mL. In contrast, MeOH and n-hexane extracts of all plants illustrated insignificant or moderate activity in this assay. Furthermore, preliminary phytochemical analysis along with TLC and GC-MS analysis of potent extract (DCM extract of S. frigida) were performed for more clarification. These methods revealed that the notable anti-malarial activity might be due to the presence of active constituents like methoxylated flavonoids, methylated coumarins, and diterpenoids. From the nine extracts of different species of Scrophularia, DCM extract of S. frigida showed potent inhibitory activity on ß-hematin formation assay. Hence, it seems that it is noteworthy to concentrate on purifying the active chemical constituents of DCM extract and determining the pure anti-malarial components.

Phytochemical Analysis and In-vitro Bioactivity of Scrophularia umbrosa Rhizome (Scrophulariaceae).

Scrophularia umbrosa is a medicinal plant used as a traditional herb. This study was designed to investigate the phytochemical analysis of methanol (MeOH), DCM, and n-Hexane extracts of rhizome as well as total phenol and total flavonoid contents (TPC and TFC). In-vitro ß-hematin formation assay and DPPH method were applied for analyzing antimalarial and free-radical scavenging activities of the extracts, respectively. The formation of hemozoin has been proposed as an ideal drug target for antimalarial screening programs. The results showed that n-hexane and MeOH extracts of rhizome had no significant inhibitory effect on heme biocrystallization whereas the DCM extract of rhizome showed moderate antimalarial activity in comparison with chloroquine. GC-MS data showed that volatile portions of DCM and n-Hexane extracts from Scrophularia umbrosa (S. umbrosa) contained a few identifiable compounds. Moreover, fractions 20% and 40% MeOH-Water of MeOH extract of S. umbrosa displayed moderate to strong free radical scavenging activity which showed a positive relation between phenolic and flavonoid contents and free radical scavenging activity. Based on the results, the fractions of MeOH extract were evaluated by 1HNMR for predicting the groups of natural compounds and interfacing of chemical and biological assessments.

Antimalarial Activity of Plant Metabolites.

Malaria, as a major global health problem, continues to affect a large number of people each year, especially those in developing countries. Effective drug discovery is still one of the main efforts to control malaria. As natural products are still considered as a key source for discovery and development of therapeutic agents, we have evaluated more than 2000 plant extracts against Plasmodium falciparum. As a result, we discovered dozens of plant leads that displayed antimalarial activity. Our phytochemical study of some of these plant extracts led to the identification of several potent antimalarial compounds. The prior comprehensive review article entitled “Antimalarial activity of plant metabolites” by Schwikkard and Van Heerden (2002) reported structures of plant-derived compounds with antiplasmodial activity and covered literature up to the year 2000. As a continuation of this effort, the present review covers the antimalarial compounds isolated from plants, including marine plants, reported in the literature from 2001 to the end of 2017. During the span of the last 17 years, 175 antiplasmodial compounds were discovered from plants. These active compounds are organized in our review article according to their plant families. In addition, we also include ethnobotanical information of the antimalarial plants discussed.

In vivo antiplasmodial activity evaluation of the leaves of Balanites rotundifolia (Van Tiegh.) Blatter (Balanitaceae) against Plasmodium berghei.

Balanites rotundifolia (BR) (Van Tiegh.) Blatter (Balanitaceae) has been used in Ethiopian folk medicine to treat malaria, despite the lack of scientific validation. Therefore, the present study was carried out to evaluate the antiplasmodial activity of 80% methanol leaf extract of BR in mice. Both the 4-day suppressive test and Rane's test were employed. Three extract doses (BR100 mg/kg, BR200 mg/kg, and BR400 mg/kg/d) were given orally, and chloroquine was the standard drug administered through the same route. Outcome measures for evaluating antiplasmodial efficacy were parasitemia level, packed cell volume, survival time, and body temperature as well as body weight change. Moreover, preliminary phytochemical and acute toxicity studies were carried out. With the 4-day suppressive test, BR demonstrated dose-dependent significant reduction in parasitemia level at all test doses compared to the negative control: BR400 (67%, P<0.001), BR200 (42%, P<0.01), and BR100 (37%, P<0.05). With Rane's test as well, BR significantly (P<0.001 for all test doses) reduced the parasitemia level by 38% (BR100), 45% (BR200), and 69% (BR400) in comparison to vehicle treatment. The crude extract was estimated to have oral median lethal dose higher than 2,000 mg/kg, and the presence of alkaloids and cardiac glycosides was confirmed. Therefore, this study for the first time validated the antiplasmodial activity of crude leaf extract of BR. Further investigations for isolating specific phytochemicals and elucidating mechanisms are needed to address the quest for novel antimalarial drugs.