Actividad antiplasmodial de plantas usadas en la medicina tradicional contra la malaria en Cuba / Antiplasmodial activity of plant species used in traditional medicine for the control of malaria in Cuba

Introducción: Las plantas utilizadas en la medicina tradicional se exploran internacionalmente como fuentes valiosas de nuevos agentes antipalúdicos. Objetivos: Evaluar la actividad inhibidora in vitro frente a Plasmodium berghei de extractos de 27 especies de plantas utilizadas en el siglo pasado contra la malaria en Cuba, valorando los precedentes de estudios científicos de estas especies. Métodos: Se prepararon extractos etanólicos de 27 especies de plantas que se evaluaron in vitro a través de la inhibición de la esquizogonia de P. berghei ANKA. Se realizó una revisión basada en la consulta de artículos científicos para la clasificación de actividad basada en rangos de CI50. Resultados: Dieciséis especies mostraron precedentes de actividad inhibidora in vitro o su utilización en la medicina tradicional de otros países; siete especies no mostraron actividad coincidente. Solamente los extractos hidroalcohólicos de Euphorbia tithymaloides L. (partes aéreas) y Swietenia mahagoni (L.) Jacq. (corteza) fueron activos con CI50 ≤ 5 µg/mL, mientras para Colubrina arborescens (Mill.) Sarg. (corteza), la CI50 fue 14,3 ± 1,9 µg/mL. Extractos de 11 especies se probaron por el interés de su utilización en Cuba, sin precedentes etnobotánicos y experimentales disponibles. Entre estos, las partes aéreas de Baccharis halimifolia L. var. angustior DC; y de Oxandra lanceolata (Sw.) Baill. constituyeron fuentes antiplasmodiales de valores moderados de CI50. El resto de los extractos no fueron activos. Conclusiones: Estos resultados apoyan el uso en medicina tradicional en Cuba contra malaria de E. tithymaloides, S. mahagoni, C. arborescens, B. halimifolia y O. lanceolata, lo cual estimula a ampliar su estudio.

Introduction: Plants used in traditional medicine are studied worldwide as valuable sources of new antiplasmodial agents. Objective: To evaluate the in vitro inhibitory activity against Plasmodium berghei of extracts from 27 plant species used in the last century against malaria in Cuba and assess the previous scientific studies on these species. Methods: Ethanolic extracts from 27 plant species were prepared and evaluated in vitro by inhibiting the schizogony of P. berghei ANKA. A review of scientific papers was conducted to classify the activity based on IC50. Results: Sixteen species showed precedents of inhibitory activity in vitro or of their use in traditional medicine in other countries; seven species did not show coincident activity. Only hydroalcoholic extracts from Euphorbia tithymaloides L. (aerial parts) and Swietenia mahagoni (L.) Jacq. (bark) displayed activity at IC50 ≤ 5 µg/mL, while for Colubrina arborescens (Mill.) Sarg. (bark) IC50 was 14.3 ± 1.9 µg/mL. Extracts from 11 species, with no ethnobotanical and experimental precedents available, were evaluated given the interest of their use in Cuba. Of these species, the aerial parts of Baccharis halimifolia L. var. angustior DC and Oxandra lanceolata (Sw.) Baill. constituted antiplasmodial sources of moderate IC50 values. The rest of the extracts were not active. Conclusions: These results support the use of E. tithymaloides, S. mahagoni, C. arborescens, B. halimifolia y O. lanceolata in traditional medicine against malaria in Cuba, which stimulate further studies.

Steroids from Diplazium esculentum: Antiplasmodial activity and molecular docking studies to investigate their binding modes

@#Diplazium esculentum is an edible fern commonly consumed by the local community in Malaysia either as food or medicine. Isolation work on the ethyl acetate extract of the stem of D. esculentum resulted in the purification of two steroids, subsequently identified as stigmasterol (compound 1) and ergosterol5,8-endoperoxide (compound 2). Upon further testing, compound 2 displayed strong inhibitory activity against the Plasmodium falciparum 3D7 (chloroquine-sensitive) strain, with an IC50 of 4.27±1.15 µM, while compound 1 was inactive. In silico data revealed that compound 2 showed good binding affinity to P. falciparum-Sarco endoplasmic reticulum calcium-dependent ATPase (PfATP6); however, compound 1 did not show an antiplasmodial effect due to the lack of a peroxide moiety in the chemical structure. Our data suggested that the antiplasmodial activity of compound 2 from D. esculentum might be due to the inhibition of PfATP6, which resulted in both in vitro and in silico inhibitory properties.

Antiplasmodial activity of silver nanoparticles: A novel green synthesis approach

Objective: To synthesize silver nanoparticles using silver nitrate by a green technique which involves different compositions of aqueous leaf extracts of Azadirachta indica (neem) and Ocimum sanctum (tulsi). Methods: Their shape and size were determined using transmission electron microscopy and UV-visible spectroscopy. Their antiplasmodial activity was studied using the malarial parasite strain (Plasmodium falciparum, 3D7). The parasite strain (3D7) was collected and revived in vitro using Trager and Jensen method in RPMI 1640 medium for 7-8 cycles. Half maximal effective concentration values were calculated by nonlinear regression analysis. Results: Transmission electron microscopy results confirmed the formation of silver nanoparticles with size ranging from 4.74-39.32 nm and their size differs by varying the concentrations from 20% to 100% of neem extract in neem and tulsi extracts. It was observed that samples B and C showed half maximum effective concentration of about 0.3 μ M. Conclusions: It can be easily established that the aqueous leaf extracts of neem and tulsi in combination can be a good source for synthesis of silver nanoparticles with small size possessing appreciable antiplasmodial activity.

Antiplasmodial activity of silver nanoparticles: A novel green synthesis approach

Objective: To synthesize silver nanoparticles using silver nitrate by a green technique which involves different compositions of aqueous leaf extracts of Azadirachta indica (neem) and Ocimum sanctum (tulsi). Methods: Their shape and size were determined using transmission electron microscopy and UV-visible spectroscopy. Their antiplasmodial activity was studied using the malarial parasite strain (Plasmodium falciparum, 3D7). The parasite strain (3D7) was col ected and revived in vitro using Trager and Jensen method in RPMI 1640 medium for 7-8 cycles. Half maximal effective concentration values were calculated by nonlinear regression analysis. Results: Transmission electron microscopy results confirmed the formation of silver nanoparticles with size ranging from 4.74-39.32 nm and their size differs by varying the concentrationsfrom20％to100％ofneemextractinneemandtulsiextracts.Itwasobservedthat samples B and C showed half maximum effective concentration of about 0.3μM. Conclusions:It can be easily established that the aqueous leaf extracts of neem and tulsi in combination can be a good source for synthesis of silver nanoparticles with smal size possessing appreciable antiplasmodial activity.

Actividad anti-plasmodial de especies de Solanaceae presentes en Cuba / Antiplasmodial activity of Solanaceae species present in Cuba

Introducción: el control de la malaria depende en gran medida de una terapia efectiva. Muchos de los anti-maláricos actuales son de origen natural. Especies de la flora cubana contienen metabolitos anti-Plasmodium. En este estudio, se identifican extractos de Solanaceae con actividad antiplasmodial promisoria. Objetivo: evaluar la actividad esquizonticida frente a Plasmodium berghei de 31 extractos de 7 especies, correspondientes a 5 géneros de plantas de Solanaceae, colectadas en el occidente de nuestro país y sin antecedentes de un estudio similar. Métodos: se prepararon 31 extractos hidroalcohólicos (90 y 30 por ciento etanol) de diferentes órganos de: Brunfelsia undulata Sw., Datura stramonium L. var. tatula (L.) Torr., Physalis solanaceus (Schltdl.) Axelius, Solandra longiflora Tuss., Solanum myriacanthum Dunal, Solanum seaforthianum And. ySolanum umbellatum Mill.La actividad de los extractos se evaluó in vitro frente a P. berghei y se determinó su citotoxicidad frente a fibroblastos humanos MRC-5. Resultados: los extractos deB. undulata y S. umbellatumfueron inactivos.El extracto de tallos de S. seaforthianummostró la actividad antiplasmodial más potente (CI50 = 3,9µg/mL) con excelentes electividad (18,2). Conclusiones: se demostró la actividad anti-plasmodial in vitro de extractos de cinco especies de Solanaceae sin antecedentes de esta acción farmacológica. Se identificó un extracto con potente actividad esquizonticida frente a P. berghei y con excelente selectividad. Este resultado nos anima a continuar el estudio de la preparación vegetal de S. seaforthianum(AU)

Antiplasmodial activity of traditional polyherbal remedy from Odisha, India: Their potential for prophylactic use

Objective: To evaluate the potential prophylactic activity of traditional polyherbal remedy against malaria. Methods: A traditional polyherbal remedy against malaria from Odisha, India was evaluated for its potential prophylactic activity using in vitro hepatic cell lines assay and the murine malaria system Plasmodium yoelii yoelii/Anopheles stephensi. Results: The polyherbal extract inhibited the Plasmodium yoelii hepatic stages in vitro (IC

Antiplasmodial activity of traditional polyherbal remedy from Odisha, India:Their potential for prophylactic use

Objective: To evaluate the potential prophylactic activity of traditional polyherbal remedy against malaria. Methods: A traditional polyherbal remedy against malaria from Odisha, India was evaluated for its potential prophylactic activity using in vitro hepatic cell lines assay and the murine malaria system Plasmodium yoelii yoelii/Anopheles stephensi. Results: The polyherbal extract inhibited the Plasmodium yoelii hepatic stages in vitro (IC50 0.74 mg/mL), a therapeutic index of 9.54. In mice treated with the aqueous extract (2 000 mg/kg/day), peak parasitaemia values were 81% lower in the experimental 2.35% ± 0.14% as compared to controls 12.62% ± 0.52% (P Conclusions: The observations provide a proof of concept for a traditional malaria prophylactic remedy used by tribal populations in India.

Antiplasmodial Activity of the Root Extracts of Cochlospermum tinctorium in Mice Experimentally Infected with Clinical Isolates of Plasmodium berghei berghei (NK 65).

Aims: To determine in vivo the antiplasmodial activity of two chromatographic fractions obtained from Cochlospermum tinctorium A. Rich root bark extract against Plasmodium berghei berghei in mice. Methodology: Two chromatographic fractions were obtained from the crude methanolic extract of C. tinctorium root bark using petroleum ether (Fraction 1) and ethanol (Fraction 2) which were tested to determine their antiplasmodial activity in Swiss Albino mice infected with P. berghei berghei. Fraction 1 was administered at dose levels of 50, 100 and 200mg/kg/day, while fraction 2 was administered at dose levels of 25, 50 and 100 mg/kg/day. Chloroquine at 5 mg/kg per day was used as positive control and 0.2 ml normal saline was applied per day as sham. Results: Fraction 1had a percentage antiplasmodial activity of 80.67%, 64.14% and 69.71% for the dose level of 50, 100 and 200 mg/kg respectively. Data shows that fraction 1 treatment was not dose dependent as the lowest dosage of 50 mg/kg/day produced the highest percentage antiplasmodial activity of 80.67%, while 5 mg/kg chloroquine gave 100% cure. The effects of all treatments were significantly different (p<0.05). Fraction 2 produced a dose dependent antiplasmodial activity of 62.42%, 65.70% and 98.17% in infected mice treated with 25, 50 and 100 mg/kg/day of the fraction respectively in direct proportion. Only the 100 mg/kg fraction antiplasmodial activity was not significantly different (p>0.05) from that of 5 mg/kg chloroquine. The Median survival time post infection for infected mice treated with sham was 11 days, for infected mice treated with 50, 100 and 200mg/kg of fraction 1, the median survival time was 15.5, 15.5 and 19 days respectively, the log-rank (Mantle-Cox) test value of p<0.05 showed that survival curves are significantly different. The median survival time post infection for mice treated with 0.2ml normal saline per day was 11days, for mice treated with 25, 50 and 100mg/kg of fraction 2 the median survival time post infection was 19, 18.5 and 18 days respectively, Log-rank (Mantle-Cox) test value of p<0.05 indicates that survival curves are significantly different. The high antiplasmodial activity of 100 mg/kg fraction 1 was countered by its low survival time indicating a probable increase in toxicity to the mice with increase in dosage. The mean Packed Cell Volume (PCV) for infected mice treated with 50, 100 and 200 mg/kg fraction 1, the mean PCV was 36.83%, 32.42% and 37.96% respectively, while infected mice treated with25, 50 and 100mg/kg the mean PCV was 40.22%, 27.50% and 43.04% respectively. Since the mean PCV for infected mice treated with sham was 29.50%and 43.40% for 5mg/kg chloroquine treated mice, both fractions of C. tinctorium possess anaemia ameliorating property. However, only that of 25 and 100 mg/kg fraction 2 were the same as that of 5 mg/kg chloroquine (p>0.05).There was however no significant difference (p>0.05) in the mean percentage antiplasmodial activity of fraction 2 (65.26%) which was higher than that of fraction 1 (62.90%). Conclusion: C. tinctorium root bark extractpossess antimalarial and anaemia ameliorating properties which validates its use in traditional medicine for the treatment of malaria.

Actividad antiplasmódica in vitro de Piper holtonii (cordoncillo) / In vitro antiplasmodial activity of Piper holtonii (cordoncillo)

Introducción: especies vegetales del género Piper (Piperaceae) han sido usadas en la medicina tradicional en diferentes regiones del mundo, incluida Latinoamérica para el tratamiento de enfermedades tropicales como la malaria. Objetivo: evaluar la actividad antiplasmódica del extracto etanólico y las fracciones de diferente polaridad de Piper holtonii C.DC. Métodos: la actividad antiplasmódica del extracto etanólico de las partes aéreas de Piper holtonii y de las fracciones hexánica, clorofórmica, metanólica, butanólica y acuosa, se evaluó sobre un cultivo de Plasmodium falciparum cepa FCB-2. Se determinó la actividad hemolítica y se caracterizaron fitoquímicamente cada una de las fracciones. Resultados: el extracto etanólico y las fracciones de baja polaridad presentaron actividad promisoria con valores de CI50 inferiores a 25 µg/mL. Conclusiones: los resultados de la actividad biológica de Piper holtonii permiten sugerir que los metabolitos de baja y media polaridad están relacionados con la actividad antiplasmódica de esta especie.

Introduction: plant species of the genus Piper (Piperaceae) have been used in traditional medicine in various regions of the world. In Latin America they have been used to treat tropical diseases such as malaria. Objective: evaluate the antiplasmodial activity of the ethanolic extract and fractions of varying polarity of Piper holtonii C. DC. Methods: evaluation was conducted of the antiplasmodial activity of ethanolic extract from aerial parts of Piper holtonii and of hexane, chloroform, methanol, buthanol and aqueous fractions on a Plasmodium falciparum strain FCB-2 culture. Hemolytic activity was determined and phytochemical characterization of each fraction was performed. Results: both the ethanolic extract and the low-polarity fractions displayed promising activity, with CI50 values below 25 µg/mL. Conclusions: results concerning the biological activity of Piper holtonii suggest that low- and medium-polarity metabolites are related to antiplasmodial activity in this species.

Cuantificación de quinina en extractos de Cinchona pubescens y evaluación de la actividad antiplasmodial y citotóxica / Quantification of quinine in extracts from stems Cinchona pubescens and evaluation of antiplasmodial and cytotoxic activity

Plants belonging to the genus Cinchona L. (Rubiaceae), whose active ingredient is quinine, was used for centuries to treat malaria. Plants of this genus are a potential source of new structural templates in the search for new antimalarial candidates. This study aimed to the identification, quantification of quinine and other metabolites present in extracts of different polarity of the stems of Cinchona pubescens Vahl. , oxoquinovic acid isolation, antiplasmodial activity, and measuring its cytotoxic effect. The results show a high activity to antiplasmodial alkaloids extract (IC50 = 2.20 +/- 0.0325 ug/mL), cytotoxicity (CC50 = 80.2 +/- 12.2 ug/mL), and a quinine content of 21.3+/-0.0247 ppm. The compound known as acid antiplasmodial activity oxoquinovic presented in IC50 = 11.3 +/- 0.741 ug/mL, and cytotoxicity CC50 = 72.4 +/- 3.85 ug/mL. These results motivate phytochemical studies in the search for active structural analogues quinine and quinolinic core as a source of new antimalarial agents.

Las plantas pertenecientes al género Cinchona L. (familia Rubiaceae), cuyo principio activo es la quinina, fueron utilizadas durante siglos para tratar la malaria. Este género es una fuente potencial de nuevas plantillas estructurales en la búsqueda de nuevos candidatos antimaláricos. El presente trabajo tuvo como objetivo la identificación y, cuantificación de la quinina y de otros metabolitos presentes en los extractos de diferente polaridad, de los tallos de Cinchona pubescens Vahl. , el aislamiento del ácido oxoquinóvico, la actividad antiplasmodial y, además, la medición de su efecto citotóxico. Los resultados muestran una alta actividad antiplasmodial para el extracto de los alcaloides (IC50 = 2,20 +/- 0,0325 ug/mL), una baja citotoxicidad (CC50 = 80,2 +/- 12,2 ug/mL), y un alto contenido de quinina el cual fue 21,3+/-0,0247 ppm. El compuesto ácido oxoquinóvico presentó una actividad antiplasmodial de IC50 = 11,3 +/- 0.741 ug/mL, y una citotoxicidad de CC50 = 72,4 +/- 3,85 ug/mL. Estos resultados motivan los estudios fitoquímicos en la búsqueda de principios activos y análogos estructurales en diferentes especies de Cinchonas como una fuente de nuevos agentes antimaláricos.

In vivo Efficacy and Toxicity Studies on Erythrina senegalensis and Khaya ivorensis Used as Herbal Remedies for Malaria Prevention in Cameroon.

Aim: The study aimed at assessing the in vivo anti-plasmodial activity of aqueous extracts from Erythrina senegalensis and Khaya ivorensis, two plants used traditionally as bark decoctions in Cameroon to prevent and cure malaria. Methodology: The antiplasmodial activity of aqueous extracts of E. senegalensis and K. ivorensis was investigated using a murine malaria model (Plasmodium berghei / Anopheles stephensi / BALB/c mice), applying a protocol for assessing the prophylactic potential of the remedy. Treatments were administered orally to BALB/c mice for 9 days at doses of 200 and 400 mg/kg/day. Mice were challenged on day 3 of treatment by exposure to P. berghei infected mosquitoes. The impact on parasitaemia was assessed on thin blood smears prepared on day 7 after exposure to infective bites. The acute toxicity of the plant extracts was tested according to the guidelines of the Organization for Economic Co-operation and Development (OECD guidelines 423). Results: The plant extracts showed antiplasmodial activity, reducing parasitaemia by 40.4% to 56.3%, according to the extract. In particular, a combination of the two extracts at the dose of 100 mg/kg each provided a reduction of parasitaemia in treated mice by more than 50%, as compared to controls. The extract of E. senegalensis when used alone at 200 mg/kg/day reduced the parasitaemia by 40.3% +/- 7.2%, doubling the dosage increased parasite suppression to 56.3% +/- 5.1%. Toxicity studies yielded comforting results: up to a dosage of 2000 mg/kg no mortality occurred in treated mice. Also, animals treated during the antiplasmodial experiments did not reveal signs of toxicity and remained in good conditions up to the end of the experiments. Conclusion: The results suggest that the combination of E. senegalensis and K. ivorensis could be a valid plant combination for the preparation of a standardized, effective and affordable remedy against malaria, in particular for Cameroonian communities with limited access to modern drugs.

Antiplasmodial Activity of Aqueous leaf Extract of Mucuna Pruriens Linn in Mice Infected with Plasmodium Berghei (Nk-65 Strain).

The antiplasmodial activity of the aqueous leaf extract of Mucuna pruriens (M. pruriens) was evaluated against Plasmodium berghei NK-65 strain in mice. The plant was selected based on their traditional claims for treatment of fever and other malaria related diseases in southeastern region of Nigeria. An aqueous leaf extract (90 – 270 mg/kg) was investigated for antiplasmodial activity against Chloroquine-sensitive Plasmodium berghei infections in mice. The antiplasmodial activity during early and established infections as well as prophylactic action of the plant in blood was investigated. Chloroquine (10 mg/kg) and pyrimethamine (1.2 mg/kg) were used as positive controls. The extract (90 – 270 mg/kg) dose dependently reduced parasitaemia induced by Chloroquine sensitive Plasmodium berghei infection in suppressive, prophylactic and curative models in mice. The extract at these doses caused 60.06 – 71.75% inhibition of parasitaemia in the suppressive test, 65.97 – 84.38% parasitaemia inhibition in prophylactic test and a mean survival time of 16 – 30 days representing 64.41– 89.71% inhibition of parasitaemia in the curative test. These reductions were statistically significant (P<0.05) comparable to that of the standard drug used (Chloroquine and Pyrimethamine). These results show that the aqueous leaf extract of M. pruriens possesses significant (P<0.05) antiplasmodial activity which confirms its use in folkloric medicine in the treatment of fever and other malaria-related disease.

Evaluation of the Larvicidal, Antiplasmodial and Cytotoxicity Properties of Cassia arereh Del. Stem Bark.

Aims: The present study was carried on the stem bark of Cassia arereh Del. Different extracts were prepared and were assessed for their in vitro larvicidal, antiplasmodial and cytotoxicity properties. Methodology: Larvicidal activity of the methanol extract was evaluated against 3rd instar larvae of Culex quinquefasciatus using method recommended by World Health Organization. The antimalarial activity of chloroform, ethyl acetate, methanol and aqueous extracts was assessed on the chloroquine-resistant strain W2 strain of Plasmodium falciparum by flow cytometry. Cytoxicity effect was assessed on two human cell lines K562S (by flow cytometry) and HepG2 (by MTT assay). Results: The larvicidal activities of different concentrations of C. arereh stem bark methanolic extract after 24 h of incubation revealed that the 1.0 g/L concentration gave the highest mortality (40.2%). lethal concentrations that killed 25% (LC25), 50% (LC50), 90% (LC90) and 95% (LC95) of larvae in 24 h were 4235, 8230, 16007, 29325 and 40680 ppm. The best antimalarial activities were detected in the chloroform extract with IC50 > 12.5 μg/ mL and cytotoxicity effect with IC50 > 12.5 μg/ mL on both K562S and HepG2 cell lines indicative of promising security index. Phytochemical screening indicated the presence of anthraquinones, flavanoids, terpenes, steroles and tannins. Conclusion: This result indicates that C. arereh stem bark could be a good source of bioactive ingredients.

Actividad antiplasmodial y citotóxica de extractos etanólicos de especies de género Piper / Antiplasmodial and cytotoxic activity of ethanol extracts of species of the genus Piper

Plasmodium resistance to antimalarial drugs has expanded and intensified, making urgent new and effective antimalarials. The aim of this study was to evaluate the antiplasmodial and cytotoxic activity of Piper aduncum L, Piper auritum Kunth, Piper jericoense Trel. & Yunck, Piper obrutum Trel. & Yunck, Piper marginatum Jacq collected in Antioquia, Colombia. The results of antiplasmodial activity (IC50) ranged between 26.5 and 50 ug/mL and cytotoxicity (CC50) between 8.67 and 100 ug /mL. We conclude that moderate activity antiplasmodial and was low cytotoxic activity for extracts of the genus Piper species evaluated.

La resistencia de Plasmodium a los medicamentos antimaláricos se ha expandido e intensificado, lo que hace urgente nuevos y efectivos antimaláricos. El objetivo de este trabajo fue la evaluación de la actividad antiplasmodial y citotóxica de Piper aduncum L., Piper auritum Kunth, Piper jericoense Trel. & Yunck., Piper obrutum Trel. & Yunck., Piper marginatum Jacq. Colectadas en Antioquia, Colombia. Los resultados de actividad antiplasmodial (IC50) oscilaron entre 26,5 y 50 ug/mL y de citotoxicidad (CC50) entre 8,67 y 100 ug/mL. Se concluye que se obtuvo moderada actividad antiplasmodial y baja actividad citotóxica para los extractos de las especies evaluadas de género Piper.

In vitro antiplasmodial effect of ethanolic extracts of coastal medicinal plants along Palk Strait against Plasmodium falciparum

Objective: To identify the possible antiplasmodial compounds from Achyranthes aspera (A. aspera), Acalypha indica (A. indica), Jatropha glandulifera (J. glandulifera) and Phyllanthusamarus (P. amarus). Methods: The A. aspera, A. indica, J. glandulifera and P. amarus were collected along Palk Strait and the extraction was carried out in ethanol. The filter sterilized extracts (100, 50, 25, 12.5, 6.25 and 3.125 μg/mL) of leaf, stem, root and flower extracts of A. aspera, A. indica, J. glandulifera and P. amarus were tested for antiplasmodial activity against Plasmodiumfalciparum. The potential extracts were also tested for their phytochemical constituents. Results:Of the selected plants species parts, the stem extract of A. indica showed excellent antiplasmodial activity (IC50= 43.81μg/mL) followed by stem extract of J. glandulifera (IC50= 49.14μg/mL). The stem extract of A. aspera, leaf and root extracts of A. indica, leaf, root and seed extracts of J.glandulifera and leaf and stem extracts of P. amarus showed IC 50 values between 50 and 100 μg/mL. Statistical analysis revealed that, significant antiplasmodial activity (P<0.01) was observed between the concentrations and time of exposure. The chemical injury to erythrocytes was also carried out and it showed that there were no morphological changes in erythrocytes by the ethanolic extract of all the tested plant extracts. The in vitro antiplasmodial activity might be due to the presence of alkaloids, glycosides, flavonoids, phenols, saponins, triterpenoids, proteins, and tannins in the ethanolic extracts of tested plants. Conclusions: The ethanolic stem extracts of P. amarus and J. glandulifera possess lead compounds for the development of antiplasmodial drugs.

Antiplasmodial and antiulcer activities of Melanthera scadens

<p><b>OBJECTIVE</b>To evaluate the antimalarial and antiulcerogenic activities of leaf extract and fractions of Melanthera scandens (M. scandens).</p><p><b>METHODS</b>The crude leaf extract (37-111 mg/kg) and fractions (chloroform, ethylacetate and methanol; 78 mg/kg) of M. scadens were investigated for antiplasmodial activity against chloroquine-sensitive Plasmodium berghei infections in mice and for antiulcer activity against experimentally-induced ulcers. The antimalarial activity during early and established infections as well as prophylactic was investigated. Artesunate (5 mg/kg) and pyrimethamine (1.2 mg/kg) were used as positive controls. Thin films made from tail blood of each mouse were used to assess the level of parasitaemia of the mice. Antiulcer activity of the crude extract was also evaluated against indomethacin, ethanol and histamine induced ulcers.</p><p><b>RESULTS</b>The extract and its fractions dose-dependently reduced parasitaemia induced by chloroquine-sensitive Plasmodium berghei infection in prophylactic, suppressive and curative models in mice. These reductions were statistically significant (P<0.001). They also improved the mean survival time (MST) from 9.28 to 17.73 days as compared with the control (P<0.01-0.001). The activities of extract/fractions were incomparable to that of the standard drugs i.e. artesunate and pyrimethamine. On experimentally-induced ulcers, the extract inhibited indomethacin, ethanol and histamine induced ulcers. These inhibitions were statistically significant (P<0.001) and in a dose-dependent fashion.</p><p><b>CONCLUSIONS</b>The antiplasmodial and antiulcerogenic effects of this plant may in part be mediated through the chemical constituents of the plant.</p>

In vitro antiplasmodial activity of marine sponge Hyattella intestinalis associated bacteria against Plasmodium falciparum

Objective: To identify the antiplasmodial drugs from the marine sponge Hyattella intestinalis (H. intestinalis) associated bacteria. Methods: The H. intestinalis samples were collected from Thondi coast and subjected for enumeration and isolation of associated bacteria. Filter sterilized extracts (100, 50, 25, 12.5, 6.25 and 3.125μg/mL) from bacterial isolates were screened for antiplasmodial activity against P. falciparum and potential extracts were also screened for biochemical constituents. Results: The count of THB isolates were maximum in November 2007 (20×10 4 CFU/g) and the average count was maximum during the monsoon season (77×103 CFU/g). A total of 29 bacteria were isolated based on the morphological characteristics and screened for antiplasmodial activity. The antiplasmodial activity of THB20 extract (IC50 41.88 μg/mL) showed at two fold concentration of IC50 value of the positive control chloroquine (IC50 19.59 μg/mL) and 14 bacterial isolates showed IC50 value of more than 100 μg/mL. Statistical analysis reveals that, significant in vitro antiplasmodial activity (P<0.05) was observed between the concentrations and time of exposure. The chemical injury to erythrocytes showed no morphological changes in erythrocytes by the ethyl acetate extract of THB isolates after 48 h of incubation. The antiplasmodial activity of potential bacterial isolates might be due to the presence of sugars and alkaloids in the ethyl acetate extracts. Conclusions: It is concluded from the present study that, the ethyl acetate extracts of THB20 posses novel metabolites for the development of newer antiplasmodial drugs.

In vitro Antiplasmodial Activity and Cytotoxicity of Ten Plants Used as Traditional Medicine in Malaysia / Jurnal Sains Kesihatan Malaysia

Dichloromethane and methanolic extracts of each plant were tested for their antiplasmodial activity on chloroquineresistant strain of Plasmodium falciparum (FCB strain), based on lactate dehydrogenase activity. Cytotoxicity was assessed with the MTT test on MRC-5 human diploid embryonic lung cells. Most extracts of ten selected plants used in Malay traditional medicine in Malaysia had activity in vitro. This supports continued investigations of traditional medicine in the search for new antimalarial agent. The compounds responsible for the observed antiplasmodial effects are under investigation.

Plant-Derived Antimalarial Agents: From Crude Extracts To Isolated Bioactive Compounds

Despite decades of intense research, malaria remains a deadly disease of the developing worlds. Drugresistance to limited available antimalarials, in part, has contributed to the persistence of this infectious disease. Likewise, the use of antimalarials such as artemisinin, though effective in global malaria control programs, is hampered by high cost and limited supply. Therefore, identification of an antimalarial drug that is easy to isolate and produce, inexpensive, and demonstrates little toxicity across a diverse population represents the ideal agent needed for global malaria control programs and eradication of this deadly disease. This review discusses several antimalarial compounds containing unique structural composition that have been isolated and characterized from plant sources. These compounds have exhibited promising antimalarial activities in vitro and in vivo. However, limitations such as toxicity, low bioavailability and/or poor solubility have probably restricted the scope of use for several plant products in humans. Nevertheless, plants provide novel leads, which can be developed into safe drugs by synthetic strategies as exemplified by artemether and quinoline class of antimalarials. Therefore, plant bioactive compounds described herein provide useful alternatives, which could be modulated to obtain antimalarials active against not only drug-sensitive, but also drug-resistant and multi-drug resistant strains of Plasmodium. In this direction, semi synthetic approaches to newer and modified antimalarials have provided useful insights into their applicability in antimalarial drug discovery.

Estudo fitoquímico biomonitorado pelos ensaios de toxicidade frente à Artemia salina e de atividade antiplasmódica do caule de aninga (Montrichardia linifera) / Phytochemical study bioassay-guided by tests of toxicity on Artemia salina and antiplasmodial activity from stem of aninga (Montrichardia linifera)

Montrichardia linifera é uma planta aquática de amplo uso na medicina tradicional amazônica. Entretanto, muito pouco se conhece sobre a sua composição química, e sua atividade biológica ainda não foi comprovada. Na busca de substância(s) biologicamente ativa(s), este trabalho realizou um estudo fitoquímico biomonitorado no qual foram testados os extratos hexânico e etanólico obtidos do caule desta espécie, dos quais apenas o extrato etanólico foi selecionado para o fracionamento cromatográfico por ter apresentado toxicidade contra a Artemia salina e atividade contra o Plasmodium falciparum, parasita causador da malária. As atividades biológicas concentraram-se na fração diclorometânica que apresentou alta toxicidade contra A. salina (DL50<31µg mL-1) e alta atividade antiplasmódica (IC50<10 µg mL-1), mostrando promissora atividade antimalárica. Desta fração, o composto aromático p-hidroxibenzaldeído foi isolado pela primeira vez nesta planta.

Montrichardia linifera is an aquatic plant widely use in Amazon folkmedicine. However, very little is known about the chemical composition and biological activity. In search of biologically active (s) substance (s) phytochemical bioassay-guided study was conducted evaluating hexane extract and ethanol extract obtained from stems of this species. Since only the ethanol extract presented toxicity against Artemia salina and activity against Plasmodium falciparum, this extract was selected for chromatographic fractionation. The biological activities were concentred in dichloromethane fraction which showed high toxicity against A. saline (LD50< µg mL-1) and high antiplasmodial activity (IC50 <10 µg mL-1), showing promising antimalarial activity. Of this fraction, the aromatic compound p-hydroxybenzaldehyde was isolated for the first time in this plant.