Preparation, Standardization and Anti-plasmodial Efficacy of Novel Malaria Nosodes.

BACKGROUND: Resistance to artemisinin and its partner drugs has threatened the sustainability of continuing the global efforts to curb malaria, which urges the need to look for newer therapies to control the disease without any adverse side effects. In the present study, novel homeopathic nosodes were prepared from Plasmodium falciparum and also assessed for their in vitro and in vivo anti-plasmodial activity. METHODS: Three nosodes were prepared from P. falciparum (chloroquine [CQ]-sensitive [3D7] and CQ-resistant [RKL-9] strains) as per the Homeopathic Pharmacopoeia of India, viz. cell-free parasite nosode, infected RBCs nosode, mixture nosode. In vitro anti-malarial activity was assessed by schizont maturation inhibition assay. The in vitro cytotoxicity was evaluated by MTT assay. Knight and Peter's method was used to determine in vivo suppressive activity. Mice were inoculated with P. berghei-infected erythrocytes on day 1 and treatment was initiated on the same day. Biochemical, cytokine and histopathological analyses were carried out using standard methods. RESULTS: In vitro: the nosodes exhibited considerable activity against P. falciparum with maximum 71.42% (3D7) and 68.57% (RKL-9) inhibition by mixture nosode followed by cell-free parasite nosode (62.85% 3D7 and 60% RKL-9) and infected RBCs nosode (60.61% 3D7 and 57.14% RKL-9). The nosodes were non-toxic to RAW macrophage cell line with >70% cell viability. In vivo: Considerable suppressive efficacy was observed in mixture nosode-treated mice, with 0.005 ± 0.001% parasitemia on day 35. Levels of liver and kidney function biomarkers were within the normal range in the mixture nosode-treated groups. Cytokine analysis revealed increased levels of IL-4 and IL-10, whilst a decline in IL-17 and IFN-γ was evident in the mixture nosode-treated mice. CONCLUSION: The mixture nosode exhibited promising anti-malarial activity against P. falciparum and P. berghei. Biochemical and histopathological studies also highlighted the safety of the nosode for the rodent host. The study provides valuable insight into a novel medicament that has potential for use in the treatment of malaria.

Efficacy of Chininum Sulphuricum 30C against Malaria: An in vitro and in vivo Study.

BACKGROUND: New effective, economical and safe antimalarial drugs are urgently needed due to the development of multi-drug-resistant strains of the parasite. Homeopathy uses ultra-diluted doses of various substances to stimulate autoregulatory and self-healing processes to cure various ailments. The aim of the study was to evaluate the in vitro and in vivo antimalarial efficacy of a homeopathic drug, Chininum sulphuricum 30C. METHODS: In vitro antiplasmodial activity was screened against the P. falciparum chloroquine-sensitive (3D7) strain, and cell viability was assessed against normal human dermal fibroblasts and HepG2 cells. Suppressive, preventive and curative studies were carried out against P. berghei-infected mice in vivo. RESULTS: Chininum sulphuricum (30C) revealed good antiplasmodial activity in vitro, with 92.79 ± 6.93% inhibition against the 3D7 strain. The cell viability was 83.6 ± 0.6% against normal human dermal fibroblasts and 95.22 ± 5.1% against HepG2 cells. It also exhibited suppressive efficacy with 95.56% chemosuppression on day 7 with no mortality throughout the follow-up period of 28 days. It also showed preventive activity against the disease. Drug treatment was also safe to the liver and kidney function of the host as evidenced by biochemical studies. CONCLUSION: Chininum sulphuricum 30C exhibited considerable antimalarial activity along with safety to the liver and kidney function of the host.

Ethanol extract of Bergenia ciliata (Haw.) Sternb. (rhizome) impedes the propagation of the malaria parasite.

ETHNOPHARMACOLOGICAL RELEVANCE: The increasing resistant cases even against artemisinin-based combination therapy have necessitated the need to develop new antimalarials. Phytomedicinal therapy is a benchmark for malaria in the Himalayan region. As the dialect and traditional variations have been seen along with this, usage of medicinal plant, its portion (shoot and root system) and mode of preparation also varies. There is no scientific evidence available for illustrating the antiplasmodial activity of the rhizomes of Bergenia ciliata (Saxifragaceae), which is known to be an antipyretic (fever akin to malaria), hepato-protective, and also for spleen enlargement. AIM OF THE STUDY: The present study evaluates the antimalarial activity of ethanol extract of B. ciliata rhizomes (EREBC). MATERIALS AND METHODS: HPTLC was performed to identify and quantify three marker compounds in EREBC. The in vitro antimalarial activity was evaluated by schizont maturation inhibition assay. MTT assay was employed to test the cytotoxicity of EREBC. Peter's 4-day test and Peters method was employed to discern the suppressive and preventive activity of the extract respectively. RESULTS: HPTLC analysis revealed the presence of bergenin, epicatechin and gallic acid in the extract. EREBC exhibited considerable inhibition (IC50 < 5 µg/mL) of schizont maturation of both RKL-9 and MRC-2 strains of P. falciparum. EREBC was non-toxic to both HeLa cells and normal dermal fibroblasts (CC50 > 1000 µg/mL). The selectivity index was > 200 for both strains. Acute toxicity of EREBC was > 4 g/kg. EREBC exhibited considerable in vivo suppressive activity with 96.48% inhibition at 500 mg/kg in comparison to chloroquine (96.08%). The ED50 of the extract was < 50 mg/kg. No mortality was evident in mice administered with different doses of EREBC (50-500 mg/kg) throughout the follow up period of 28 days. EREBC exhibited safety to liver and kidney function of mice as observed from biochemical analysis. CONCLUSION: Overall, the study illustrates the marked efficacy and potential of EREBC as an antimalarial agent with bergenin, epicatechin and gallic acid its major constituents, which played a pivotal role in the generation of the immune response.

Antiplasmodial potential of Thalictrum foliolosum (Ranunculaceae) against lethal murine malaria.

BACKGROUND AND OBJECTIVES: The emergence of multi-drug resistant (MDR) strains of Plasmodium falciparum highlights the need to develop novel antimalarial drugs. Present study explores the in vivo antiplasmodial activity of ethanol leaf extract of Thalictrum foliolosum (ELETF) against lethal murine malaria. METHODS: The acute toxicity of the extract was assessed by Limit test of Lorke. The suppressive activity of the extract was evaluated by Peter's 4 day test. In vivo preventive and curative activity of ELETF was assessed by Peter's method and Ryley and Peter's method respectively. Biochemical assays were carried out using standard methods. RESULTS: ELETF (1000 mg/kg) exhibited considerable in vivo schizontocidal activity with 67.11% chemosuppression on Day 5. The ED50 of the extract was 579.56 mg/kg. ELETF also showed significant repository activity with 87.70% chemosuppression at 750 mg/kg, which was greater than pyrimethamine (78.78%). ELETF exhibited dose dependent chemosuppression in the curative test with maximum 70.06% chemosuppression (750 mg/kg). Maximum Mean Survival Time (MST) was 19.2±4.60 and 22.66±4.41 days respectively in the suppressive and curative test, which was extremely statistically significant (p<0.0005) in comparison to untreated control which died by Day 9 post inoculation. Biochemical analysis revealed the safety of ELETF to the hepatic and renal functions of the rodent host. INTERPRETATION & CONCLUSION: The study reports the antiplasmodial potential of Thalictrum foliolosum (ELETF) against Plasmodium berghei infection. The extract can be developed as a phytomedicine against malaria. Alternatively, the active components can be isolated as new lead compounds against the disease.

Anthelmintic potential of Calotropis procera, Azadirachta indica and Punica granatum against Gastrothylax indicus.

Anthelmintic activity of both ethanolic and aqueous extracts of Calotropis procera flowers, Azadirachta indica leaves and Punica granatum fruit peel in comparison with albendazole was evaluated through in vitro studies by the worm motility inhibition assay. Significant anthelmintic effects (p < 0.0005) were observed on live Gastrothylax indicus worm as evident from their mortality at 4 h post exposure to both ethanolic and aqueous extracts. Phytochemical analysis of extracts revealed the presence of phenols, alkaloids, saponins, tannins, flavonoids, steroids and triterpenoids. LC-50 values were determined to be 12.05 mg/ml ± 3.24 and 23.52 mg/ml ± 6.4 for C. procera, 24.37 mg/ml ± 4.11 and 21.02 mg/ml ± 4.6 for A. indica, 18.92 mg/ml ± 4.54 and 24.43 mg/ml ± 6.96 for P. granatum ethanolic and aqueous extracts respectively, whereas it was 29.23 µg/ml ± 4.51 for albendazole. The mean mortality index (MI) was 1.0 and 0.90 for C. procera, 0.90 for A. indica and 0.73 and 0.80 for P. granatum ethanolic and aqueous extracts respectively whereas for albendazole it was 1.0. Percent mean worm motility inhibition (%WMI) was observed to be between 70 and 100 % for different extracts.Various concentrations (5-5000 µg/ml) of all the plant extracts and albendazole were used to detect their cytotoxic effects against HeLa cell line to determine CC-50 by MTT assay. CC-50 values, of all the plant extracts were determined to be >1000 µg/ml and for albendazole it was found to be >10 µM. All the three plants can be potential sources for novel anthelmintics.

Antiplasmodial activity of aqueous extract of Berberis aristata roots against Plasmodium berghei-infected BALB/c mice.

CONTEXT: The rising problem of resistance to present antimalarial drugs stresses the need to look for newer antiplasmodial components with effective modes of action. The roots of Berberis aristata DC. (Berberidaceae) are used in the traditional medicine for malaria in various parts of India. OBJECTIVE: The objective of this study was to evaluate antiplasmodial activity of B. aristata roots extract for the validation of its traditional medicinal use. MATERIAL AND METHODS: Aqueous root extract of Berberis aristata (AREBA) was screened for its in vitro as well as in vivo antiplasmodial activity against lethal rodent malaria parasite Plasmodium berghei NK65. In vitro activity was evaluated against schizont maturation of P. berghei using various concentrations ranging from 1 to 100 µg/mL. For in vivo studies, AREBA at the doses of 150, 250, 350, and 650 mg/kg/d was administered to P. berghei infected BALB/c mice orally for 4 consecutive days (D0-D3). RESULTS: AREBA showed in vitro antiplasmodial activity with an IC50 value of 40 µg/mL. In vivo studies demonstrated a variable dose-dependent chemosuppression with higher efficacy at lower doses. At a dose of 350 mg/kg/d, the suppressive and preventive activities were found to be 67.1% and 53.9%, respectively, followed by enhancing mean survival period up to 12.8 d for the curative assay versus 7.5 d for the untreated mice. DISCUSSION AND CONCLUSION: These results provide relevant scientific evidences for the traditional medicinal use of this plant as malaria remedy and further advocates the isolation and characterization of active antiplasmodial principle from this plant.

Antimalarial efficacy of Albizia lebbeck (Leguminosae) against Plasmodium falciparum in vitro & P. berghei in vivo.

BACKGROUND & OBJECTIVES: Albizia lebbeck Benth. (Leguminosae) has long been used in Indian traditional medicine. The current study was designed to test antimalarial activity of ethanolic bark extract of A. lebbeck (EBEAL). METHODS: EBEAL was prepared by soxhlet extraction and subjected to phytochemical analysis. The extract was evaluated for its in vitro antimalarial activity against Plasmodium falciparum chloroquine (CQ) sensitive (MRC2) and CQ resistant (RKL9) strains. Cytotoxicity (CC 50 ) of extract against HeLa cells was evaluated. Median lethal dose (LD 50 ) was determined to assess safety of EBEAL in BALB/c mice. Schizonticidal (100-1000 mg/kg) and preventive (100-750 mg/kg) activities of EBEAL were evaluated against P. berghei. Curative activity (100-750 mg/kg) of extract was also evaluated. RESULTS: Phytochemical screening revealed presence of alkaloids, flavonoids, phenols, saponins, terpenes and phytosterols. The extract exhibited IC 50 of 8.2 µg/ml (MRC2) and 5.1 µg/ml (RKL9). CC 50 of extract on HeLa cell line was calculated to be >1000 µg/ml. EBEAL showed selectivity indices (SI) of >121.9 and >196.07 against MRC2 and RKL9 strains of P. falciparum, respectively. LD 50 of EBEAL was observed to be >5 g/kg. Dose-dependent chemosuppression was observed with significant ( p<0.001) schizonticidal activity at 1000 mg/kg with ED 50 >100 mg/kg. Significant (P<0.001) curative and repository activities were exhibited by 750 mg/kg concentration of extract on D7. INTERPRETATION & CONCLUSIONS: The present investigation reports antiplasmodial efficacy of EBEAL in vitro against P. falciparum as evident by high SI values. ED 50 of <100 mg/kg against P. berghei categorizes EBEAL as active antimalarial. Further studies need to be done to exploit its antiplasmodial activity further.

Antiplasmodial potential of homeopathic drugs Chelidonium and nosode against Plasmodium berghei infection.

BACKGROUND: Malaria remains a major global health concern in developing regions of the world. Homeopathy, a holistic system of medicine, has a lot to offer in protecting against malaria. METHODS: In the present study, antimalarial efficacy of combination of two homeopathic drugs Chelidonium 30 and nosode 30 has been evaluated in vivo against Plasmodium berghei (P. berghei) infection using Peters 4-day test. Biochemical assays have been performed to assess the levels of hepatic and renal function biomarkers upon drug treatment using diagnostic kits. RESULTS: The combination of the drugs demonstrated considerable in vivo antimalarial activity with chemosuppression of 91.45% on day 7. The combination also significantly (p < 0.0005) enhanced the mean survival time of mice which was calculated to be 22.5 ± 6.31 days, whereas it was 8.55 ± 0.83 days in infected control. The increase in levels of the liver function marker enzymes tested in serum of treated mice were significantly less (p < 0.0005) than those observed in infected control on day 10. The serum urea and creatinine used for assessment of renal sufficiency were slightly elevated above normal, but were statistically significant (p < 0.0005) as compared to infected control. CONCLUSIONS: The study establishes the effectiveness of the combination against P. berghei in vivo along with the safety of the drugs to the liver and kidney functions of the host.

Antimalarial activity of Bergenia ciliata (Haw.) Sternb. against Plasmodium berghei.

The emergence of resistance against most of the drugs in current use against malaria has aggravated the disease burden in endemic regions. Several plants species have been used for treatment of malaria in traditional/cultural health systems. Bergenia ciliata, used traditionally for treatment of fever by local communities in the Himalayan Region, was evaluated for its plausible role as an antimalarial. Phytochemical screening of the ethanolic leaf extract of B. ciliata (ELEBC) revealed the presence of phenols, flavonoids, steroids and diterpenes. The extract showed good in vitro antiplasmodial activity, with an IC50 <10 µg/ml. Acute toxicity of the extract was observed to be >5 g/kg, which is considered toxicologically safe for oral administration. When tested in vivo, different concentrations of the extract (250 to 1,000 mg/kg) exhibited considerable chemosuppression on day 7, in a dose-dependent manner. Maximum chemosuppression was observed to be 87.50% at 1,000 mg/kg. Administration of ELEBC (750 and 1,000 mg/kg) significantly (p < 0.0005) enhanced the mean survival time of mice in comparison to infected control, which exhibited a mean survival time of 8.6 ± 1.5 days. Study reports presence of considerable in vitro and in vivo antimalarial activity in ethanolic leaf extract of B. ciliata for first time. Hence, the ethnopharmacological usage of the plant for treating fever is confirmed with experimental evidence.

Anti-malarial property of steroidal alkaloid conessine isolated from the bark of Holarrhena antidysenterica.

BACKGROUND: In the face of chronic and emerging resistance of parasites to currently available drugs and constant need for new anti-malarials, natural plant products have been the bastion of anti-malarials for thousands of years. Moreover natural plant products and their derivatives have traditionally been a common source of drugs, and represent more than 30% of the current pharmaceutical market. The present study shows evaluation of anti-malarial effects of compound conessine isolated from plant Holarrhena antidysenterica frequently used against malaria in the Garhwal region of north-west Himalaya. METHODS: In vitro anti-plasmodial activity of compound was assessed using schizont maturation and parasite lactate dehydrogenase (pLDH) assay. Cytotoxic activities of the examined compound were determined on L-6 cells of rat skeletal muscle myoblast. The four-day test for anti-malarial activity against a chloroquine-sensitive Plasmodium berghei NK65 strain in BALB/c mice was used for monitoring in vivo activity of compound. In liver and kidney function test, the activity of alkaline phosphatase (ALP) was examined by p-NPP method, bilirubin by Jendrassik and Grof method. The urea percentage was determined by modified Berthelot method and creatinine by alkaline picrate method in serum of mice using ENZOPAK/CHEMPAK reagent kits. RESULTS: Compound conessine showed in vitro anti-plasmodial activity with its IC50 value 1.9 µg/ml and 1.3 µg/ml using schizont maturation and pLDH assay respectively. The compound showed cytotoxity IC50= 14 µg/ml against L6 cells of rat skeletal muscle myoblast. The isolated compound from plant H. antidysenterica significantly reduced parasitaemia (at 10 mg/kg exhibited 88.95% parasite inhibition) in P. berghei-infected mice. Due to slightly toxic nature (cytotoxicity = 14), biochemical analysis (liver and kidney function test) of the serum from mice after administration of conessine were also observed. CONCLUSION: The present investigation demonstrates that the compound conessine exhibited substantial anti-malarial property. The isolated compound could be chemically modified to obtain a more potent chemical entity with improved characteristics against malaria.

Antimalarial potential of China 30 and Chelidonium 30 in combination therapy against lethal rodent malaria parasite: Plasmodium berghei.

Homeopathy is a therapeutic method based on the application of similia principle, utilizing ultra-low doses of medicinal substances made from natural products. The present study has been designed to evaluate the efficacy of Cinchona officinalis (Chin.) 30C and Chelidonium majus (Chel.) 30C in combination therapy against lethal murine malaria. Five groups having twelve BALB/c mice each were administered orally with 0.2 ml/mouse/day of different drugs, and their antimalarial potential was evaluated by Peter's 4-day test. The combination of Chin. 30 and Chel. 30 exhibited complete parasite clearance by the 28th day post-inoculation which was similar to the positive control [artesunate (4 mg/kg)+sulphadoxine-primethamine (1.2 mg/kg)] group. Both the groups exhibited enhanced mean survival time (MST) 28±0 days,whereas, the mice of infected control group survived up to 7.6±0.4 days only. The preventive and curative activities of the combination in comparison to the positive controls [pyrimethamine (1.2 mg/Kg) and chloroquine (20 mg/Kg), respectively] were also evaluated. The combination had a significant preventive activity (p<0.0005), with 89.2% chemosuppression which was higher than the standard drug, pyrimethamine (83.8%). It also showed a moderate curative activity with complete clearance of parasite in 50% of surviving mice, and enhancing the MST of mice up to 26.8±2.8 days. These findings point to the significant antiplasmodial efficacy of the combination of these homeopathic drugs against Plasmodium berghei.

Antiplasmodial activity of Xanthium strumarium against Plasmodium berghei-infected BALB/c mice.

The present work was undertaken to evaluate the antiplasmodial activity of ethanolic leaves extract of traditional medicinal plant Xanthium strumarium in Plasmodium berghei-infected BALB/c mice along with phytochemical screening and acute toxicity test to support its traditional medicinal use as a malaria remedy. The ethanolic leaves extract of X. strumarium (ELEXS) 150, 250, 350 and 500 mg/kg/day demonstrated dose-dependent chemosuppression during early and established infection long with significant (p < 0.001) repository activity. The oral administration of 500 mg/kg/day concentration showed a maximum of 88.6% chemosuppression during early infection, which was more than that of the standard drug chloroquine (5 mg/kg/day) with 88.3% chemosuppression. However, 60% mortality has been found in this group. The LD(50) of ELEXS was found to be 1.5 g/kg/mouse. The administration of 350 mg/kg/day concentration of extract have been found to exert 90.40% chemosuppression during repository infection, which was well comparable to standard drug pyrimethamine (1.2 mg/kg/day) exerting 92.91% chemosuppression. The extract has been found to enhance mean survival time of mice from 21 to 26 days with 250 and 350 mg/kg/day concentrations, while 150 mg/kg/day concentration has been found to sustain all the mice up to 29 days which was similar to the employed standard drug chloroquine (5 mg/kg/day). All these findings support the ethanopharmacological use of X. strumarium as malarial remedy and indicate the potential of plant for active antiplasmodial components.

Antimalarial potential of homeopathic medicines against schizont maturation of Plasmodium berghei in short-term in vitro culture

In vitro assessment of antimalarial drug susceptibility of Plasmodium has been a major research success, which has paved the way for the understanding of parasite and rapid screening of antimalarial drugs for their effectiveness. In the present study a preliminary screening to check the antiplasmodial activity of mother tincture (ϕ) and various potencies (6C, 30C, 200C) of homeopathic medicines Cinchona officinalis/china (Chin.), Chelidonium majus (Chel.) and Arsenicum album (Ars.) were done by assessing the in vitro schizont maturation inhibition assay. A significant reduction in the growth of intraerythrocytic stages of P. berghei was observed with decreasing dilution of ϕ and various potencies of Chin., Chel. and Ars. exhibiting a dose dependent effect. Maximum schizont maturation inhibition was observed by Chin. ϕ (1:1), Chin. 30 (1:1, 1:2) and Chel. 30 (1:1) i.e. 80%. The standard drug CQ at 10 µM concentration exhibited 95.4±1.6% inhibition of schizont maturation. Ars. 30 (1:1) also have been found to possess strong antiplasmodial efficacy with 75.5±2.6% schizont inhibition. The presence of free merozoites in Ars. 200 with weak schizonticidal inhibition activity (40-45%) also pointed towards the ability of parasite to survive in the given drug pressure.

O estudo in vitro da susceptibilidade de Plasmodium a drogras antimaláricas representa um grande avanço nas pesquisas, abrindo novas rotas para o entendimento do parasite e da efetividade de drogas antiomaláricas. Nesse trabalho, realizamos um estudo preliminar da atividade antiplasmódica da tintura mãe (ϕ) e várias potências (6 cH, 30 cH, 200 cH) dos medicamentos homeopáticos China officinalis (Chin), Chelidonium majus (Chel) e Arsenicum album (Ars), através do estudo in vitro da inibição da maturação de esquizontes. Observamos uma redução significativa do crescimento do estágio intra-eritrócito do P. berghei conforme a tintura mãe e demais potências de Chin, Chel e Ars foram diluídas, observando-se um efeito dependente da dose. O máximo de inibição na maturação dos esquizontes (80%) foi observado com Chin ϕ (1:1), Chin 30 cH (1:1, 1:2) and Chel 30 cH (1:1). A droga Cloroquina (CQ), usada como controle, em uma concentração de 10µM, exibiu (95.4 ± 1.6) % de inibição. Ars 30cH (1:1) também apresentou uma forte eficácia antiplasmódica com (75.5 ± 2.6) % de inibição de esquizontes. A presence de merozoites livres com Ars 200 cH e uma fraca atividade inibidora (40-45%) indicam a habilidade do parasita em sobreviver na presença dessa droga.

Antimalarial potential of homeopathic medicines against schizont maturation of Plasmodium berghei in short-term in vitro culture

In vitro assessment of antimalarial drug susceptibility of Plasmodium has been a major research success, which has paved the way for the understanding of parasite and rapid screening of antimalarial drugs for their effectiveness. In the present study a preliminary screening to check the antiplasmodial activity of mother tincture (ϕ) and various potencies (6C, 30C, 200C) of homeopathic medicines Cinchona officinalis/china (Chin.), Chelidonium majus (Chel.) and Arsenicum album (Ars.) were done by assessing the in vitro schizont maturation inhibition assay. A significant reduction in the growth of intraerythrocytic stages of P. berghei was observed with decreasing dilution of ϕ and various potencies of Chin., Chel. and Ars. exhibiting a dose dependent effect. Maximum schizont maturation inhibition was observed by Chin. ϕ (1:1), Chin. 30 (1:1, 1:2) and Chel. 30 (1:1) i.e. 80%. The standard drug CQ at 10 µM concentration exhibited 95.4±1.6% inhibition of schizont maturation. Ars. 30 (1:1) also have been found to possess strong antiplasmodial efficacy with 75.5±2.6% schizont inhibition. The presence of free merozoites in Ars. 200 with weak schizonticidal inhibition activity (40-45%) also pointed towards the ability of parasite to survive in the given drug pressure.(AU)

O estudo in vitro da susceptibilidade de Plasmodium a drogras antimaláricas representa um grande avanço nas pesquisas, abrindo novas rotas para o entendimento do parasite e da efetividade de drogas antiomaláricas. Nesse trabalho, realizamos um estudo preliminar da atividade antiplasmódica da tintura mãe (ϕ) e várias potências (6 cH, 30 cH, 200 cH) dos medicamentos homeopáticos China officinalis (Chin), Chelidonium majus (Chel) e Arsenicum album (Ars), através do estudo in vitro da inibição da maturação de esquizontes. Observamos uma redução significativa do crescimento do estágio intra-eritrócito do P. berghei conforme a tintura mãe e demais potências de Chin, Chel e Ars foram diluídas, observando-se um efeito dependente da dose. O máximo de inibição na maturação dos esquizontes (80%) foi observado com Chin ϕ (1:1), Chin 30 cH (1:1, 1:2) and Chel 30 cH (1:1). A droga Cloroquina (CQ), usada como controle, em uma concentração de 10µM, exibiu (95.4 ± 1.6) % de inibição. Ars 30cH (1:1) também apresentou uma forte eficácia antiplasmódica com (75.5 ± 2.6) % de inibição de esquizontes. A presence de merozoites livres com Ars 200 cH e uma fraca atividade inibidora (40-45%) indicam a habilidade do parasita em sobreviver na presença dessa droga.(AU)

Screening of antiplasmodial efficacy of Ajuga bracteosa Wall ex. Benth.

The rising problem of Plasmodium resistance to the classical antimalarial drugs stresses the need to look for newer antiplasmodial components with effective and new mode of action. In the present study, the traditional medicinal plant Ajuga bracteosa has been screened for its antiplasmodial efficacy. The extract was found to possess significant in vitro antiplasmodial efficacy with an IC(50) of 10.0 µg/ml. Thus, the extract was further evaluated for its in vivo schizontocidal activity and efficacy in terms of survival time in Plasmodium berghei infected BALB/c mice. The extract at 250, 500, and 750 mg/kg/day exhibited significant (p<0.0001) blood schizontocidal activity during established infection with enhanced mean survival time comparable to that of standard drug chloroquine, 5 mg/kg/day. The significant schizontocidal activity and enhanced mean survival time of mice stress the need to identify and characterize active antiplasmodial principle from this plant.