curcumin and Malaria

Turmeric (Curcuma longa L.) is a popular spice containing curcumin that is responsible for its therapeutic effects. Curcumin with anti-inflammatory, antioxidant, anti-cancer, and antimicrobial activities has led to a lot of research focusing on it over the years. This systematic review aimed to evaluate research on the anti-Plasmodium berghei activity of curcumin and its derivatives.. Our study was performed according to PRISMA guidelines and was recorded in the database of a systematic review and preclinical meta-analysis of CAMARADESNC3Rs (SyRF). The search was performed in five databases, namely Scopus, PubMed, Web of Science, EMBASE, and Google Scholar, from 2010 to 2020. The following keywords were searched: "Plasmodium berghei", "Medicinal Plants", "Curcumin", "Concentration", Animals kind", "Treatment Durations", "Routes of Administration" and "in vivo".. Of the 3,500 papers initially obtained, 14 articles were reliable and were thus scrutinized. Animal models were included in all studies. The most commonly used animal strain was Albino (43%), followed by C57BL/6 (22%). The other studies used various murine strains, including BALB/c (14%) and ICR (7%). Two (14%) studies did not mention the strain of animal model used. Curcumin alone or in combination with other compounds depending on the dose used, route of administration, and animal model showed a moderate to strong anti-Plasmodium berghei effect.. According to the studies, curcumin has anti-malarial effects on Plasmodium berghei, and, however, its effect on human Plasmodium is unclear. Due to the side effects and drug resistance of current drugs in the treatment of human malaria, the use of new compounds with few or no side effects, such as curcumin, is recommended as an alternative or complementary treatment.

Topics: Animals; Anti-Inflammatory Agents; Antimalarials; Curcumin; Malaria; Mice; Plasmodium berghei

Malaria has been a major cause of morbidity and mortality in developing countries, particularly in Sub-Saharan Africa and South Asia. The global malaria situation is increasingly being challenging owing to lack of credible malaria vaccine and the emergence of drug resistance to most of the available antimalarials. They demand search for novel generation of drugs. Versatility and flexibility for structural modification of natural and synthetic analogues of curcumin and chalcone have been explored extensively for designing new antimalarial agent. Recent advances to our knowledge of parasite biology as well as the availability of the genome sequence, have opened up new vista in the firmament of antimalarial drug designing for identifying novel molecular targets. Curcumin and chalcones has been reported to exert anti-malarial effect by binding directly to numerous signaling molecules, such as histone acetyltransferase, histone deacetylase, sarco (endo) plasmic reticulum Ca(2+)-ATPase, cysteine proteases etc. This review highlights insights the more recent antimalarial activities of these compounds, their mechanisms of action, molecular targets and relevant structureactivity relationship studies. Natural lead compounds like chalcone and curcumin have shown good and optimal binding to many enzymes present in parasite and can be explored as molecular targets for in silico studies to develop new, affordable and effective antimalarial drugs. With no credible malaria vaccine in sight, there is an imperative need to develop new drugs with different mechanisms of action to help preclude issues of cross-resistance.

Topics: Antimalarials; Chalcone; Curcumin; Drug Resistance; Histone Acetyltransferases; Humans; Malaria; Plasmodium; Structure-Activity Relationship

Members of the Curcuma plant species (Zingiberaceae) have been used for centuries in cooking, cosmetics, staining and in traditional medicine as "omnipotent" remedies. Herbal preparations made with, and molecules extracted from, Curcuma have been shown to possess a wide variety of pharmacological properties against malignant proliferation, hormonal disorders, inflammation, and parasitosis among other conditions. This review evaluates Curcuma and its associated bioactive compounds, particularly focusing on studies examining the parasiticidal activity of these components against the tropical parasites Plasmodium, leishmania, Trypanosoma, Schistosoma and more generally against other cosmopolitan parasites (nematodes, Babesia, Candida, Giardia, Coccidia and Sarcoptes).

Topics: Animals; Antiparasitic Agents; Babesiosis; Coccidiosis; Curcuma; Curcumin; Giardiasis; Helminthiasis; Humans; Leishmaniasis; Malaria; Parasites; Parasitic Diseases; Plant Preparations; Scabies; Schistosomiasis; Trypanosomiasis

The clinical manifestations of cerebral malaria (CM) are well correlated with underlying major pathophysiological events occurring during an acute malaria infection, the most important of which, is the adherence of parasitized erythrocytes to endothelial cells ultimately leading to sequestration and obstruction of brain capillaries. The consequent reduction in blood flow, leads to cerebral hypoxia, localized inflammation and release of neurotoxic molecules and inflammatory cytokines by the endothelium. The pharmacological regulation of these immunopathological processes by immunomodulatory molecules may potentially benefit the management of this severe complication. Adjunctive therapy of CM patients with an appropriate immunomodulatory compound possessing even moderate anti-malarial activity with the capacity to down regulate excess production of proinflammatory cytokines and expression of adhesion molecules, could potentially reverse cytoadherence, improve survival and prevent neurological sequelae. Current major drug discovery programmes are mainly focused on novel parasite targets and mechanisms of action. However, the discovery of compounds targeting the host remains a largely unexplored but attractive area of drug discovery research for the treatment of CM. This review discusses the properties of the plant immune-modifier curcumin and its potential as an adjunctive therapy for the management of this complication.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antimalarials; Curcumin; Dietary Supplements; Drug Therapy, Combination; Humans; Immunologic Factors; Malaria; Malaria, Cerebral; Plants

Artemisinin, curcumin or quercetin, alone or in combination, were loaded in nutriosomes, special phospholipid vesicles enriched with Nutriose FM06®, a soluble dextrin with prebiotic activity, that makes these vesicles suitable for oral delivery. The resulting nutriosomes were sized between 93 and 146 nm, homogeneously dispersed, and had slightly negative zeta potential (around -8 mV). To improve their shelf life and storability over time, vesicle dispersions were freeze-dried and stored at 25 °C. Results confirmed that their main physico-chemical characteristics remained unchanged over a period of 12 months. Additionally, their size and polydispersity index did not undergo any significant variation after dilution with solutions at different pHs (1.2 and 7.0) and high ionic strength, mimicking the harsh conditions of the stomach and intestine. An in vitro study disclosed the delayed release of curcumin and quercetin from nutriosomes (∼53% at 48 h) while artemisinin was quickly released (∼100% at 48 h). Cytotoxicity assays using human colon adenocarcinoma cells (Caco-2) and human umbilical vein endothelial cells (HUVECs) proved the high biocompatibility of the prepared formulations. Finally, in vitro antimalarial activity tests, assessed against the 3D7 strain of Plasmodium falciparum, confirmed the effectiveness of nutriosomes in the delivery of curcumin and quercetin, which can be used as adjuvants in the antimalaria treatment. The efficacy of artemisinin was also confirmed but not improved. Overall results proved the possible use of these formulations as an accompanying treatment of malaria infections.

Topics: Adenocarcinoma; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Antimalarials; Artemisinins; Caco-2 Cells; Colonic Neoplasms; Curcumin; Endothelial Cells; Humans; Liposomes; Malaria; Quercetin

It has been shown that curcumin (Cur) has anti-plasmodial activity; however, its weak bioavailability, rapid metabolism, and limited chemical stability have restricted its application in clinical usages. Nanostructured lipid carriers (NLCs) are a type of Drug-Delivery Systems (DDSs) whose core matrix is composed of both solid and liquid lipids.. The aim of the current study was to prepare and characterize curcumin-loaded nanostructured lipid carriers (Cur-NLC) for malaria treatment.. For producing NLC, coconut oil and cetyl palmitate were selected as a liquid and solid lipid, respectively. In order to prepare the Cur-NLC, the microemulsion method was applied. General toxicity assay on Artemia salina as well as hemocompatibility was investigated. Anti-plasmodial activity was studied on mice infected with Plasmodium berghei.. The NLCs mean particle size and Polydispersity Index (PI) were 145 nm and 0.3, respectively. Further, the zeta potential of the Cur-NLC was -25 mV. The NLCs indicated a pseudo-spherical shape observed via transmission electron microscopy (TEM). The loading capacity and encapsulation efficacy of the obtained Cur-NLC were 3.1 ± 0.015% and 74 ± 3.32%, respectively. In vitro, Cur release profiles showed a sustained-release pattern up to 5 days in the synthesized Cur-NLC. The results of in vivo antiplasmodial activity against P. berghei revealed that antimalarial activity of Cur-NLC was significantly higher compared with that of free Cur at the dose of 40 mg/kg/day.. The results of this study suggested that NLC would be used as a potential nanocarrier for the treatment of malaria.

Topics: Animals; Antimalarials; Artemia; Curcumin; Disease Models, Animal; Drug Carriers; Drug Liberation; Female; Humans; Lipids; Malaria; Mice; Nanostructures; Particle Size; Plasmodium berghei; Surface Properties

In this paper, nutriosomes (phospholipid vesicles associated with Nutriose® FM06) were modified to obtain new systems aimed at enhancing the efficacy of curcumin in counteracting malaria infection upon oral administration. Eudragit® L100, a pH-sensitive co-polymer, was added to these vesicles, thus obtaining eudragit-nutriosomes, to improve their in vivo performances. Liposomes without eudragit and nutriose were also prepared as a reference. Cryo-TEM images showed the formation of multicompartment vesicles, with mean diameter around 300 nm and highly negative zeta potential. Vesicles were stable in fluids mimicking the gastro-intestinal content due to the high phospholipid concentration and the presence of gastro-resistant eudragit and digestion-resistant nutriose. Eudragit-nutriosomes disclosed promising performances in vitro and in vivo: they maximized the ability of curcumin to counteract oxidative stress in intestinal cells (Caco-2), which presumably reinforced its systemic efficacy. Orally-administered curcumin-loaded eudragit-nutriosomes increased significantly the survival of malaria-infected mice relative to free curcumin-treated controls.

Topics: Administration, Oral; Animals; Antimalarials; Antioxidants; Caco-2 Cells; Curcumin; Dextrins; Drug Carriers; Humans; Hydrogen-Ion Concentration; Liposomes; Malaria; Mice; Mice, Inbred BALB C; Nanoparticles; Oxidative Stress; Particle Size; Phospholipids; Polymers; Polymethacrylic Acids

Quinine, a treatment used in chloroquine-resistant falciparum malaria, was loaded into poly(ɛ-caprolactone) or Eudragit

Topics: Animals; Antimalarials; Caproates; Curcuma; Drug Carriers; Excipients; Lactones; Malaria; Mice; Nanocapsules; Particle Size; Plant Oils; Polymers; Polymethacrylic Acids; Quinine

Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (GSK3β)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3β. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development. At the highest dose tested (30 mg/kg body weight), both therapeutic and prophylactic administrations of curcumin resulted in suppression exceeding 50% and improved median survival time of infected mice compared to control. Western analysis revealed a 5.5-fold (therapeutic group) and 1.8-fold (prophylactic group) increase in phosphorylation of Ser 9 GSK3β and 1.6-fold (therapeutic group) and 1.7-fold (prophylactic group) increase in Ser 473 Akt in liver of curcumin-treated infected animals. Following P. berghei infection, levels of pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, and IL-4 were elevated by 7.5-, 35.0-, 33.0-, and 2.2-fold, respectively. Curcumin treatment (therapeutic) caused a significant decrease (by 6.0- and 2.0-fold, respectively) in serum TNF-α and IFN-γ level, while IL-10 and IL-4 were elevated (by 1.4- and 1.8-fold). Findings from the present study demonstrate for the first time that the antimalarial action of curcumin involved inhibition of GSK3β.

Topics: Animals; Antimalarials; Curcuma; Curcumin; Glycogen Synthase Kinase 3 beta; Humans; Interleukin-10; Interleukin-4; Malaria; Male; Mice; Mice, Inbred ICR; Plant Extracts; Plasmodium berghei; Tumor Necrosis Factor-alpha

Curcumin (Ccm) has shown immense potential as an antimalarial agent; however its low solubility and less bioavailability attenuate the in vivo efficacy of this potent compound. In order to increase Ccm's bioavailability, a number of organic/inorganic polymer based nanoparticles have been investigated. However, most of the present day nano based delivery systems pose a conundrum with respect to their complex synthesis procedures, poor in vivo stability and toxicity issues. Peptides due to their high biocompatibility could act as excellent materials for the synthesis of nanoparticulate drug delivery systems. Here, we have investigated dehydrophenylalanine (ΔPhe) di-peptide based self-assembled nanoparticles for the efficient delivery of Ccm as an antimalarial agent. The self-assembly and curcumin loading capacity of different ΔPhe dipeptides, phenylalanine-α,β-dehydrophenylalanine (FΔF), arginine-α,β-dehydrophenylalanine (RΔF), valine-α,β-dehydrophenylalanine (VΔF) and methonine-α,β-dehydrophenylalanine (MΔF) were investigated for achieving enhanced and effective delivery of the compound for potential anti-malarial therapy.. FΔF, RΔF, VΔF and MΔF peptides formed different types of nanoparticles like nanotubes and nanovesicles under similar assembling conditions. Out of these, F∆F nanotubes showed maximum curcumin loading capacity of almost 68 % W/W. Ccm loaded F∆F nanotubes (Ccm-F∆F) showed comparatively higher (IC50, 3.0 µM) inhibition of Plasmodium falciparum (Indo strain) as compared to free Ccm (IC50, 13 µM). Ccm-F∆F nano formulation further demonstrated higher inhibition of parasite growth in malaria infected mice as compared to free Ccm. The dipeptide nanoparticles were highly biocompatible and didn't show any toxic effect on mammalian cell lines and normal blood cells.. This work provides a proof of principle of using highly biocompatible short peptide based nanoparticles for entrapment and in vivo delivery of Ccm leading to an enhancement in its efficacy as an antimalarial agent.

Topics: Animals; Antimalarials; Biocompatible Materials; Cell Line; Chemistry, Pharmaceutical; Curcumin; Drug Delivery Systems; Drug Resistance; Malaria; Mice; Nanoparticles; Nanotubes, Peptide; Plasmodium falciparum

The present study was conducted to overcome the disadvantages associated with the poor water solubility and low bioavailability of curcumin by synthesizing nanotized curcumin and demonstrating its efficacy in treating malaria.. Nanotized curcumin was prepared by a modified emulsion-diffusion-evaporation method and was characterized by means of transmission electron microscopy, atomic force microscopy, dynamic light scattering, Zetasizer, Fourier transform infrared spectroscopy, and differential thermal analysis. The novelty of the prepared nanoformulation lies in the fact that it was devoid of any polymeric matrices used in conventional carriers. The antimalarial efficacy of the prepared nanotized curcumin was then checked both in vitro and in vivo.. The nanopreparation was found to be non-toxic and had a particle size distribution of 20-50 nm along with improved aqueous dispersibility and an entrapment efficiency of 45%. Nanotized curcumin (half maximal inhibitory concentration [IC50]: 0.5 μM) was also found to be ten-fold more effective for growth inhibition of Plasmodium falciparum in vitro as compared to its native counterpart (IC50: 5 μM). Oral bioavailability of nanotized curcumin was found to be superior to that of its native counterpart. Moreover, when Plasmodium berghei-infected mice were orally treated with nanotized curcumin, it prolonged their survival by more than 2 months with complete clearance of parasites in comparison to the untreated animals, which survived for 8 days only.. Nanotized curcumin holds a considerable promise in therapeutics as demonstrated here for treating malaria as a test system.

Topics: Animals; Antimalarials; Cell Line; Cell Survival; Curcumin; Humans; Kidney Function Tests; Liver Function Tests; Malaria; Mice; Nanoparticles; Particle Size; Plasmodium berghei; Plasmodium falciparum

The Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase (pfSAHH) enzyme has been considered as a potential chemotherapeutic target against malaria due to the amino acid differences found on binding sites of pfSAHH related to human SAHH. It has been reported that noraristeromycin and some curcumin derivatives have potential binding with the largest cavity of pfSAHH, which is also related to the binding with Nicotinamide-Adenine-Dinucleotide (NAD) and Adenosine (ADN). Our present work focuses on docking and ADMET studies to select potential inhibitors of pfSAHH. The binding of the selected inhibitor of the PfSAHH active site was analyzed using Molegro Virtual Docker. In this study, curcumin and its derivatives have been found to have higher binding affinity with pfSAHH than noraristeromycin. Seven amino acid residues Leu53, His54, Thr56, Lys230, Gly397, His398 and Phe407 of pfSAHH involved in binding with curcumin, are the same as those for noraristeromycin, which reveals that curcumin and noraristeromycin bind in the same region of pfSAHH. Curcumin has shown a strong interaction with hydrophobic amino acid residues of pfSAHH. Molecular Docking and ADMET predictions suggest that curcumin can be a potent inhibitor of pfSAHH with ability to modulate the target in comparatively smaller dose. Therefore, curcumin is likely to become a good lead molecule for the development of effective drug against malaria.

Topics: Adenosine; Adenosylhomocysteinase; Amino Acids; Animals; Binding Sites; Computer Simulation; Curcumin; Drug Discovery; Hydrophobic and Hydrophilic Interactions; Malaria; Models, Molecular; Molecular Structure; Plasmodium falciparum; Protein Binding; Protein Conformation

Curcumin (CC), a potential antimalarial drug, has poor water solubility, stability and oral bioavailability. To circumvent these pitfalls, lipid-based drug delivery systems (LBDDSs) with a high CC loading (30 mg/g) were formulated. In a biorelevant gastric medium, CC-LBDDSs formed particle sizes in the range of 30-40 nm. During in vitro lipolysis, 90-95% of the CC remained solubilized, whereas 5-10% of the CC precipitated as an amorphous solid, with a high rate of re-dissolution in a biorelevant intestinal medium. The transport of the CC-LBDDS across Caco-2 monolayers was enhanced compared with the transport of free drug because of the increased CC solubility. In Plasmodium berghei-infected mice, modest antimalarial efficacy was observed following oral treatment with CC-LBDDSs. However, the combination therapy of CC-LBDDS with a subtherapeutic dose of β-arteether-LBDDS provided an increase in protection and survival rate that was associated with a significant delay in recrudescence. These findings suggest that the combination of oral CC and β-arteether lipid-based formulations may constitute a promising approach for the treatment of malaria.

Topics: Animals; Antimalarials; Artemisinins; Caco-2 Cells; Curcumin; Drug Carriers; Drug Delivery Systems; Humans; Lipids; Malaria; Mice; Plasmodium berghei

The therapeutic efficacies of novel liposomal delivery systems based on artemisinin or artemisinin-based combination therapy with curcumin have been investigated and reported in this study. The developed liposomal formulations had proper characteristics as drug carriers for parental administration in terms of particle size, polydispersity, encapsulation efficacy and ζ-potential. Their physical and chemical stabilities were also evaluated. Furthermore, the in vivo antimalarial activity of artemisinin-based liposomal formulations was tested in Plasmodium berghei NK-65 infected mice, a suitable model for studying malaria because the infection presents structural, physiological and life cycle analogies with the human disease. Artemisinin, alone or in combination with curcumin, was encapsulated in conventional and PEGylated liposomes and its in vivo performance was assessed by comparison with the free drug. Mice were treated with artemisinin at the dosage of 50 mg/kg/days alone or plus curcumin as partner drug, administered at the dosage of 100 mg/kg/days. Artemisinin alone began to decrease parasitaemia levels only 7 days after the start of the treatment and it appeared to have a fluctuant trend in blood concentration which is reflected in the antimalarial effectiveness. By contrast, treatments with artemisinin-loaded conventional liposomes (A-CL), artemisinin-curcumin-loaded conventional liposomes (AC-CL), artemisinin-loaded PEGylated liposomes (A-PL), artemisinin-curcumin-loaded PEGylated liposomes (AC-PL) appeared to have an immediate antimalarial effect. Both nanoencapsulated artemisinin and artemisinin plus curcumin formulations cured all malaria-infected mice within the same post-inoculation period of time. Additionally, all formulations showed less variability in artemisinin plasma concentrations which suggested that A-CL, AC-CL, A-PL and AC-PL give a modified release of drug(s) and, as a consequence, a constant antimalarial effect during time. In particular, A-PL seems to give the most pronounced and statistically significant therapeutic effect in this murine model of malaria. The enhanced permanency in blood of A-PL suggests the use of these nanosystems as suitable passive targeted carriers for parasitic infections; this strong effect of formulation is added up to the mechanism of action of artemisinin which acts in the erythrocyte cycle stage of human host as a blood schizonticide.

Topics: Animals; Antimalarials; Artemisinins; Chemistry, Pharmaceutical; Curcumin; Drug Carriers; Drug Stability; Drug Therapy, Combination; Female; Liposomes; Malaria; Mice; Mice, Inbred BALB C; Nanoparticles; Particle Size; Plasmodium berghei; Polyethylene Glycols

Earlier studies in this laboratory have shown the potential of artemisinin-curcumin combination therapy in experimental malaria. In a parasite recrudescence model in mice infected with Plasmodium berghei (ANKA), a single dose of alpha,beta-arteether (ART) with three oral doses of curcumin prevented recrudescence, providing almost 95% protection. The parasites were completely cleared in blood with ART-alone (AE) or ART+curcumin (AC) treatments in the short-term, although the clearance was faster in the latter case involving increased ROS generation. But, parasites in liver and spleen were not cleared in AE or AC treatments, perhaps, serving as a reservoir for recrudescence. Parasitemia in blood reached up to 60% in AE-treated mice during the recrudescence phase, leading to death of animals. A transient increase of up to 2-3% parasitemia was observed in AC-treatment, leading to protection and reversal of splenomegaly. A striking increase in spleen mRNA levels for TLR2, IL-10 and IgG-subclass antibodies but a decrease in those for INFγ and IL-12 was observed in AC-treatment. There was a striking increase in IL-10 and IgG subclass antibody levels but a decrease in INFγ levels in sera leading to protection against recrudescence. AC-treatment failed to protect against recrudescence in TLR2(-/-) and IL-10(-/-) animals. IL-10 injection to AE-treated wild type mice and AC-treated TLR2(-/-) mice was able to prolong survival. Blood from the recrudescence phase in AE-treatment, but not from AC-treatment, was able to reinfect and kill naïve animals. Sera from the recrudescence phase of AC-treated animals reacted with several parasite proteins compared to that from AE-treated animals. It is proposed that activation of TLR2-mediated innate immune response leading to enhanced IL-10 production and generation of anti-parasite antibodies contribute to protective immunity in AC-treated mice. These results indicate a potential for curcumin-based combination therapy to be tested for prevention of recrudescence in falciparum and relapse in vivax malaria.

Topics: Animals; Antimalarials; Artemisinins; Curcumin; Drug Therapy, Combination; Immunomodulation; Interferon-gamma; Interleukin-10; Interleukin-12; Malaria; Mice; Mice, Mutant Strains; Plasmodium berghei; Spleen; Toll-Like Receptor 2

Curcuminoids are poorly water-soluble compounds with promising antimalarial activity. To overcome some of the drawbacks of curcuminoids, we explored the potential of liposomes for the intravenous delivery of curcuminoids in a model of mouse malaria. The curcuminoids-loaded liposomes were formulated from phosphatidylcholine (soy PC) by the thin-film hydration method. Antimalarial activity of curcuminoids-loaded liposomes alone and in combination with α/β arteether when administered intravenously, was evaluated in Plasmodium berghei infected mice. Animals treated with curcuminoids-loaded liposomes showed lower parasitemia and higher survival when compared to control group (no treatment). Importantly, the combination therapy of curcuminoids-loaded liposomes (40 mg/kg body wt) along with α/β arteether (30 mg/kg body wt) was able to not only cure infected mice but also prevented recrudescence. These data suggest that curcuminoids-loaded liposomes may show promise as a formulation for anti-malarial therapy.

Topics: Animals; Antimalarials; Artemisinins; Curcuma; Curcumin; Diarylheptanoids; Disease Models, Animal; Hemolysis; Humans; Liposomes; Malaria; Mice; Phytotherapy; Plant Extracts; Plant Roots; Plasmodium berghei; Polyphenols

In the present work, curcuminoids-loaded lipid nanoparticles for parenteral administration were successfully prepared by a nanoemulsion technique employing high-speed homogenizer and ultrasonic probe. For the production of nanoparticles, trimyristin, tristerin and glyceryl monostearate were selected as solid lipids and medium chain triglyceride (MCT) as liquid lipid. Scanning electron microscopy (SEM) revealed the spherical nature of the particles with sizes ranging between 120 and 250 nm measured by photon correlation spectroscopy (PCS). The zeta potential of the particles ranged between -28 and -45 mV depending on the nature of the lipid matrix produced, which also influenced the entrapment efficiency (EE) and drug loading capacity (LC) found to be in the range of 80-94% and 1.62-3.27%, respectively. The LC increased reciprocally on increasing the amount of MCT as confirmed by differential scanning calorimetry (DSC). DSC analyses revealed that increasing imperfections within the lipid matrix allowed for increasing encapsulation parameters. Nanoparticles were further sterilized by filtration process which was found to be superior over autoclaving in preventing thermal degradation of thermo-sensitive curcuminoids. The in vivo pharmacodynamic activity revealed 2-fold increase in antimalarial activity of curcuminoids entrapped in lipid nanoparticles when compared to free curcuminoids at the tested dosage level.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Calorimetry, Differential Scanning; Curcumin; Drug Compounding; Drug Stability; Glycerides; Hemolysis; Humans; Kinetics; Lipids; Malaria; Mice; Microscopy, Electron, Scanning; Nanoparticles; Particle Size; Plasmodium berghei; Solubility; Temperature; Triglycerides

Herbal extracts of Andrographis paniculata (AP) and Hedyotis corymbosa (HC) are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south Asian sub-continent. Methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (MRC-pf-20) and resistant (MRC-pf-303) strains of Plasmodium falciparum for their anti-malarial activity.. Growth inhibition was determined using different concentrations of these plant extracts on synchronized P. falciparum cultures at the ring stage. The interactions between these two plant extracts and individually with curcumin were studied in vitro. The performance of these two herbal extracts in isolation and combination were further evaluated in vivo on Balb/c mice infected with Plasmodium berghei ANKA and their efficacy was compared with that of curcumin. The in vivo toxicity of the plant derived compounds as well as their parasite stage-specificity was studied.. The 50% inhibitory concentration (IC50) of AP (7.2 microg/ml) was found better than HC (10.8 microg/ml). Combination of these two herbal drugs showed substantial enhancement in their anti-malarial activity. Combinatorial effect of each of these with curcumin also revealed anti-malarial effect. Additive interaction between the plant extracts (AP + HC) and their individual synergism with curcumin (AP+CUR, HC+CUR) were evident from this study. Increased in vivo potency was also observed with the combination of plant extracts over the individual extracts and curcumin. Both the plant extracts were found to inhibit the ring stage of the parasite and did not show any in vivo toxicity, whether used in isolation or in combination.. Both these two plant extracts in combination with curcumin could be an effective, alternative source of herbal anti-malarial drugs.

Topics: Andrographis; Animals; Antimalarials; Curcumin; Hedyotis; Malaria; Malaria, Falciparum; Mice; Mice, Inbred BALB C; Phytotherapy; Plant Extracts; Plant Leaves; Plant Stems; Plasmodium berghei; Plasmodium falciparum

Recent studies have proposed curcumin as a potential partner for artemisinin in artemisinin combination therapies to treat malaria infections. The efficacy of curcumin alone and in combination with artemisinin was evaluated on a clone of Plasmodium chabaudi selected for artemisinin resistance in vivo. The addition of piperine as an enhancer of curcumin activity was also tested. Results indicated that curcumin, both alone and in combination with piperine had only a modest antimalarial effect and was not able to reverse the artemisinin-resistant phenotype or significantly affect growth of the tested clone when used in combination with artemisinin. This is in contrast with previous in vivo work and calls for further experimental evaluation of the antimalarial potential of curcumin.

Topics: Administration, Oral; Alkaloids; Animals; Anti-Infective Agents; Artemisinins; Benzodioxoles; Biological Availability; Curcumin; Drug Resistance; Drug Therapy, Combination; Malaria; Male; Mice; Parasitemia; Piperidines; Plasmodium chabaudi; Polyunsaturated Alkamides

Artemisinin and curcumin show an additive interaction in killing Plasmodium falciparum in culture. In vivo, 3 oral doses of curcumin following a single injection of alpha,beta-arteether to Plasmodium berghei-infected mice are able to prevent recrudescence due to alpha,beta-arteether monotherapy and ensure almost 100% survival of the animals.

Topics: Animals; Antimalarials; Artemisinins; Curcumin; Drug Therapy, Combination; Inhibitory Concentration 50; Malaria; Mice; Parasitemia; Plasmodium berghei; Plasmodium falciparum; Sesquiterpenes; Survival Analysis; Treatment Outcome

Malaria remains a major global health concern. New, inexpensive, and effective antimalarial agents are urgently needed. Here we show that curcumin, a polyphenolic organic molecule derived from turmeric, inhibits chloroquine-resistant Plasmodium falciparum growth in culture in a dose dependent manner with an IC(50) of approximately 5 microM. Additionally, oral administration of curcumin to mice infected with malaria parasite (Plasmodium berghei) reduces blood parasitemia by 80-90% and enhances their survival significantly. Thus, curcumin may represent a novel treatment for malarial infection.

Topics: Animals; Antimalarials; Curcumin; Inhibitory Concentration 50; Malaria; Male; Mice; Parasitemia; Plasmodium berghei; Plasmodium falciparum; Survival Rate