Anti-Toxoplasma In Vitro and In Vivo Activity of Pyrus boissieriana Arbutin-Rich Fraction.

PURPOSE: Pyrus boissieriana is a rich source of arbutin and has been used in herbal medicine to treat infectious diseases. This study aimed to investigate the effect of the arbutin-rich fraction of Pyrus boissieriana aerial parts on Toxoplasma gondii In Vitro and In Vivo. METHODS: An arbutin-rich fraction of P. boissieriana was prepared beforehand. Flow cytometry was used to evaluate the effect of different concentrations (1-512 µg/ml) of the P. boissieriana arbutin-rich fraction on Toxoplasma tachyzoites (RH strain). The cytotoxicity of the concentrations on the macrophage J774 cell line was also investigated by MTT assay. For In Vivo investigation, 4-6-week-old female mice infected with the RH strain of T. gondii were treated with different doses (16, 32, 64, 256, and 512 mg/kg) of the fraction using gavage. RESULTS: The highest and lowest lethality of the tachyzoites were 89.6% and 25.9% related to the concentrations of 512 µg/ml and 1 µg/ml, respectively, with an IC50 value of 18.1 µg/ml ± 0.37. The cytotoxicity test showed an IC50 value of 984.3 µg/ml ± 0.76 after 48 h incubation. The mean survival of mice at the lowest treated dose (16 mg/kg) was 6.6 days, and it was 15 days at the highest dose (512 mg/kg). The concentrations of 512, 256, 128, and 64 mg/kg of the fraction compared to the negative control (6.2 days mean survival) significantly increased the survival time of mice (P < 0.001, P = 0.009, P = 0.018, and P = 0.021, respectively). CONCLUSION: The results showed that the arbutin-rich fraction of P. boissieriana is effective against T. gondii In Vitro and In Vivo and may be a reliable alternative to conventional treatment for toxoplasmosis, although further studies are necessary.

In vitro anti-Toxoplasma gondii activity of Ganoderma lucidum extracts.

OBJECTIVE: Ganoderma extracts have the potential to be used as anti-cancer, anti-inflammatory, immunomodulator, and antimicrobial agents, as evaluated in numerous studies. This study was aimed to determine the lethal and inhibitory effects of aqueous, hydroalcoholic, and alcoholic extracts of Ganoderma lucidum on Toxoplasma gondii RH strain tachyzoites, in vitro. RESULTS: All three types of extracts showed toxoplasmacidal effects. The highest percentage of mortality was related to hydroalcoholic extract. The EC50 of Ganoderma extracts for tachyzoites were 76.32, 3.274, and 40.18 for aqueous, hydroalcoholic and alcoholic extracts, respectively. The selectivity index obtained for hydroalcoholic extract was 71.22, showing the highest activity compared to other extracts. According to our findings, the hydroalcoholic part was the most effective substance among the extracts. This basic study showed obvious anti-toxoplasma effect of Ganoderma lucidum extracts. These extracts can be used as candidates for further in-depth and comprehensive studies especially In vivo experiments to prevent toxoplasmosis.

Pantothenate biosynthesis in Toxoplasma gondii tachyzoites is not a drug target.

Toxoplasma gondii is a pervasive apicomplexan parasite that can cause severe disease and death in immunocompromised individuals and the developing foetus. The treatment of toxoplasmosis often leads to serious side effects and novel drugs and drug targets are therefore actively sought. In 2014, Mageed and colleagues suggested that the T. gondii pantothenate synthetase, the enzyme responsible for the synthesis of the vitamin B5 (pantothenate), the precursor of the important cofactor, coenzyme A, is a good drug target. Their conclusion was based on the ability of potent inhibitors of the M. tuberculosis pantothenate synthetase to inhibit the proliferation of T. gondii tachyzoites. They also reported that the inhibitory effect of the compounds could be antagonised by supplementing the medium with pantothenate, supporting their conclusion that the compounds were acting on the intended target. Contrary to these observations, we find that compound SW314, one of the compounds used in the Mageed et al. study and previously shown to be active against M. tuberculosis pantothenate synthetase in vitro, is inactive against the T. gondii pantothenate synthetase and does not inhibit tachyzoite proliferation, despite gaining access into the parasite in situ. Furthermore, we validate the recent observation that the pantothenate synthetase gene in T. gondii can be disrupted without detrimental effect to the survival of the tachyzoite-stage parasite in the presence or absence of extracellular pantothenate. We conclude that the T. gondii pantothenate synthetase is not essential during the tachyzoite stage of the parasite and it is therefore not a target for drug discovery against T. gondii tachyzoites.

Biogenic selenium nanoparticles: trace element with promising anti-toxoplasma effect.

Toxoplasmosis is an opportunistic infection caused by the coccidian Toxoplasma gondii which represents a food and water contaminant. The available chemotherapeutic agents for toxoplasmosis are limited and the choice is difficult when considering the side effects. Selenium is an essential trace element. It is naturally found in dietary sources, especially seafood, and cereals. Selenium and selenocompounds showed anti-parasitic effects through antioxidant, immunomodulatory, and anti-inflammatory mechanisms. The present study evaluated the potential efficacy of environmentally benign selenium nanoparticles (SeNPs) against acute toxoplasmosis in a mouse model. SeNPs were fabricated by nanobiofactory Streptomyces fulvissimus and characterized by different analytical techniques including, UV-spectrophotometry, transmission electron microscopy, EDX, and XRD. Swiss albino mice were infected with Toxoplasma RH strain in a dose of 3500 tachyzoites in 100 µl saline to induce acute toxoplasmosis. Mice were divided into five groups. Group I: non-infected, non-treated, group II: infected, non-treated, group III: non-infected, treated with SeNPs, group IV: infected, treated with co-trimoxazole (sulfamethoxazole/trimethoprim) and group V: infected, treated with SeNPs. There was a significant increase in survival time in the SeNPs-treated group and minimum parasite count was observed compared to untreated mice in hepatic and splenic impression smears. Scanning electron microscopy showed tachyzoites deformity with multiple depressions and protrusions, while transmission electron microscopy showed excessive vacuolization and lysis of the cytoplasm, especially in the area around the nucleus and the apical complex, together with irregular cell boundary and poorly demarcated cell organelles. The present study demonstrated that the biologically synthesized SeNPs can be a potential natural anti-Toxoplasma agent in vivo.

The Heptaprenyl Diphosphate Synthase (Coq1) Is the Target of a Lipophilic Bisphosphonate That Protects Mice against Toxoplasma gondii Infection.

Prenyldiphosphate synthases catalyze the reaction of allylic diphosphates with one or more isopentenyl diphosphate molecules to form compounds such as farnesyl diphosphate, used in, e.g., sterol biosynthesis and protein prenylation, as well as longer "polyprenyl" diphosphates, used in ubiquinone and menaquinone biosynthesis. Quinones play an essential role in electron transport and are associated with the inner mitochondrial membrane due to the presence of the polyprenyl group. In this work, we investigated the synthesis of the polyprenyl diphosphate that alkylates the ubiquinone ring precursor in Toxoplasma gondii, an opportunistic pathogen that causes serious disease in immunocompromised patients and the unborn fetus. The enzyme that catalyzes this early step of the ubiquinone synthesis is Coq1 (TgCoq1), and we show that it produces the C35 species heptaprenyl diphosphate. TgCoq1 localizes to the mitochondrion and is essential for in vitro T. gondii growth. We demonstrate that the growth defect of a T. gondii TgCoq1 mutant is rescued by complementation with a homologous TgCoq1 gene or with a (C45) solanesyl diphosphate synthase from Trypanosoma cruzi (TcSPPS). We find that a lipophilic bisphosphonate (BPH-1218) inhibits T. gondii growth at low-nanomolar concentrations, while overexpression of the TgCoq1 enzyme dramatically reduced growth inhibition by the bisphosphonate. Both the severe growth defect of the mutant and the inhibition by BPH-1218 were rescued by supplementation with a long-chain (C30) ubiquinone (UQ6). Importantly, BPH-1218 also protected mice against a lethal T. gondii infection. TgCoq1 thus represents a potential drug target that could be exploited for improved chemotherapy of toxoplasmosis. IMPORTANCE Millions of people are infected with Toxoplasma gondii, and the available treatment for toxoplasmosis is not ideal. Most of the drugs currently used are only effective for the acute infection, and treatment can trigger serious side effects requiring changes in the therapeutic approach. There is, therefore, a compelling need for safe and effective treatments for toxoplasmosis. In this work, we characterize an enzyme of the mitochondrion of T. gondii that can be inhibited by an isoprenoid pathway inhibitor. We present evidence that demonstrates that inhibition of the enzyme is linked to parasite death. In addition, the inhibitor can protect mice against a lethal dose of T. gondii. Our results thus reveal a promising chemotherapeutic target for the development of new medicines for toxoplasmosis.

Therapeutic potential of royal jelly to control Toxoplasma gondii infection in mice.

At present, there are several synthetic medications for toxoplasmosis therapy; however, these agents cannot be permanently applied because of adverse side effects or therapeutic failures and drug resistance in parasites. The present experimental investigation was aimed to study the effects of royal jelly (RJ) obtained from Apis mellifera in comparison with atovaquone against Toxoplasma gondii infection in mice. After treatment of infected mice with RJ at the doses of 200, 400, and 600 mg/kg for 14 consecutive days, we evaluated the therapeutic activity of RJ by measuring the mean number and the mean size of T. gondii tissue cysts, oxidant-antioxidant enzymes, pro-inflammatory cytokines, the mRNA expression levels of bradyzoite surface antigen 1 (BAG1), as well as the toxic effect on liver and kidney function. Treatment of the infected mice with RJ significantly (p < 0.001) decreased the mean number and the mean diameter of T. gondii tissue cysts and downregulated BAG1 in a dose-dependent response. After treatment of infected mice with RJ, the level of oxidative stress markers was significantly diminished, but a significant increase (p < 0.05) in the level of antioxidant markers such as glutathione peroxidase (GPx) and superoxide dismutase (SOD) enzymes was observed. Treatment of the infected mice with RJ significantly enhanced the level of pro-inflammatory cytokines IFN-γ and IL-1ß, whereas it caused no substantial change in the serum levels of liver and kidney enzymes. The findings of this in vivo study revealed the favorable therapeutic effect of RJ on latent T. gondii infection in mice. It was found that RJ considerably inhibited the infection by decreasing the number and size of tissue cysts, reducing oxidative stress, and boosting the level of pro-inflammatory cytokines, but had no significant toxic impact on the function of vital organs such as liver and kidney. However, additional surveys are required to confirm these findings and clarify the exact mechanisms and their efficiency in clinical subjects.

Therapeutic Potential and Safety of the Cinnamomum zeylanicum Methanolic Extract Against Chronic Toxoplasma gondii Infection in Mice.

Background: This experimental study determined the in vitro, in vivo, and toxicity effects of Cinnamomum zeylanicum methanolic extract (CZME) against Toxoplasma gondii infection. Methods: The in vitro activity of CZME T. gondii tachyzoites was studied by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Infected mice were treated with CZME for two weeks at doses of 20, 40, and 60 mg/kg/day. Then, the therapeutic effects of CZME were evaluated by assessing the mean number and mean size of T. gondii tissue cysts, oxidant-antioxidant enzymes, pro-inflammatory cytokines, and mRNA expression levels of bradyzoite surface antigen 1 (BAG1) by real-time PCR. Results: CZME significantly (p <0.001) increased the mortality rate of parasites in a dose- and time-dependent response. The mean number of intracellular tachyzoites was significantly reduced after CZME therapy. The treatment of infected mice with CZME resulted in a significant (p <0.001) downregulation of BAG1 and the level of lipid peroxidation (LPO) and nitric oxide (NO) as oxidative stress markers. However, a considerable rise (p <0.05) was found in the levels of antioxidant markers such as glutathione peroxidase (GPx), catalase enzyme (CAT), and superoxide dismutase enzyme activity (SOD). In a dose-dependent response, after treatment of infected mice with CZME, the level of pro-inflammatory cytokines of IFN-γ, IL-1ß, and IL-12 was considerably elevated. CZME had no significant cytotoxicity on Vero cells, with a 50% cytotoxic concentration of 169.5 ± 5.66 µg/ml. Conclusion: The findings confirmed the promising therapeutic effects of CZME on chronic toxoplasmosis in mice. Nevertheless, further investigations must confirm these results, elucidate its precise mechanisms, and examine its effectiveness in human volunteers.

In Vitro and In Vivo Anti-Toxoplasma Activities of Dracocephalum kotschyi Extract in Experimental Models of Acute Toxoplasmosis.

BACKGROUND: The problem of resistance to antiparasitic drugs, associated with their side effects, suggest exploring other alternatives, including medicinal plants. Dracocephalum kotschyi (D. kotschyi), for example, from Lamiaceae family, is a plant widely used in Iran and in many countries, and to which interesting pharmacological properties have been attributed. This study aimed to investigate in vitro and in vivo anti-Toxoplasma activities of D. kotschyi extract in experimental models of acute toxoplasmosis. METHODS: Anti-Toxoplasma activity of the extracts in vitro was performed on Vero Cell, using the MTT test. Vero cell were infected with (3 × 105 tachyzoites/well) following treatment with Dichloromethane (F1), dichloromethane: methanol (F2), methanol (F3), methanol: water (F4), and deionized water (F5) extracts of D. kotschyi, and pyrimethamine and sulfadiazine (positive control). MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was used to measure cell viability. Effects of extracts on tachyzoites viability were evaluated by trypan blue exclusion method, followed by light microscopy. For in vivo test, 18 groups of 8-10-week-old Inbred Balb/c mice weighing 18-20 g, were intraperitoneally infected with 2 × 103 tachyzoites and then treated with sterile PBS (negative control), pyrimethamine (25 mg/kg) and sulfadiazine (500 mg/kg) as positive controls, and F1 to F5 extracts (at doses 50, 100 and 200 mg/kg). RESULTS: The 50% Inhibitory Concentration of F1 extract, F2 extract, Sulfadiazine (Positive control) and Pyrimethamine (Positive control) were 8.77 µg, 7.1 µg 391.18 µg, and 84.20 µg, respectively, while the selectivity indices were 15.667, 30.197, 1.552 and 4.064, respectively. In vivo anti-Toxoplasma activity test showed that Methanol: water (F-4) 50 extract was more active than the positive control. CONCLUSIONS: Indeed, the extract allowed a survival rate of 10% of the mice, compared to 0% for all the other groups. D. kotschyi has the potential to be valorized in the management of toxoplasmosis.

Evaluation of Origanum vulgare Essential Oil and Its Active Ingredients as Potential Drugs for the Treatment of Toxoplasmosis.

Toxoplasma gondii is a serious hazard to public health and animal husbandry. Due to the current dilemma of treatment of toxoplasmosis, it is urgent to find new anti-T. gondii drugs to treat toxoplasmosis. In this study, the anti-T. gondii activity of Origanum vulgare essential oil (Ov EO) was firstly studied, and then, carvanol (Ca), the main ingredient of Ov EO was evaluated using the MTT assay on human foreskin fibroblast (HFF) cells in vitro. The cytotoxicity was evaluated using the MTT assay on HFF cells. The CC50 of Ov EO and Ca was 134.9 and 43.93 µg/ml, respectively. Both of them exhibited anti-parasitic activity, and inhibited the growth of T. gondii in a dose-dependent manner. For the inhibition effect, Ca was better than Ov EO at the same concentration, the IC50 of Ov EO and Ca was 16.08 and 7.688 µg/ml, respectively. In addition, treatment with Ca, was found to change the morphology of T. gondii tachyzoites and made their shapes curl up. These results showed that Ca was able to inhibit the proliferation of T. gondii by reducing invasion, which may be due to its detrimental effect on the mobility of tachyzoites. Our results indicated that Ca could be a potential new and effective drug for treating toxoplasmosis.

Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities.

Toxoplasma gondii is an apicomplexan parasite causing toxoplasmosis, a common disease, which is most typically asymptomatic. However, toxoplasmosis can be severe and even fatal in immunocompromised patients and fetuses. Available treatment options are limited, so there is a strong impetus to develop novel therapeutics. This review focuses on the role of oxidative stress in the pathophysiology and treatment of T. gondii infection. Chemical compounds that modify redox status can reduce the parasite viability and thus be potential anti-Toxoplasma drugs. On the other hand, oxidative stress caused by the activation of the inflammatory response may have some deleterious consequences in host cells. In this respect, the potential use of natural antioxidants is worth considering, including melatonin and some vitamins, as possible novel anti-Toxoplasma therapeutics. Results of in vitro and animal studies are promising. However, supplementation with some antioxidants was found to promote the increase in parasitemia, and the disease was then characterized by a milder course. Undoubtedly, research in this area may have a significant impact on the future prospects of toxoplasmosis therapy.

The delayed death-causing nature of Rosmarinus officinalis leaf extracts and their mixture within experimental chronic toxoplasmosis: Therapeutic and prophylactic implications.

BACKGROUND: The restricted effect, significant toxicity, and emerging resistance of anti-toxoplasmosis synthetic agents impose the search for alternatives. The current research aimed to evaluate the prophylactic and therapeutic efficacy of Rosmarinus officinalis extracts and their mixtures against chronic murine toxoplasmosis and to clarify the phenomenon of delayed death. METHODS: This research included two experimental designs, the first to test the preventive and curative efficacy of the extracts and the second to assess delayed death in mice infected with the ME49 strain of Toxoplasma gondii. The essential oils of the plant were analyzed by gas chromatography/mass spectrometry. RESULTS: Treatment with a mixture of rosemary extracts displayed reduction rates of 81% for T. gondii cyst burden and 23% for cyst viability. The reinfected group with the pretreated cysts reported 93.4% reduction in cyst burden and 95.4% in cyst viability. Moreover, 90% reduction of the infectivity rate was obtained. The therapeutic efficacy of this mixture was superior to its valuable prophylactic effect. Histopathological examination of liver and brain tissue exhibited marked improvement. Both extracts possess free radical scavenging and antioxidant activities evidenced by high expression of iNOS stain. Our results were signified by low BAG-1 gene expression and massive mutilation of T. gondii cyst in the targeted group using scanning electron microscopy. Analysis of R. officinalis revealed the presence of isobornylformate as a novel ingredient. CONCLUSIONS: R. officinalis displays a therapeutic rather than prophylactic potential, indicating the emergence of an effective safe alternative therapy.

Myrtus communis Essential Oil; Anti-Parasitic Effects and Induction of the Innate Immune System in Mice with Toxoplasma gondii Infection.

BACKGROUND: Myrtus communis (M. communis) is a wild aromatic plant used for traditional herbal medicine that can be demonstrated in insecticidal, antioxidant, anti-inflammatory, and antimicrobial activity of its essential oils (MCEO). AIM: The present study aimed to evaluate the prophylactic effects of M. communis essential oil (MCEO) against chronic toxoplasmosis induced by the Tehran strain of Toxoplasma gondii in mice. METHODS: Gas chromatography/mass spectrometry (GC/MS) analysis was performed to determine the chemical composition of MCEO. Mice were then orally administrated with MCEO at the doses of 100, 200, and 300 mg/kg/day and also atovaquone 100 mg/kg for 21 days. On the 15th day, the mice were infected with the intraperitoneal inoculation of 20-25 tissue cysts from the Tehran strain of T. gondii. The mean numbers of brain tissue cysts and the mRNA levels of IL-12 and IFN-γ in mice of each tested group were measured. RESULTS: By GC/MS, the major constituents were α-pinene (24.7%), 1,8-cineole (19.6%), and linalool (12.6%), respectively. The results demonstrated that the mean number of T. gondii tissue cysts in experimental groups Ex1 (p < 0.05), Ex2 (p < 0.001) and Ex3 (p < 0.001) was meaningfully reduced in a dose-dependent manner compared with the control group (C2). The mean diameter of tissue cyst was significantly reduced in mice of the experimental groups Ex2 (p < 0.01) and Ex3 (p < 0.001). The results demonstrated that although the mRNA levels of IFN-γ and IL-12 were elevated in all mice of experimental groups, a significant increase (p < 0.001) was observed in tested groups of Ex2 and Ex3 when compared with control groups. CONCLUSION: The findings of the present study demonstrated the potent prophylactic effects of MCEO especially in the doses 200 and 300 mg/kg in mice infected with T. gondii. Although the exceptional anti-Toxoplasma effects of MCEO and other possessions, such as improved innate immunity and low toxicity are positive topics, there is, however, a need for more proof from investigations in this field.

Curcumin@metal organic frameworks nano-composite for treatment of chronic toxoplasmosis.

Toxoplasmosis is a zoonotic protozoal disease caused by Toxoplasma gondii, an intracellular opportunistic protozoan parasite that can infect any warm-blooded vertebrate cell. In this study, zirconium, and iron-based metal-organic framework was prepared according to the solvothermal method. New nanocomposite (Curcumin@MOFs) was prepared by reacting curcumin with amino-functionalized metal-organic frameworks (Fe-MOF and UiO-66-NH2). Besides characterizations of the composite by powder X-ray diffraction and scanning electron microscope, nano-Curcumin@MOFs was used as a new novel structure as atrial for treatment of chronic toxoplasmosis. Results showed a reduced number of brain cysts, high levels of serum Toxo IgG, and normal histo-morphology with preserved parenchymal, and stromal tissues in rats groups treated with curcumin and Curcumin@MOFs nanocomposite.

Copaifera spp. oleoresins impair Toxoplasma gondii infection in both human trophoblastic cells and human placental explants.

The combination of pyrimethamine and sulfadiazine is the standard care in cases of congenital toxoplasmosis. However, therapy with these drugs is associated with severe and sometimes life-threatening side effects. The investigation of phytotherapeutic alternatives to treat parasitic diseases without acute toxicity is essential for the advancement of current therapeutic practices. The present study investigates the antiparasitic effects of oleoresins from different species of Copaifera genus against T. gondii. Oleoresins from C. reticulata, C. duckei, C. paupera, and C. pubiflora were used to treat human trophoblastic cells (BeWo cells) and human villous explants infected with T. gondii. Our results demonstrated that oleoresins were able to reduce T. gondii intracellular proliferation, adhesion, and invasion. We observed an irreversible concentration-dependent antiparasitic action in infected BeWo cells, as well as parasite cell cycle arrest in the S/M phase. The oleoresins altered the host cell environment by modulation of ROS, IL-6, and MIF production in BeWo cells. Also, Copaifera oleoresins reduced parasite replication and TNF-α release in villous explants. Anti-T. gondii effects triggered by the oleoresins are associated with immunomodulation of the host cells, as well as, direct action on parasites.

Treatment with Lycopodium clavatum 200dH Intensifies Kidney and Liver Injury in Mice Infected with Toxoplasma gondii.

The effects of infection with Toxoplasma gondii vary from asymptomatic to the development of alterations in various organs (including the liver and kidneys) which may be irreversible, and lead to the death of the host. Whereas homeopathy is an alternative and effective method for treating various diseases, including those caused by protozoa, we questioned the effect of using Lycopodium clavatum in mice infected with T. gondii. One hundred male Swiss mice, 60 days old, were divided into four groups (n = 25/group): NIC (uninfected and untreated control), IC (infected and treated with un-dynamized 7% alcohol solution [vehicle]), G48 (infected and treated 48 h before infection and treated three more times; at 2, 4, and 6 days post-infection (dpi) with L. clavatum 200dH), and G72 (infected and treated for 3 consecutive days before infection with L. clavatum 200dH). In this study, physiological, histopathological, and immunological parameters were evaluated. The L. clavatum 200dH intensified renal damage in mice infected with T. gondii from 7 dpi, causing severe and progressive alterations during this period, such as various degrees of inflammation, edema, atrophy, and tubular cystic dilation, degenerated tubules with intra-cytoplasmic vacuoles and coalescing spots, severe vascular lesions, glomerulonephritis, and peri-glomerular congestion. In the G72 animals, which received L. clavatum 200dH, more severe cortex damage was observed (91.66-96.66%) as compared to the IC group (55-80%) and more renal corpuscle, and renal tubule injury was observed (80 ± 5 to 96.7% ± 2.89 of the total area) during all periods, as compared to the IC group (p < 0.05). Both groups presented high liver enzyme levels, and the highest values for AST were observable at 60 dpi. We observed significant increases of type I and III collagen, as well as high levels of TGF-ß1 in both organs of the treated animals, the main factor involved in fibrosis in areas damaged by the process. L. clavatum 200dH intensifies kidney and liver alterations in mice infected with T. gondii. Our results reinforce caution when indicating administration schemes and dosages for ultra-diluted drugs.

Screening of a library of traditional Chinese medicines to identify compounds and extracts which inhibit Toxoplasma gondii growth.

Toxoplasma gondii can cause severe encephalitis in immunocompromised patients. Although pyrimethamine and sulphadiazine have been standard therapeutic agents for the treatment of acute toxoplasmosis, they have toxic side effects. Therefore, there is a need to identify new drugs that are less toxic. Some traditional Chinese medicines (TCMs) have shown good efficacy in controlling T. gondii replication in mouse models. Here, we screened a natural product library comprising TCMs with the aim of identifying compounds and extracts with anti-toxoplasmosis activities. We found several hit compounds and extracts that could be candidates for new drugs against T. gondii infection.

Phytochemicals and Potential Therapeutic Targets on Toxoplasma gondii Parasite.

Identification of drug target in protozoan T. gondii is an important step in the development of chemotherapeutic agents. Likewise, exploring phytochemical compounds effective against the parasite can lead to the development of new drug agent that can be useful for prophylaxis and treatment of toxoplasmosis. In this review, we searched for the relevant literature on the herbs that were tested against T. gondii either in vitro or in vivo, as well as different phytochemicals and their potential activities on T. gondii. Potential activities of major phytochemicals, such as alkaloid, flavonoid, terpenoids and tannins on various target sites on T. gondii as well as other related parasites was discussed. It is believed that the phytochemicals from natural sources are potential drug candidates for the treatment of toxoplasmosis with little or no toxicity to humans.

Biogenic selenium nanoparticles target chronic toxoplasmosis with minimal cytotoxicity in a mouse model.

Introduction. Nanoparticles (NPs) have numerous biological benefits due to their large surface-volume ratio and convenient entry into cells compared to other particles. Previous research has shown the antimicrobial properties of biogenic selenium NPs (SeNps) and their effects on cellular immunomodulatory cytokines that play a key role in controlling infections.Aim. This study aimed to evaluate the therapeutic effects of SeNPs against chronic toxoplasmosis in mice.Methodology. Infected mice with Toxoplasma gondii (Tehran strain) were orally treated with SeNPs at doses of 2.5, 5 and 10 mg kg-1 once a day for 14 days. On the fifthteenth day, the mean number of brain-tissue cysts and the mRNA levels of TNF-α, IL-12, IL-10, IFN-γ and inducible nitric oxide synthase (iNOS) in the mice of each group were recorded. Moreover, serum clinical chemistry factors in the treated mice were examined to determine the safety of SeNPs.Results. The mean number of tissue cysts was significantly (P<0.001) decreased in mice treated with SeNPs in a dose-dependent manner compared with the control group. The mRNA levels of inflammatory cytokines were significantly increased in mice treated with SeNPs at a dose of 10 mg kg-1 compared with the control subgroup (P<0.05). No significant variation (P>0.05) observed in clinical chemistry parameters among the mice in the control subgroup compared with those treated with SeNPs.Conclusion. The findings demonstrated the therapeutic effects of SeNPs with no considerable toxicity against latent toxoplasmosis in the mouse model. Nevertheless, further studies are obligatory to reveal the exact anti-Toxoplasma mechanisms of SeNPs.

Anti-Toxoplasma activity of Sorghum bicolor-derived lipophilic fractions.

OBJECTIVE: Toxoplasma gondii, an intracellular zoonotic parasite, infects approximately a third of the world population. Current drugs for treatment of T. gondii infection have been challenged with ineffectiveness and adverse side effects. This necessitates development of new anti-Toxoplasma drugs. Sorghum bicolor [Moench] leaf extract has been used in African traditional medicine for the management of anemia and treatment of infectious diseases. We tested the in vitro anti-Toxoplasma inhibitory activity of S. bicolor's oil-like crude extracts and fractions against T. gondii and determined their cytotoxic effects on human host cells. RESULTS: Significant inhibitory activities against the growth of T. gondii tachyzoites were observed for the crude extract (IC50 = 3.65 µg/mL), the hexane-methanol fraction (IC50 = 2.74 µg/mL), and the hexane fraction (IC50 = 3.55 µg/mL) after 48 h of culture. The minimum cytotoxicity concentrations against HFF were 34.41, 16.92 and 7.23 µg/mL for crude extract, hexane-methanol and hexane fractions, respectively. The crude extract and fractions showed high antiparasitic effects with low cytotoxic effects. Further studies to determine synergistic activities and modes of action would provide impetus for the development of new toxoplasmosis drugs or nutraceuticals.

Synthesis and Biological Evaluation of (+)-Usnic Acid Derivatives as Potential Anti-Toxoplasma gondii Agents.

Six series of (+)-usnic acid derivatives were synthesized. The IC50 values of these compounds were determined in T. gondii infected HeLa cells (µM) and in HeLa cells (µM), and their selectivity indexes (SI) were calculated. In vitro, most of the derivatives tested in this study exhibited more anti activity than that of the parent compound (+)-usnic acid and the positive control drugs. Among these derivatives, methyl (E)-(1-(6-acetyl-7,9-dihydroxy-8,9b-dimethyl-1,3-dioxo-3,9b-dihydrodibenzo[b,d]furan-2(1H)-ylidene)ethyl)phenylalaninate (D3) showed the most effective anti-T. gondii activity (selectivity >2.77). In comparison with the clinically used positive control drugs sulfadiazine (selectivity 1.15), pyrimethamine (selectivity 0.89), spiramycin (selectivity 0.72), and the lead compound (+)-usnic acid (selectivity 0.96), D3 showed better results in vitro. Furthermore, D3 and (E)-6-acetyl-7,9-dihydroxy-8,9b-dimethyl-2-(1-(quinolin-6-ylamino)ethylidene)dibenzo[b,d]furan-1,3(2H,9bH)-dione (F3) had greater inhibitory effects on T. gondii (inhibition rates 76.0% and 64.6%) in vivo in comparison to spiramycin (inhibition rate 55.2%); in the peritoneal cavity of mice, the number of tachyzoites was significantly reduced (p < 0.001) in vivo. Additionally, some biochemical parameters were measured and spleen indexes were comprehensively evaluated, and the results indicated that mice treated with both compound D3 and compound F3 showed reduced hepatotoxicity and significantly enhanced antioxidative effects in comparison to the normal group. Granuloma and cyst formation were effected by the inhibition of compound D3 and compound F3 in liver sections. Overall, these results indicated that D3 and F3 for use as anti-T. gondii agents are promising lead compounds.