Inhibition of Toxoplasma gondii Growth by Dihydroquinine and Its Mechanisms of Action

Huffman, Aarin M.; Ayariga, Joseph A.; Napier, Audrey; Robertson, Boakai K.; Abugri, Daniel A.

doi:10.3389/fcimb.2022.852889

Cited by 11 publications

(9 citation statements)

References 73 publications

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“…ROS are free radicals comprising one or more unpaired electrons, which damage many biomolecules and the cytoarchitecture. Intracellular ROS production will cause mitochondrial DNA, lipids, and protein synthesis disorders (Huffman et al 2022). in addition, artemisinin by heme to induce cytotoxicity to cancer cells is thought to generates damaging ROS (Zhang et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the effect and mechanism of artemether against Toxoplasma gondii

Duan

Pan

et al. 2023

Preprint

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This study aimed to investigate compounds that has anti-Toxoplasma gondii with the possible advantage of limiting drug resistance. Artemether has potential anti-T. gondii activity, however the detail information is not clear. To evaluate the Specific effect and potential mechanism, in this study, the cytotoxicity of artemether was Firstly evaluated using MTT assay. Secondly, the anti-T. gondii activities was determined using plaque assay, and then the invasion and intracellular proliferation were evaluated. Finally, the mitochondrial membrane potential and reactive oxygen species (ROS) of T. gondii were detected by the JC-1 probe and automatic microplate reader. The safe concentration of artemether is below 7.042 mM on HFF cells, and artemether exhibited good anti-T. gondii activity with the IC50 = 0.905 mM, it can inhibit T. gondii intracellular proliferation by decreasing T. gondii mitochondrial membrane integrity and increasing ROS production.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the effect and mechanism of artemether against Toxoplasma gondii

Duan

Pan

et al. 2023

Preprint

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“…6 × 10 4 hTERT cells/200 μL/well were seeded into the flat black bottom 96 well plates and incubated at 37 °C with 5% CO 2 for 24 h 28 . Dead cells were removed by washing three times with 1X Phosphate Buffered Saline (1XPBS).…”

Section: Methodsmentioning

confidence: 99%

“…Media only was used as a negative control. Plates were incubated at 37 °C with 5% CO 2 and read at 48 h using Tecan 200 F infinite microplate reader with excitation/ emission set at 560 nm/635 nm 28 , respectively. The percentage growth of the parasite was calculated with the formulae: (Average fluorescence of control parasitic growth-fluorescence of drug-treated parasitic growth/Average fluorescence of parasitic control growth) × 100.…”

Section: Methodsmentioning

confidence: 99%

“…The percentage growth of the parasite was calculated with the formulae: (Average fluorescence of control parasitic growth-fluorescence of drug-treated parasitic growth/Average fluorescence of parasitic control growth) × 100. The percent inhibition was determined using the procedure reported by Huffman et al 28 . Experiments were performed in quadruple (n = 4) with three independent wells each per experiment.…”

Section: Methodsmentioning

confidence: 99%

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Anti-Toxoplasma gondii activity of Trametes versicolor (Turkey tail) mushroom extract

Sharma,

Catrett,

Nwokeocha

et al. 2023

Sci Rep

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Toxoplasma gondii (T. gondii) infection continues to rise globally in humans and animals with high socioeconomic and public health challenges. Current medications used against T. gondii infection are limited in efficacy, safety, and affordability. This research was conducted to assess the higher fungi extract effect on T. gondii tachyzoites growth in vitro and possibly decipher its mechanism of action. Furthermore, we evaluated the extract's effect on human foreskin fibroblast viability. The methanol extracts of Turkey tail (TT) mushroom was tested against T. gondii tachyzoites growth using an RH-RFP type I strain that expresses red fluorescent protein throughout culture in a dose-dependent manner using a fluorescent plate reader. Similarly, we tested the effect of the extract on host cell viability. We observed that TT extract inhibited tachyzoites growth with a 50% minimum inhibitory concentration (IC50s), IC50 = 5.98 ± 1.22 µg/mL, and 50% cytotoxic concentration (CC50s), CC50 ≥ 100 µg/mL. It was discovered that TT extract induced strong mitochondria superoxide and reactive oxygen species production and disrupted mitochondria membrane potential in T. gondii tachyzoites. Additionally, scanning electron microscopy depicted that TT extract and pyrimethamine (PY) caused a morphological deformation of tachyzoites in vitro. In conclusion, TT methanol extract made up of phytosterols, bioactive sphingolipids, peptides, phenolic acids, and lactones could be a promising source of new compounds for the future development of anti-Toxoplasma gondii drugs. Extracts were non-cytotoxic, even at higher concentrations.

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“…Most of the time, Apicomplexa are motile, and the smooth gliding of the Apicomplexa is carried out through a mechanism that uses small static myosin motors and adhesions (1). The smooth gliding capacity enables the parasite to navigate across substrates, migrate, invade tissues, then egress from one infected cell to another susceptible cell (2). The apical complex of Apicomplexa are structures and secretory organelles which consists of various components that are required for the invasion of host cells during the various stages of the life cycle of the organism (3).…”

Section: Introductionmentioning

confidence: 99%

Review of Lipid Metabolic Pathways and Calcium Signaling in the Apicomplexan Families and their Importance in Drug Discovery

Ayariga¹,

Ibrahim²,

Syamala³

et al. 2023

Preprint

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Calcium signaling and lipid metabolism are crucial in the infection processes of Apicomplexans parasites. Thus, enzymes involved in these processes can be drug targets against Apicomplexans. For example, in malaria infection, in-depth research into lipid metabolic pathways is crucial in understanding the parasite's infection cycle, particularly during its erythrocytic infection cycle, which has been demonstrated to be a critical stage during the disease progression. Most enzymes that play critical roles in lipid synthesis and calcium signaling have been extensively studied; nonetheless, a vast knowledge gap still exists, especially on specific enzymes and their roles in the transmission and progression of the Apicomplexan parasites. Many types of infections caused by Apicomplexans are life-threatening and hard to treat. These intracellular parasites proliferate within parasitophorous vacuoles in their host cells. As the parasites multiply, they need to meet their high demand for nutrients such as amino acids and lipids. They can acquire nutrients through scavenging and biosynthesis. This review summarizes a few interesting, unique pathways in selected Apicomplexa and how such unique pathways can be targets for drugs.

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Inhibition of Toxoplasma gondii Growth by Dihydroquinine and Its Mechanisms of Action

Cited by 11 publications

References 73 publications

Evaluation of the effect and mechanism of artemether against Toxoplasma gondii

Evaluation of the effect and mechanism of artemether against Toxoplasma gondii

Anti-Toxoplasma gondii activity of Trametes versicolor (Turkey tail) mushroom extract

Review of Lipid Metabolic Pathways and Calcium Signaling in the Apicomplexan Families and their Importance in Drug Discovery

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