Glabridin exhibits potent inhibitory effects against Toxoplasma gondii in vitro and in vivo
Abstract Background Toxoplasma gondii is an obligate protozoan parasite capable of infecting a wide range of warm-blooded animals and humans. Current treatment options, primarily pyrimethamine and sulfadiazine, have limitations, such as high recurrence rates, long treatment durations, and limited ef...
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BMC
2024-12-01
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| Series: | Parasites & Vectors |
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| Online Access: | https://doi.org/10.1186/s13071-024-06610-0 |
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| author | Lu Wang Bintao Zhai Chen Wang Hany M. Elsheikha Haiting Guo Xiao-Nan Zheng Chun‑Xue Zhou Xing-Quan Zhu |
| author_facet | Lu Wang Bintao Zhai Chen Wang Hany M. Elsheikha Haiting Guo Xiao-Nan Zheng Chun‑Xue Zhou Xing-Quan Zhu |
| author_sort | Lu Wang |
| collection | DOAJ |
| description | Abstract Background Toxoplasma gondii is an obligate protozoan parasite capable of infecting a wide range of warm-blooded animals and humans. Current treatment options, primarily pyrimethamine and sulfadiazine, have limitations, such as high recurrence rates, long treatment durations, and limited effectiveness against T. gondii. There is an unmet need for novel, safe, low-toxicity, and highly effective treatments. This study aimed to evaluate the anti-T. gondii effects of glabridin, a natural compound derived from the roots of a widely used medicinal plant. Methods The cytotoxicity of glabridin in Vero cells was assessed using a CCK-8 cell viability assay. Quantitative polymerase chain reaction (qPCR) targeting the Tg-529 gene was developed to quantify T. gondii and assess the inhibitory effects of glabridin on parasite proliferation. Ultrastructural changes in T. gondii after treatment were examined using electron microscopy. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were examined to assess the effects of glabridin on ROS levels and ΔΨm in T. gondii tachyzoites. Additionally, metabolomics and transcriptomics analyses were conducted to investigate the mechanisms underlying glabridin’s anti-T. gondii effects. Results Glabridin exhibited low toxicity to host cells and effectively inhibited T. gondii invasion and proliferation in vitro in a time-dependent manner. Glabridin-treated tachyzoites exhibited significant structural alterations, along with increased ROS production and a reduction in ΔΨm. Metabolomic analysis indicated that glabridin significantly affected amino acid metabolism pathways in T. gondii. In vivo, glabridin treatment significantly improved survival rates in T. gondii-infected BALB/c mice at a dosage of 100 mg/kg. Conclusions This study demonstrates that glabridin has potent anti-T. gondii effects in vitro and in vivo, likely through disruption of amino acid metabolism in the parasite. These findings highlight glabridin’s potential as a promising therapeutic agent for toxoplasmosis. Graphical abstract |
| format | Article |
| id | doaj-art-b6b90a025a414987a465cfbc707b3e2d |
| institution | Kabale University |
| issn | 1756-3305 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj-art-b6b90a025a414987a465cfbc707b3e2d2024-12-22T12:18:16ZengBMCParasites & Vectors1756-33052024-12-0117111110.1186/s13071-024-06610-0Glabridin exhibits potent inhibitory effects against Toxoplasma gondii in vitro and in vivoLu Wang0Bintao Zhai1Chen Wang2Hany M. Elsheikha3Haiting Guo4Xiao-Nan Zheng5Chun‑Xue Zhou6Xing-Quan Zhu7Laboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural UniversityKey Laboratory of Veterinary Pharmaceutical Development, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Ministry of Agriculture and Rural AffairsLaboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural UniversityFaculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of NottinghamLaboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural UniversityLaboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural UniversityDepartment of Pathogen Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityLaboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural UniversityAbstract Background Toxoplasma gondii is an obligate protozoan parasite capable of infecting a wide range of warm-blooded animals and humans. Current treatment options, primarily pyrimethamine and sulfadiazine, have limitations, such as high recurrence rates, long treatment durations, and limited effectiveness against T. gondii. There is an unmet need for novel, safe, low-toxicity, and highly effective treatments. This study aimed to evaluate the anti-T. gondii effects of glabridin, a natural compound derived from the roots of a widely used medicinal plant. Methods The cytotoxicity of glabridin in Vero cells was assessed using a CCK-8 cell viability assay. Quantitative polymerase chain reaction (qPCR) targeting the Tg-529 gene was developed to quantify T. gondii and assess the inhibitory effects of glabridin on parasite proliferation. Ultrastructural changes in T. gondii after treatment were examined using electron microscopy. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were examined to assess the effects of glabridin on ROS levels and ΔΨm in T. gondii tachyzoites. Additionally, metabolomics and transcriptomics analyses were conducted to investigate the mechanisms underlying glabridin’s anti-T. gondii effects. Results Glabridin exhibited low toxicity to host cells and effectively inhibited T. gondii invasion and proliferation in vitro in a time-dependent manner. Glabridin-treated tachyzoites exhibited significant structural alterations, along with increased ROS production and a reduction in ΔΨm. Metabolomic analysis indicated that glabridin significantly affected amino acid metabolism pathways in T. gondii. In vivo, glabridin treatment significantly improved survival rates in T. gondii-infected BALB/c mice at a dosage of 100 mg/kg. Conclusions This study demonstrates that glabridin has potent anti-T. gondii effects in vitro and in vivo, likely through disruption of amino acid metabolism in the parasite. These findings highlight glabridin’s potential as a promising therapeutic agent for toxoplasmosis. Graphical abstracthttps://doi.org/10.1186/s13071-024-06610-0Toxoplasma gondiiGlabridinMetabolomicsTranscriptomicsSurvival rate |
| spellingShingle | Lu Wang Bintao Zhai Chen Wang Hany M. Elsheikha Haiting Guo Xiao-Nan Zheng Chun‑Xue Zhou Xing-Quan Zhu Glabridin exhibits potent inhibitory effects against Toxoplasma gondii in vitro and in vivo Parasites & Vectors Toxoplasma gondii Glabridin Metabolomics Transcriptomics Survival rate |
| title | Glabridin exhibits potent inhibitory effects against Toxoplasma gondii in vitro and in vivo |
| title_full | Glabridin exhibits potent inhibitory effects against Toxoplasma gondii in vitro and in vivo |
| title_fullStr | Glabridin exhibits potent inhibitory effects against Toxoplasma gondii in vitro and in vivo |
| title_full_unstemmed | Glabridin exhibits potent inhibitory effects against Toxoplasma gondii in vitro and in vivo |
| title_short | Glabridin exhibits potent inhibitory effects against Toxoplasma gondii in vitro and in vivo |
| title_sort | glabridin exhibits potent inhibitory effects against toxoplasma gondii in vitro and in vivo |
| topic | Toxoplasma gondii Glabridin Metabolomics Transcriptomics Survival rate |
| url | https://doi.org/10.1186/s13071-024-06610-0 |
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