2. Academic Validation
  3. Glabridin exhibits potent inhibitory effects against Toxoplasma gondii in vitro and in vivo

Glabridin exhibits potent inhibitory effects against Toxoplasma gondii in vitro and in vivo

  • Parasit Vectors. 2024 Dec 18;17(1):522. doi: 10.1186/s13071-024-06610-0.
Lu Wang 1,  Bintao Zhai 2,  Chen Wang 1,  Hany M Elsheikha 3,  Haiting Guo 1 4,  Xiao-Nan Zheng 1,  Chun-Xue Zhou 5,  Xing-Quan Zhu 6
Affiliations

Affiliations

  • 1 Laboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi Province, 030801, People's Republic of China.
  • 2 Key Laboratory of Veterinary Pharmaceutical Development, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Ministry of Agriculture and Rural Affairs, Lanzhou, Gansu Province, 730050, People's Republic of China.
  • 3 Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.
  • 4 Guangxi Key Laboratory of Brain and Cognitive Neuroscience, College of Basic Medicine, Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, 541199, People's Republic of China.
  • 5 Department of Pathogen Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, 250012, People's Republic of China. zhouchunxue23@163.com.
  • 6 Laboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi Province, 030801, People's Republic of China. xingquanzhu1@hotmail.com.
PMID: 39695816 DOI: 10.1186/s13071-024-06610-0
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.

Keywords

Toxoplasma gondii; Glabridin; Metabolomics; Survival rate; Transcriptomics.

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