Licochalcone A: An effective and low-toxicity compound against Toxoplasma gondii in vitro and in vivo

Toxoplasma gondii, an obligate intracellular protozoan, is the causative agent of toxoplasmosis, which can cause serious public health problems. The current drugs used to treat toxoplasmosis have many limitations. This study evaluated the anti-T. gondii activity and potential mechanism of Licochalco...

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Main Authors: Hongfei Si, Chunyan Xu, Jili Zhang, Xukun Zhang, Bing Li, Xuzheng Zhou, Jiyu Zhang
Format: Article
Language:English
Published: Elsevier 2018-08-01
Series:International Journal for Parasitology: Drugs and Drug Resistance
Online Access:http://www.sciencedirect.com/science/article/pii/S2211320717301112
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author Hongfei Si
Chunyan Xu
Jili Zhang
Xukun Zhang
Bing Li
Xuzheng Zhou
Jiyu Zhang
author_facet Hongfei Si
Chunyan Xu
Jili Zhang
Xukun Zhang
Bing Li
Xuzheng Zhou
Jiyu Zhang
author_sort Hongfei Si
collection DOAJ
description Toxoplasma gondii, an obligate intracellular protozoan, is the causative agent of toxoplasmosis, which can cause serious public health problems. The current drugs used to treat toxoplasmosis have many limitations. This study evaluated the anti-T. gondii activity and potential mechanism of Licochalcone A (Lico A) in vitro and in vivo. The safe concentration of Lico A in HFF cells was determined by MTT cell viability assays. The presence of T. gondii was assessed by qPCR and Giemsa staining. Azithromycin and sulfadiazine, commonly used effective treatments, served as drug controls. T. gondii ultrastructural alterations were observed by electron microscopy. The anti-T. gondii activity of Lico A was evaluated using an in vivo mouse infection model. In vitro, Lico A had no negative effect on host cell viability at concentrations below 9 μg/mL; however, it did inhibit T. gondii proliferation in a dose-dependent manner, with a 50% inhibitory concentration (IC50) of 0.848 μg/mL. Electron microscopy analyses indicated substantial structural and ultrastructural changes in tachyzoites after Lico A treatment. Nile Red staining assays demonstrated that Lico A caused lipid accumulation. Lico A treatment significantly increased the survival rate of BALB/c mice infected with T. gondii. Lico A achieved the same therapeutic effect as a commonly used clinical drugs (combination of sulfadiazine, pyrimethamine and folinic acid). In conclusion, Lico A has strong anti-T. gondii activity in vitro and in vivo and might be developed into a new anti-T. gondii drug. Moreover, Lico A may exert these effects by interfering with lipid metabolism in the parasite. Keywords: Licochalcone A, Anti-Toxoplasma gondii, Ultrastructural, Cytotoxicity, Survival curve
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spelling doaj.art-9f4f1da9be9e4ab597c0282f3fd1139d2022-12-21T23:49:10ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072018-08-0182238245Licochalcone A: An effective and low-toxicity compound against Toxoplasma gondii in vitro and in vivoHongfei Si0Chunyan Xu1Jili Zhang2Xukun Zhang3Bing Li4Xuzheng Zhou5Jiyu Zhang6College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang, China; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, Gansu, ChinaCollege of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaLanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, Gansu, ChinaCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110000, ChinaLanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, Gansu, ChinaLanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, Gansu, ChinaCollege of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang, China; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, Gansu, China; Corresponding author. Lanzhou Institute of Animal Science and Veterinary Pharmaceutics, Chinese Academy of Agricultural Sciences, 335 Jiangouyan, Qilihe, Lanzhou 730050, Gansu, China.Toxoplasma gondii, an obligate intracellular protozoan, is the causative agent of toxoplasmosis, which can cause serious public health problems. The current drugs used to treat toxoplasmosis have many limitations. This study evaluated the anti-T. gondii activity and potential mechanism of Licochalcone A (Lico A) in vitro and in vivo. The safe concentration of Lico A in HFF cells was determined by MTT cell viability assays. The presence of T. gondii was assessed by qPCR and Giemsa staining. Azithromycin and sulfadiazine, commonly used effective treatments, served as drug controls. T. gondii ultrastructural alterations were observed by electron microscopy. The anti-T. gondii activity of Lico A was evaluated using an in vivo mouse infection model. In vitro, Lico A had no negative effect on host cell viability at concentrations below 9 μg/mL; however, it did inhibit T. gondii proliferation in a dose-dependent manner, with a 50% inhibitory concentration (IC50) of 0.848 μg/mL. Electron microscopy analyses indicated substantial structural and ultrastructural changes in tachyzoites after Lico A treatment. Nile Red staining assays demonstrated that Lico A caused lipid accumulation. Lico A treatment significantly increased the survival rate of BALB/c mice infected with T. gondii. Lico A achieved the same therapeutic effect as a commonly used clinical drugs (combination of sulfadiazine, pyrimethamine and folinic acid). In conclusion, Lico A has strong anti-T. gondii activity in vitro and in vivo and might be developed into a new anti-T. gondii drug. Moreover, Lico A may exert these effects by interfering with lipid metabolism in the parasite. Keywords: Licochalcone A, Anti-Toxoplasma gondii, Ultrastructural, Cytotoxicity, Survival curvehttp://www.sciencedirect.com/science/article/pii/S2211320717301112
spellingShingle Hongfei Si
Chunyan Xu
Jili Zhang
Xukun Zhang
Bing Li
Xuzheng Zhou
Jiyu Zhang
Licochalcone A: An effective and low-toxicity compound against Toxoplasma gondii in vitro and in vivo
International Journal for Parasitology: Drugs and Drug Resistance
title Licochalcone A: An effective and low-toxicity compound against Toxoplasma gondii in vitro and in vivo
title_full Licochalcone A: An effective and low-toxicity compound against Toxoplasma gondii in vitro and in vivo
title_fullStr Licochalcone A: An effective and low-toxicity compound against Toxoplasma gondii in vitro and in vivo
title_full_unstemmed Licochalcone A: An effective and low-toxicity compound against Toxoplasma gondii in vitro and in vivo
title_short Licochalcone A: An effective and low-toxicity compound against Toxoplasma gondii in vitro and in vivo
title_sort licochalcone a an effective and low toxicity compound against toxoplasma gondii in vitro and in vivo
url http://www.sciencedirect.com/science/article/pii/S2211320717301112
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