Quercetin inhibits Toxoplasma gondii tachyzoite proliferation and acts synergically with azithromycin

Parasites & Vectors

Research

Joseph A. Ayariga¹  Audrey Napier¹  Boakai K. Robertson²  Sandani V. T. Wijerathne²  Daniel A. Abugri³  Homa Nath Sharma³ 

[1] Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, 36104, Montgomery, AL, USA;Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, 36104, Montgomery, AL, USA;Microbiology PhD Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, 36104, Montgomery, AL, USA;Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, 36104, Montgomery, AL, USA;Microbiology PhD Program, Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, 36104, Montgomery, AL, USA;Laboratory of Ethnomedicine, Parasitology and Drug Discovery, College of Science, Technology, Engineering and Mathematics, Alabama State University, 36104, Montgomery, AL, USA;

关键词: Quercetin;    Azithromycin;    Combination;    Synergizes;    Inhibition;    Toxoplasma gondii;    Growth;   

DOI  :  10.1186/s13071-023-05849-3

 received in 2023-02-09, accepted in 2023-06-26,  发布年份 2023

来源: Springer

【 摘 要 】

Quercetin (QUE) is a natural polyphenol known to have numerous pharmacological properties against infectious and non-infectious diseases. Azithromycin (AZ) is an antibiotic that belongs to the azalide class of antimicrobials and an antiparasitic that is known to be effective in combination with clindamycin against pyrimethamine/sulfadiazine-resistant Toxoplasma gondii tachyzoites in clinical settings. Both compounds are known to target protein synthesis and have anti-inflammatory properties. However, little is known about QUE and AZ synergistic interaction against T. gondii growth. Here, we report for the first time the effects of the combination of QUE and AZ on T. gondii growth. The 50% inhibitory concentration (IC50) for QUE at 72 h of interaction was determined to be 0.50 µM, whereas AZ gave an IC50 value of 0.66 µM at 72 h of interaction with parasites. Combination testing of QUE and AZ in a ratio of 2:1 (QUE:AZ) showed an IC50 value of 0.081 µM. Interestingly, a fractional inhibitory index value of 0.28 was observed, indicating a strong synergy. QUE was also found to upregulate the generation of reactive oxygen species and cause dysfunction of the mitochondria membrane of both intracellular and extracellular T. gondii tachyzoites. Overall, the results indicate that QUE is a novel lead capable of synergizing with AZ for inhibiting T. gondii growth and may merit future investigation in vivo for possible combination drug development.Graphical Abstract

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 4

Fig. 11

Fig. 4

Fig. 3

Fig. 4

Fig. 6