Direct and Indirect Inhibition Effects of Resveratrol against Toxoplasma gondii Tachyzoites In Vitro

Antimicrob Agents Chemother. 2019 Feb 26;63(3):e01233-18. doi: 10.1128/AAC.01233-18. Print 2019 Mar.

Abstract

Toxoplasma gondii is one of the most widespread obligatory parasitic protozoa and infects nearly all warm-blooded animals, leading to toxoplasmosis. The therapeutic drugs currently administered, like the combination of pyrimethamine and sulfadiazine, show high rates of toxic side effects, and drug resistance is encountered in some cases. Resveratrol is a natural plant extract with multiple functions, such as antibacterial, anticancer, and antiparasite activities. In this study, we evaluated the inhibitory effects of resveratrol on tachyzoites of the Toxoplasma gondii RH strain extracellularly and intracellularly. We demonstrate that resveratrol possesses direct antitoxoplasma activity by reducing the population of extracellularly grown tachyzoites, probably by disturbing the redox homeostasis of the parasites. Moreover, resveratrol was also able to release the burden of cellular stress, promote apoptosis, and maintain the autophagic status of macrophages, which turned out to be regulated by intracellular parasites, thereby functioning indirectly in eliminating T. gondii In conclusion, resveratrol has both direct and indirect antitoxoplasma effects against RH tachyzoites and may possess the potential to be further evaluated and employed for toxoplasmosis treatment.

Keywords: Toxoplasma gondii; apicomplexan parasites; host-parasite relationship; intracellular parasites; resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparasitic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line
  • Enzyme Inhibitors / pharmacology*
  • Host-Parasite Interactions / drug effects
  • Humans
  • Macrophages / immunology
  • Mice
  • Plant Extracts / pharmacology
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • Resveratrol / pharmacology*
  • Superoxide Dismutase / metabolism
  • Toxoplasma / drug effects*
  • Toxoplasmosis / drug therapy*

Substances

  • Antiparasitic Agents
  • Enzyme Inhibitors
  • Plant Extracts
  • Reactive Oxygen Species
  • Superoxide Dismutase
  • Resveratrol