The phytochemical arbutin exerts potent anti-Toxoplasma effects through activation of cell-autonomous defense mechanisms while attenuating inflammation

  • PLoS Negl Trop Dis. 2025 Dec 11;19(12):e0013815. doi: 10.1371/journal.pntd.0013815.
Zhuanzhuan Liu  1  2 ,  Yulu Ma  1  2 ,  Yaoyao Xiang  1  2 ,  Yusi Shen  1  2 ,  Longxiang Liao  1  2 ,  Xiuwen Zhu  1  2 ,  Zhen Shi  1  2 ,  Yanxia Wei  1  2 ,  Yanbo Kou  1  2 ,  Yugang Wang  1  2
Affiliations
  • 1. Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
  • 2. Laboratory of Infection and Immunity, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, China.
PMID: 41379884 DOI: 10.1371/journal.pntd.0013815
Abstract

Background: Plant-derived natural products have emerged as promising candidates for developing novel anti-toxoplasmosis drugs. This study aimed to elucidate the role and mechanism of the phytochemical arbutin in the control of T. gondii Infection.

Methodology/principal findings: The effect of arbutin on T. gondii Infection and host inflammatory response was evaluated both in vitro and in vivo. RNA-seq was performed on mouse bone marrow-derived macrophage samples to identify potential arbutin-related biological processes and molecular targets that control T. gondii Infection. These targets were further confirmed using target-specific activators or inhibitors. Our data indicated that arbutin has dual therapeutic effects against T. gondii Infection through concurrently controlling Parasite growth and mitigating infection-induced inflammation. Mechanistically, arbutin mediates restriction of intracellular labile iron pool in both immune and non-immune cells, thereby depriving the Parasite of essential metal nutrients. In addition, in macrophages, arbutin not only inhibits infection-induced inflammatory response but also upregulates the expression of heme degrading enzyme heme oxygenase-1, which facilitates biliverdin production. Our data further demonstrated that biliverdin exhibits anti-T. gondii effector function. Furthermore, arbutin is also effective in reducing infection-related mortality in immunocompromised mice.

Conclusions/significance: Our data highlight arbutin's potential therapeutic value in fighting against acute hyperinflammatory phase of Toxoplasmosis even in immunocompromised host but also its limitation in establishing long-term immunity. Our study further suggests a potential direction for further development of effective drugs to prevent and treat toxoplasmosis by pharmacologically enhancing cell-autonomous defense mechanisms while suppressing inflammatory response.

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