Abstract
This study was performed to investigate the mechanism of action of ursolic acid in terms of anti-Toxoplasma gondii effects, including immunomodulatory effects. We evaluated the anti-T. gondii effects of ursolic acid, and analyzed the production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines through co-cultured immune cells, as well as the expression of intracellular organelles of T. gondii. The subcellular organelles and granules of T. gondii, particularly rhoptry protein 18, microneme protein 8, and inner membrane complex sub-compartment protein 3, were markedly decreased when T. gondii was treated with ursolic acid, and their expressions were effectively inhibited. Furthermore, ursolic acid effectively increased the production of NO, ROS, interleukin (IL)-10, IL-12, granulocyte macrophage colony stimulating factor (GM-CSF), and interferon-β, while reducing the expression of IL-1β, IL-6, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-β1) in T. gondii-infected immune cells. These results demonstrate that ursolic acid not only causes anti-T. gondii activity/action by effectively inhibiting the survival of T. gondii and the subcellular organelles of T. gondii, but also induces specific immunomodulatory effects in T. gondii-infected immune cells. Therefore, this study indicates that ursolic acid can be effectively utilized as a potential candidate agent for developing novel anti-toxoplasmosis drugs, and has immunomodulatory activity.
Highlights
Zoonotic diseases have been consistently occurring in different countries worldwide, causing serious threats in many countries and to humans globally
Before evaluating the mechanism of action of ursolic acid against T. gondii, we measured the inhibitory effect of ursolic acid (UA) against the survival of T. gondii and normal lung cells infected with T. gondii through an MTT assay as described previously [9], which showed significant results and reproducibility
The lung cells infected with T. gondii were markedly inhibited in a dose-dependent manner after treatment with ursolic acid (12.5–200 μg/mL) when compared with the untreated infection cells and the T. gondii-infected cells treated with SF (Figure 2)
Summary
Zoonotic diseases have been consistently occurring in different countries worldwide, causing serious threats in many countries and to humans globally. Effective next-generation drugs for treating toxoplasmosis have not yet been developed, and the difficulty of drug development against zoonosis is still causing a public health crisis globally In this context, various studies on the development or discovery of effective drugs and novel candidates against parasitic zoonosis are urgently required. Various studies on the development or discovery of effective drugs and novel candidates against parasitic zoonosis are urgently required In this regard, ursolic acid is a bioactive compound derived from medicinal plants, and is known to have selective bioactive properties such as anti-inflammatory [24,25,26,27] and anticancer effects [28,29,30,31]. This study was performed to evaluate the mechanism of action and the immunomodulatory activity of ursolic acid in terms of anti-T. gondii effects and activity, and to confirm the potential as a potent candidate drug for developing novel anti-toxoplasmosis agents
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