Myrislignan Induces Redox Imbalance and Activates Autophagy in Toxoplasma gondii

Abstract

Toxoplasma gondii (T. gondii) is an important health problem in human and animals, and the highlighting side effects of launched therapeutic chemicals cannot be ignored. Thus, it is urgent to develop new drugs to against the infection. Myrislignan originated from nutmeg exhibited excellent anti-T. gondii activity in vitro and in vivo, and was able to destroy mitochondrial function. However, the exact mechanism of action is still unknown. In this study, combining RNAs deep-sequencing analysis and surface plasmon resonance (SPR) analysis, the differentially expressed genes (DEGs) and high affinity proteins suggested that myrislignan may affect the oxidation-reduction process of T. gondii. Furthermore, the upregulating ROS activity after myrislignan incubation verified that myrislignan destroyed the oxidant-antioxidant homeostasis of tachyzoites. Transmission electron microscopy (TEM) indicated that myrislignan induced the formation of autophagosome-like double-membrane structure. Moreover, monodansyl cadaverine (MDC) staining and western blot further illustrated autophagosome formation. Myrislignan treatment induced a significant reduction in T. gondii by flow cytometry analysis. Together, these findings demonstrated that myrislignan can induce the oxidation-reduction in T. gondii, lead to the autophagy, and cause the death of T. gondii.

Modulation of autophagy as a therapeutic strategy for Toxoplasma gondii infection

“…In one study myrislignan originating from nutmeg induced a redox imbalance in T. gondii, which led to the autophagic killing of T. gondii (Zhang et al, 2021a). With respect to the underlying mechanisms, myrislignan can lower the mitochondrial membrane potential as well as ATP levels in T. gondii and disrupt mitochondrial function (Zhang et al, 2021a). In another study, Jili-Zhang et al found that licarin-B from nutmeg exhibits excellent anti-T. gondii activity by inducing mitochondrial swelling and nuclear disintegration (Zhang et al, 2021b).…”

“…Methods to facilitate oxidative stress is worthy of future research. In one study myrislignan originating from nutmeg induced a redox imbalance in T. gondii , which led to the autophagic killing of T. gondii ( Zhang et al., 2021a ). With respect to the underlying mechanisms, myrislignan can lower the mitochondrial membrane potential as well as ATP levels in T. gondii and disrupt mitochondrial function ( Zhang et al., 2021a ).…”

Progesterone Can Directly Inhibit the Life Activities of Toxoplasma gondii In Vitro through the Progesterone Receptor Membrane Component (PGRMC)

“…The results showed that, under normal circumstances, RHΔ ku80 tachyzoites contained well-organized organelles. By contrast, RHΔ ku80 tachyzoites were often deformed, vacuolized, and showed many autophagic vacuoles emerging in the cytoplasm after 3 hours of 10 −5 M progesterone treatment [ 22 ] ( Figure 3 c).…”

Evaluation of the effect and mechanism of artemether against Toxoplasma gondii

“…Moreover, mitochondria are "little power stations", which are important organelles to supply energy to support the host cells. The mitochondrial electron transport chain (ETC) is an essential pathway for providing energy and participating in oxidation-reduction process of T. gondii (Zhang et al 2021). However, random disorders of mitochondria due to diabetes or other disadvantages can cause major disruption of metabolism that releases ROS (Tsuda et al 2018).…”