Myrislignan

31620108

Toxoplasma gondii is a widespread obligatory parasitic protozoon that infects nearly all warm-blooded animals and causes toxoplasmosis. However, the current treatments for toxoplasmosis are limited by severe side effects. Myrislignan is a natural product from Myristica fragrans Houtt with wide pharmacological activities. In the current study, we tested the anti-T. gondii activity of myrislignan both in vitro and in vivo and explored its potential mechanism of action. The cytotoxicity of myrislignan in African green monkey kidney (Vero) cells was assessed using Cell Counting Kit-8 (CCK-8) assays. The in vitro effects of myrislignan on T. gondii were determined by quantitative PCR and Giemsa staining. An in vivo murine model of T. gondii infection was used to determine the efficacy of myrislignan. The changes in tachyzoites after myrislignan exposure were examined by electron microscopy. The impact of myrislignan on mitochondrial function in tachyzoites was assessed by MitoTracker Red CMXRos staining and an ATP detection kit. In vitro, myrislignan inhibited T. gondii tachyzoite proliferation with a 50% effective concentration of 32.41 μg/ml, and reduced the invasion of cells by tachyzoites (14.63 and 1.92% invasion rates for control and 70 μg/ml myrislignan, respectively). Importantly, myrislignan had no significant cytotoxicity against Vero cells at concentrations less than 132 μg/ml. In addition, surface shrinkage and mitochondrial damage were observed in tachyzoites after myrislignan exposure. The reduced ΔΨm and ATP levels in tachyzoites treated with myrislignan further confirmed mitochondrial damage. In the in vivo murine model, myrislignan treatment significantly reduced the parasite burden in tissues compared to no treatment. In conclusion, myrislignan had potent anti-T. gondii activities both in vitro and in vivo, and these activities might involve the interruption of mitochondrial function. These data suggest that myrislignan might be a useful compound for the treatment of toxoplasmosis.

Copyright © 2019 Zhang, Si, Li, Zhou and Zhang.

T. gondii; in vitro; in vivo; mechanism(s) of action; myrislignan

Myrislignan Exhibits Activities Against Toxoplasma gondii RH Strain by Triggering Mitochondrial Dysfunction.

Zhang J1,2,3, Si H4, Li B1,2,3, Zhou X1,2,3, Zhang J1,2,3.

2019 Sep 18

27491743

Myrislignan is a natural compound with little pharmacological study. In our investigation, we investigated the effect of myrislignan in the induction of apoptosis in A549 cells in vitro and in vivo. Myrislignan inhibited the proliferation of A549 cells in a dose- and time-dependent manner assayed by MTT. In addition, Hoechst flow cytometry showed that myrislignan significantly induced apoptosis and cell cycle arrest in A549 cells. The apoptosis and anti-cell proliferation was mediated by the activation of mitogen-activated protein kinase and the inhibition of epidermal growth factor receptor signal pathway, change of mitochondrial membrane potential, the releasing of c-Myc, the downregulation of the level of the anti-apoptotic protein Bcl-2, and the upregulation of the level of the pro-apoptotic protein Bax. In conclusion, those results reveal a potential mechanism for the anti-cancer effect of myrislignan on human lung cancer, while suggesting that myrislignan may be a promising compound for the treatment of lung cancer.

Apoptosis; Cell cycle arrest; EGFR-MAPK; Human lung cancer cells; Myrislignan

The action and mechanism of myrislignan on A549 cells in vitro and in vivo.

Lu X1, Yang L2, Chen J3, Zhou J4, Tang X4, Zhu Y4, Qiu H1, Shen J5.

2017 Jan;