Arctigenin exhibits hepatoprotective activity in Toxoplasma gondii-infected host through HMGB1/TLR4/NF-κB pathway.

Toxoplasmosis is a parasitic zoonosis with the highest incidence in humans. Severe lesions due to acute toxoplasmosis have been recorded in the visceral organs including the liver, where hepatocytes and Kupffer cells are important innate immune cells. Arctigenin (AG) is a bioactive ingredient of Arctium lappa L. and increasing evidence suggests that AG exhibits anti-oxidant, anti-inflammatory and anti-Toxoplasma gondii (T. gondii) effects. However, the role of AG in acute liver damage induced by T. gondii infection remains unclear. In this study, we analyzed the effects of AG against T. gondii-induced liver damage by establishing an in vitro infection model using a murine liver cell line (NCTC-1469 cells) and an in vivo mouse model with acute T. gondii infection of virulent RH strain. In the current study, AG effectively attenuated hepatocytes apoptosis and inhibited the reproduction of T. gondii. The results of in vitro and in vivo studies showed that AG significantly reduced alanine aminotransferase/aspartate aminotransferase activities and lessened pathological damage of liver. Moreover, AG suppressed T. gondii-induced inducible nitric oxide synthase production. AG also attenuated liver inflammation by inhibiting T. gondii-induced activation of the high-mobility group box1/toll-like receptor 4/nuclear factor-kappa B (HMGB1/TLR4/NF-κB) signaling pathway. These findings demonstrated that AG exhibited prominent hepatoprotective activities in toxoplasmic liver injury with anti-inflammatory effects by inhibiting the HMGB1/TLR4/NF-κB signaling axis. Thus, this study provides the basis for the development of new drugs to treat toxoplasmic hepatitis.

Arctigenin ameliorates depression-like behaviors in Toxoplasma gondii-infected intermediate hosts via the TLR4/NF-κB and TNFR1/NF-κB signaling pathways.

Toxoplasma gondii (T. gondii) is a known neurotropic protozoan that remains in the central nervous system and induces neuropsychiatric diseases in intermediate hosts. Arctigenin (AG) is one of the major bioactive lignans of the fruit Arctium lappa L. and has a broad spectrum of pharmacological activities such as neuroprotective, anti-inflammatory and anti-T. gondii effects. However, the effect of AG against depressive behaviors observed in T. gondii-infected hosts has not yet been clarified. In the present study, we analyzed the effects of AG against T. gondii-induced depressive behaviors in intermediate hosts using a microglia cell line (BV2 cells) and brain tissues of BALB/c mice during the acute phase of infection with the RH strain of T. gondii. AG attenuated microglial activation and neuroinflammation via the Toll-like receptor/nuclear factor-kappa B (NF-κB) and tumor necrosis factor receptor 1/NF-κB signaling pathways, followed by up-regulating the dopamine and 5-hydroxytryptamine levels and inhibiting the depression-like behaviors of hosts. AG also significantly decreased the T. gondii burden in mouse brain tissues. In conclusion, we elucidated the effects and underlying molecular mechanisms of AG against depressive behaviors induced by T. gondii infection.