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

Jia-Hui Cheng; Xiang Xu; Ying-Biao Li; Xu-Dong Zhao; Fumie Aosai; Su-Yun Shi; Cheng-Hua Jin; Jing-Shu Piao; Juan Ma; Hu-Nan Piao; Xue-Jun Jin; Lian-Xun Piao

doi:10.1016/j.intimp.2020.106302

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

Int Immunopharmacol. 2020 Feb 18:82:106302. doi: 10.1016/j.intimp.2020.106302. Online ahead of print.

Authors

Jia-Hui Cheng¹, Xiang Xu¹, Ying-Biao Li², Xu-Dong Zhao¹, Fumie Aosai³, Su-Yun Shi¹, Cheng-Hua Jin¹, Jing-Shu Piao¹, Juan Ma¹, Hu-Nan Piao⁴, Xue-Jun Jin⁵, Lian-Xun Piao⁶

Affiliations

¹ Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China.
² Department of Neurology, Affliated Hospital of Yanbian University, Yanji 133000, Jilin, China.
³ Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University, Matsumoto, Japan.
⁴ Department of Neurology, Affliated Hospital of Yanbian University, Yanji 133000, Jilin, China. Electronic address: yhnpiao@163.com.
⁵ Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China. Electronic address: xjjin@ybu.edu.cn.
⁶ Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China. Electronic address: https://orcid.org/0000-0002-8315-5918.

PMID: 32086097
DOI: 10.1016/j.intimp.2020.106302

Abstract

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.

Keywords: Arctigenin; Depression-like behavior; Microglia; Neuroinflammation; Toxoplasma gondii.