Cheng Jia-Hui, Xu Xiang, Li Ying-Biao, Zhao Xu-Dong, Aosai Fumie, Shi Su-Yun, Jin Cheng-Hua, Piao Jing-Shu, Ma Juan, Piao Hu-Nan, Jin Xue-Jun, Piao Lian-Xun
Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, Jilin, China.
Department of Neurology, Affliated Hospital of Yanbian University, Yanji 133000, Jilin, China.
Int Immunopharmacol. 2020 Feb 18;82:106302. doi: 10.1016/j.intimp.2020.106302.
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.
弓形虫是一种已知的嗜神经原虫，它寄留在中枢神经系统并在中间宿主体内引发神经精神疾病。牛蒡子苷元（AG）是牛蒡果实的主要生物活性木脂素之一，具有广泛的药理活性，如神经保护、抗炎和抗弓形虫作用。然而，AG对弓形虫感染宿主中观察到的抑郁行为的影响尚未阐明。在本研究中，我们使用小胶质细胞系（BV2细胞）和感染弓形虫RH株急性期的BALB/c小鼠脑组织，分析了AG对弓形虫诱导的中间宿主体内抑郁行为的影响。AG通过Toll样受体/核因子-κB（NF-κB）和肿瘤坏死因子受体1/NF-κB信号通路减轻小胶质细胞活化和神经炎症，随后上调多巴胺和5-羟色胺水平并抑制宿主类似抑郁的行为。AG还显著降低了小鼠脑组织中的弓形虫负荷。总之，我们阐明了AG对弓形虫感染诱导的抑郁行为的影响及其潜在的分子机制。
