Depression and anxiety are common neuropsychiatric symptom of Parkinson's disease (PD), reflecting reduced quality of life in patients with PD. Silibinin (silybin), a flavonoid extracted and isolated from the fruit of Silybum marianum (L.) Gaertn, is widely used for the treatment of hepatic diseases. We report here that silibinin shows anti-depressant and anti-anxiety effects on 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model mice with PD. All the results of open field test, elevated plus maze test, tail suspension test and forced swimming test demonstrated that silibinin administration significantly attenuated MPTP-induced depression/anxiety. Hematoxylin-eosin (HE) staining and Nissl staining results showed that MPTP injection caused the damage of hippocampal neurons, but this was ameliorated by oral administration of silibinin. Silibinin significantly restored hippocampal levels of 5-hydroxyptramine (5-HT) and noradrenaline (NA), two important neurotransmitters for regulating mood, which decreased in MPTP-injected mice. Neuroinflammation, as reflected by the increased expressions of IL-1β, TNFα and IFN-β, was marked in the hippocampus of MPTP-treated mice, accompanying increased stimulator of interferon genes (STING) and interferon regulatory factor-3 (IRF3). Silibinin administration, however, down-regulated the levels of IL-1β, TNFα and IFN-β, as well as STING and IRF3, protecting MPTP-induced PD model mice. These findings indicate that silibinin has a potential of being further developed as a therapeutic for depression and anxiety in PD.

抑郁和焦虑是帕金森病 (PD) 的常见神经精神症状，反映了 PD 患者生活质量的下降。水飞蓟宾 (silybin)，一种从水飞蓟 ( L. ) Gaertn果实中提取和分离的黄酮类化合物，广泛用于治疗肝病。我们在此报告水飞蓟宾对 1-Methyl-4-phenyl-1,2,3,6-四氢吡啶 (MPTP) 诱导的 PD 模型小鼠具有抗抑郁和抗焦虑作用。野外试验、高架十字迷宫试验、悬尾试验和强迫游泳试验的所有结果表明，水飞蓟宾给药显着减轻了MPTP诱导的抑郁/焦虑。苏木精-伊红(HE)染色和Nissl染色结果显示，注射MPTP会引起海马神经元的损伤，但口服水飞蓟宾可以改善这种损伤。水飞蓟宾显着恢复了海马中 5-羟丙胺 (5-HT) 和去甲肾上腺素 (NA) 的水平，这两种重要的调节情绪的神经递质在注射 MPTP 的小鼠中降低。神经炎症，β、TNF α和 IFN- β在 MPTP 处理的小鼠的海马中被标记，伴随着干扰素基因 (STING) 和干扰素调节因子-3 (IRF3) 的刺激物增加。然而，水飞蓟宾给药会下调 IL-1 β、TNF α和 IFN- β以及 STING 和 IRF3 的水平，从而保护 MPTP 诱导的 PD 模型小鼠。这些发现表明，水飞蓟宾有可能被进一步开发为 PD 抑郁症和焦虑症的治疗剂。