Jing Haoran, Wang Shaoxia, Wang Min, Fu Wenliang, Zhang Chao, Xu Donggang
Laboratory of Genome Engineering, The Beijing Institute of Basic Medical Sciences, Beijing, China.
Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.
PLoS One. 2017 Jan 6;12(1):e0169560. doi: 10.1371/journal.pone.0169560. eCollection 2017.
Parkinson's disease (PD) is a complex multi-system and age-related neurodegenerative disorder. The intervention targeting neuroinflammation in PD patients is one effective strategy to slow down or inhibit disease progression. Microglia-mediated inflammatory response plays an important role in Parkinson's, Alzheimer's and other cerebral diseases. Isobavachalcone is a main component of Chinese herb medicine Psoralea corylifolia, which function includes immunoregulation, anti-oxidation and the regulation of β-amyloid (Aβ42) deposited in hippocampus in Alzheimer's patients. Whether it has the therapeutic effect on Parkinson's disease, however, is unclear. In this study, we found that isobavachalcone could effectively remit Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), prolong the residence time of mice on Rota-rod and alleviate the neuronal necrosis. It also inhibited the over-activation of microglia, and decreased the expression of IL-6 and IL-1β in the brain of PD mice. In vitro, isobavachalcone could inhibit nuclear factor-kappaB (NF-κB) pathway through inhibiting the LPS-induced transfer of NF-κB subunit from cytoplasm to nucleus in BV-2 cells. Isobavachalcone decreased the LPS-induced oxidative stress and the expression of inflammatory cytokines, and provided a neuroprotective effect by antagonizing microglia-mediated inflammation. Our results indicated that isobavachalcone may be a candidated drug against Parkinson's disease with great clinical potential.
帕金森病（PD）是一种复杂的多系统且与年龄相关的神经退行性疾病。针对帕金森病患者神经炎症的干预是减缓或抑制疾病进展的一种有效策略。小胶质细胞介导的炎症反应在帕金森病、阿尔茨海默病和其他脑部疾病中起重要作用。异补骨脂查耳酮是中药补骨脂的主要成分，其功能包括免疫调节、抗氧化以及调节阿尔茨海默病患者海马体中沉积的β-淀粉样蛋白（Aβ42）。然而，它对帕金森病是否具有治疗作用尚不清楚。在本研究中，我们发现异补骨脂查耳酮可有效缓解1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森病，延长小鼠在转棒上的停留时间并减轻神经元坏死。它还抑制小胶质细胞的过度激活，并降低帕金森病小鼠脑中白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）的表达。在体外，异补骨脂查耳酮可通过抑制脂多糖（LPS）诱导的NF-κB亚基从细胞质转移至细胞核，从而抑制BV-2细胞中的核因子-κB（NF-κB）通路。异补骨脂查耳酮降低了LPS诱导的氧化应激和炎性细胞因子的表达，并通过拮抗小胶质细胞介导的炎症提供神经保护作用。我们的结果表明，异补骨脂查耳酮可能是一种具有巨大临床潜力的抗帕金森病候选药物。
