Abstract：
Parkinson\'s disease (PD) is a neurodegenerative disease caused by the death of dopaminergic neurons in the nigrostriatal pathway, leading to motor and non-motor dysfunctions, such as depression, olfactory dysfunction, and memory impairment. Although levodopa (L-dopa) has been the gold standard PD treatment for decades, it only relieves motor symptoms and has no effect on non-motor symptoms or disease progression. Prior studies have reported that 6-shogaol, the active ingredient in ginger, exerts a protective effect on dopaminergic neurons by suppressing neuroinflammation in PD mice. This study investigated whether cotreatment with 6-shogaol and L-dopa could attenuate both motor and non-motor symptoms and dopaminergic neuronal damage. Both 6-shogaol (20 mg/kg) and L-dopa (80 mg/kg) were orally administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid- induced PD model mice for 26 days. The experimental results showed that L-dopa alleviated motor symptoms, but had no significant effect on non-motor symptoms, loss of dopaminergic neuron, or neuroinflammation. However, when mice were treated with 6-shogaol alone or in combination L-dopa, an amelioration in both motor and non-motor symptoms such as depression-like behavior, olfactory dysfunction and memory impairment was observed. Moreover, 6-shogaol-only or co-treatment with 6-shogaol and L-dopa protected dopaminergic neurons in the striatum and reduced neuroinflammation in the striatum and substantia nigra. Overall, these results suggest that 6-shogaol can effectively complement L-dopa by improving non-motor dysfunction and restoring dopaminergic neurons via suppressing neuroinflammation.
摘要：
帕金森病(PD)是由黑质纹状体途径的多巴胺能神经元死亡引起的神经退行性疾病,导致运动和非运动功能障碍，比如抑郁症，嗅觉功能障碍,和记忆障碍。尽管左旋多巴（L-dopa）几十年来一直是PD治疗的黄金标准，它只能缓解运动症状，对非运动症状或疾病进展没有影响。先前的研究报告说，6-shogaol，生姜中的活性成分，通过抑制PD小鼠的神经炎症对多巴胺能神经元发挥保护作用。这项研究调查了与6-shogaol和L-多巴共同治疗是否可以减轻运动和非运动症状以及多巴胺能神经元损伤。将6-shogaol（20mg/kg）和L-多巴（80mg/kg）均口服给予1-甲基-4-苯基-1,2,3,6-四氢吡啶/丙磺胺诱导的PD模型小鼠26天。实验结果表明，左旋多巴减轻了运动症状，但对非运动症状没有显著影响,多巴胺能神经元丢失，或神经炎症。然而,当小鼠用6-shogaol单独或组合左旋多巴治疗时，改善运动和非运动症状，如抑郁样行为，观察到嗅觉功能障碍和记忆障碍。此外，仅6-shogaol或与6-shogaol和L-多巴共同治疗可保护纹状体中的多巴胺能神经元，并减少纹状体和黑质中的神经炎症。总的来说,这些结果表明，6-shogaol可以通过抑制神经炎症改善非运动功能障碍和恢复多巴胺能神经元来有效补充L-多巴。
