Growth, Development, and Mental Health of Children and Adolescence Center, Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Mol Biol Rep. 2024 Aug 14;51(1):908. doi: 10.1007/s11033-024-09852-4.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by oxidative stress and neuroinflammation. Sofalcone (SFC), a chalcone derivative known for its antioxidative and anti-inflammatory properties, is widely used clinically as a gastric mucosa protective agent. However, its therapeutic potential in PD remains to be fully explored. In this study, we investigated the neuroprotective effects of SFC in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model.
We found that SFC ameliorated MPTP-induced motor impairments in mice, as assessed by the rotarod and wire tests. Moreover, SFC administration prevented the loss of dopaminergic neurons and striatal degeneration induced by MPTP. Subsequent investigations revealed that SFC reversed MPTP-induced downregulation of NRF2, reduced elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased total antioxidant capacity (TAOC). Furthermore, SFC suppressed MPTP-induced activation of microglia and astrocytes, downregulated the pro-inflammatory cytokine TNF-α, and upregulated the anti-inflammatory cytokine IL-4. Additionally, SFC ameliorated the MPTP-induced downregulation of phosphorylation of Akt at Ser473.
This study provides evidence for the neuroprotective effects of SFC, highlighting its antioxidative and anti-inflammatory properties and its role in Akt activation in the PD model. These findings underscore SFC's potential as a promising therapeutic candidate for PD, warranting further clinical investigation.
帕金森病（PD）是一种进行性神经退行性疾病，其特征是氧化应激和神经炎症。水飞蓟宾（SFC）是一种查耳酮衍生物，具有抗氧化和抗炎特性，临床上广泛用作胃黏膜保护剂。然而，其在 PD 中的治疗潜力仍有待充分探索。在这项研究中，我们研究了 SFC 在 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的 PD 小鼠模型中的神经保护作用。
我们发现 SFC 改善了 MPTP 诱导的小鼠运动障碍，通过转棒和线测试进行评估。此外，SFC 给药可防止 MPTP 诱导的多巴胺能神经元丧失和纹状体变性。进一步的研究表明，SFC 逆转了 MPTP 诱导的 NRF2 下调，降低了升高的活性氧（ROS）和丙二醛（MDA）水平，并增加了总抗氧化能力（TAOC）。此外，SFC 抑制了 MPTP 诱导的小胶质细胞和星形胶质细胞的激活，下调了促炎细胞因子 TNF-α，并上调了抗炎细胞因子 IL-4。此外，SFC 改善了 MPTP 诱导的 Akt 在 Ser473 磷酸化的下调。
这项研究为 SFC 的神经保护作用提供了证据，强调了其抗氧化和抗炎特性以及在 PD 模型中激活 Akt 的作用。这些发现突显了 SFC 作为 PD 有前途的治疗候选物的潜力，值得进一步的临床研究。
