Alshahrani Sultan M, Al-Kuraishy Hayder M, Al-Gareeb Ali I, Albuhadily Ali K, Fawzy Mohamed N, Kadasah Sultan F, Alruwaili Mubarak, Papadakis Marios, Alexiou Athanasios, El-Saber Batiha Gaber
College of Pharmacy, King Khalid University, Abha, 61441, Saudi Arabia; King Salman Center for Disability Research, Riyadh, 11614, Saudi Arabia.
Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq.
Neuropharmacology. 2025 Nov 1;278:110555. doi: 10.1016/j.neuropharm.2025.110555. Epub 2025 Jun 6.
Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). α-Synuclein (α-Syn) is a key protein implicated in PD pathogenesis, with its structural and biophysical properties widely investigated due to their role in disease mechanisms. The presence of Lewy bodies and Lewy neurites, pathological hallmarks of PD primarily composed of aggregated α-Syn, further underscores its critical involvement. This correlation has led to the hypothesis that α-Syn aggregation actively contributes to PD development. Recent studies have implicated oligomers formed during the initial phases of protein aggregation as the primary neurotoxic agents driving cellular degeneration in PD. This pathological process worsens mitochondrial dysfunction, oxidative stress, and microglial activation, ultimately contributing to SNpc degeneration and PD progression. Currently, available PD medications only provide symptomatic relief and do not address underlying neuropathological mechanisms such as oxidative stress, mitochondrial impairment, α-syn aggregation, or SNpc degeneration. Moreover, long-term use of anti-PD drugs like L-DOPA can lead to motor complications and systemic side effects. As a result, repurposing traditional herbal medicines with antioxidant and anti-inflammatory properties presents a promising therapeutic approach. Studies suggest that berberine (BBR) may mitigate PD-related neuropathology. However, the exact mechanisms by which BBR exerts its neuroprotective effects remain unclear. This review explores the potential molecular pathways through which BBR could alleviate PD pathology.
帕金森病（PD）是一种慢性神经退行性疾病，其特征是黑质致密部（SNpc）中多巴胺能神经元进行性退化。α-突触核蛋白（α-Syn）是一种与PD发病机制相关的关键蛋白，由于其在疾病机制中的作用，其结构和生物物理特性得到了广泛研究。路易小体和路易神经突的存在是PD的病理标志，主要由聚集的α-Syn组成，这进一步强调了其关键作用。这种相关性导致了一种假说，即α-Syn聚集积极促进PD的发展。最近的研究表明，在蛋白质聚集初始阶段形成的寡聚体是驱动PD细胞退化的主要神经毒性因子。这种病理过程会加剧线粒体功能障碍、氧化应激和小胶质细胞活化，最终导致SNpc退化和PD进展。目前，现有的PD药物只能提供症状缓解，无法解决潜在的神经病理机制，如氧化应激、线粒体损伤、α-突触核蛋白聚集或SNpc退化。此外，长期使用左旋多巴等抗PD药物会导致运动并发症和全身副作用。因此，将具有抗氧化和抗炎特性的传统草药重新用于治疗是一种很有前景的治疗方法。研究表明，黄连素（BBR）可能减轻与PD相关的神经病理学。然而，BBR发挥神经保护作用的确切机制仍不清楚。本综述探讨了BBR减轻PD病理的潜在分子途径。
