Pandey Shivam Kumar, Nanda Anjuman, Gautam Avtar Singh, Singh Rakesh Kumar
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER) - Raebareli. Transit campus, Bijnour-sisendi road, Sarojini nagar, Lucknow, 226002, Uttar Pradesh, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER) - Raebareli. Transit campus, Bijnour-sisendi road, Sarojini nagar, Lucknow, 226002, Uttar Pradesh, India.
Free Radic Biol Med. 2025 Jun;233:340-354. doi: 10.1016/j.freeradbiomed.2025.04.013. Epub 2025 Apr 7.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective degeneration of dopaminergic neurons in the substantia nigra, leading to profound motor dysfunction and non-motor symptoms.
Despite significant advancements in understanding PD pathophysiology, effective disease-modifying therapies remain elusive. Current research efforts are increasingly focused on developing and refining advanced in-vivo models to unravel PD mechanisms and explore novel therapeutic interventions. In this study, we investigated the neuroprotective potential of Betulinic acid (BA), a natural triterpenoid, in an experimental model of PD.
We evaluated the amelioration of motor impairments and associated pathological alterations in Wistar rats. The experimental model involved the administration of lipopolysaccharide (LPS) and ferrous sulfate (FeSO). BA was administered orally to evaluate its potential neuroprotective effects.
Our findings demonstrated that BA administration significantly reversed behavioral deficits and mitigated molecular, immunohistopathological, and biochemical abnormalities in LPS + FeSO-induced PD model. Notably, BA treatment restored levels of tyrosine hydroxylase (TH) and reduced alpha-synuclein (α-syn) accumulation, both of which were significantly altered in this model. These neuroprotective effects were accompanied by a reduction in oxidative stress, ferroptosis, and apoptosis biomarkers implicated in neurodegeneration.
These results collectively suggested that α-syn aggregation, ferroptosis, and apoptotic cell death are the critical contributors to PD pathology and highlighted Betulinic acid as a promising therapeutic candidate for combating neurodegeneration in PD. These findings may open new avenues for developing pharmacological agents targeting the complex mechanisms of PD.
帕金森病（PD）是一种进行性神经退行性疾病，其特征是黑质中多巴胺能神经元的选择性退化，导致严重的运动功能障碍和非运动症状。
尽管在理解PD病理生理学方面取得了重大进展，但有效的疾病修饰疗法仍然难以捉摸。目前的研究工作越来越集中在开发和完善先进的体内模型，以揭示PD机制并探索新的治疗干预措施。在本研究中，我们研究了天然三萜类化合物桦木酸（BA）在PD实验模型中的神经保护潜力。
我们评估了Wistar大鼠运动障碍的改善情况以及相关的病理改变。实验模型包括给予脂多糖（LPS）和硫酸亚铁（FeSO）。口服BA以评估其潜在的神经保护作用。
我们的研究结果表明，在LPS + FeSO诱导的PD模型中，给予BA可显著逆转行为缺陷，并减轻分子、免疫组织病理学和生化异常。值得注意的是，BA治疗恢复了酪氨酸羟化酶（TH）的水平，并减少了α-突触核蛋白（α-syn）的积累，这两者在该模型中均有显著改变。这些神经保护作用伴随着神经退行性变相关的氧化应激、铁死亡和凋亡生物标志物的减少。
这些结果共同表明，α-syn聚集、铁死亡和凋亡细胞死亡是PD病理的关键因素，并突出了桦木酸作为对抗PD神经退行性变的有前途的治疗候选物。这些发现可能为开发针对PD复杂机制的药物开辟新途径。
