Wankhede Mayuri, Rathod Ketan, Aswar Manoj, Aswar Urmila
Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Paud Road, Erandwane, Pune, Maharashtra, 411038, India.
Department of Pharmacology, Marathwada Mitra Mandal's College of Pharmacy, Thergaon, Pune, Maharashtra, 411033, India.
Neurochem Res. 2025 Sep 18;50(5):304. doi: 10.1007/s11064-025-04555-z.
Chronic treatment with levodopa often leads to levodopa-induced dyskinesia (LID), around 40% of individuals are affected. Stigmasterol exhibits antioxidant, anti-inflammatory, and glutamate-antagonist properties, acting through AKT-1, VEGFR, and IL-6 to prevent neuronal death. This study investigates the STI potential to mitigate LID. Male Sprague Dawley rats were assigned to five groups (SHAM, 6-OHDA, LID, STI 10, STI 20), with n = 10. PD was induced by stereotaxic infusion of 6-OHDA (3 µg/µL × 2.5 µL) into the right medial forebrain bundle. After a 21-day recovery period, development of PD was confirmed through behavioral assessment, including APO-induced rotation, footprint analyses, and a stepping test assessment conducted over 7 days. Subsequently, the rats were treated with levodopa + carbidopa and stigmasterol (10/20 mg/Kg) orally for 28 days. Abnormal involuntary movements (AIMs) were assessed at intervals of 1, 14, 21, and 28th days to evaluate the effect of stigmasterol on LID. On day 28, rats were euthanized, and brain samples were analyzed for biochemical, and histopathological changes in the striatum and substantia nigra using nissl staining. STI treatment (10/20 mg/Kg) significantly decreased AIMS, MDA level, TNF-α, IL-1β, NF- kB, and NLRP3 and significantly increased GSH, SOD, catalase and dopamine levels. The histopathology assessment restored neurons in the striatum and substantia nigra of the brain. The result concludes that co-administration of stigmasterol (10/20 mg/Kg) with L-DOPA + carbidopa restores DA level, showing anti-inflammatory, anti-oxidant properties, and neuroprotective activity. Stigmasterol can therefore be administered as an adjuvant treatment to delay LID.
长期使用左旋多巴治疗往往会导致左旋多巴诱导的运动障碍（LID），约40%的患者会受到影响。豆甾醇具有抗氧化、抗炎和谷氨酸拮抗剂特性，通过AKT-1、VEGFR和IL-6发挥作用以防止神经元死亡。本研究调查了豆甾醇减轻LID的潜力。将雄性Sprague Dawley大鼠分为五组（假手术组、6-OHDA组、LID组、豆甾醇10mg/kg组、豆甾醇20mg/kg组），每组n = 10。通过立体定向向右侧内侧前脑束注射6-OHDA（3µg/µL×2.5µL）诱导帕金森病。经过21天的恢复期后，通过行为评估确认帕金森病的发展，包括阿扑吗啡诱导的旋转、足迹分析以及为期7天的步测评估。随后，大鼠口服左旋多巴+卡比多巴和豆甾醇（10/20mg/kg），持续28天。每隔1、14、21和28天评估异常不自主运动（AIMs），以评估豆甾醇对LID的影响。在第28天，对大鼠实施安乐死，并使用尼氏染色分析脑样本中纹状体和黑质的生化及组织病理学变化。豆甾醇治疗（10/20mg/kg）显著降低了AIMs、丙二醛水平、肿瘤坏死因子-α、白细胞介素-1β、核因子-κB和NLRP3，并显著提高了谷胱甘肽、超氧化物歧化酶、过氧化氢酶和多巴胺水平。组织病理学评估恢复了脑内纹状体和黑质中的神经元。结果表明，豆甾醇（10/20mg/kg）与左旋多巴+卡比多巴联合使用可恢复多巴胺水平，具有抗炎、抗氧化特性及神经保护活性。因此，豆甾醇可作为辅助治疗药物来延缓LID。
