Kumar Nitish, Tyagi Nidhi, Mehan Sidharth, Singh Alok Pratap
SRM Modinagar College of Pharmacy, SRM Institute of Science and Technology (Deemed to be University), Delhi-NCR Campus, Modinagar, Ghaziabad, Uttar Pradesh, 201204, India.
Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga, Punjab, 142001, India.
CNS Neurol Disord Drug Targets. 2025;24(4):285-324. doi: 10.2174/0118715273336107241015100912.
Multiple sclerosis (MS) is a persistent autoimmune condition characterized by inflammation and neurodegeneration. The current efficacy of treatments is limited, which has generated interest in developing neuroprotective strategies. Solid lipid nanoparticles (SLNs) and probiotics are potential drug delivery vehicles for targeting the CNS (Central nervous system), regulating immune responses, and supporting neuroprotection in neurological conditions.
The study investigates how SLNs containing RSG (rosiglitazone) and probiotics can protect the nervous system in cases of MS. We administered toxin EtBr (Ethidium bromide) from day 1 to day 7, later followed by the treatment from day 8 to day 35. During this time interval, various behavioural parameters have been performed. Further, after 35th day, blood plasma of animals was collected to study complete CBC profiling and animals were sacrificed. Then, biochemical and molecular studies, gross morphology of brain sectioning, histopathological evaluation and estimation of fatty acid content in fecal matter were performed.
RSG shows neuroprotective effects by blocking the STAT-3 and mTOR signaling pathways and increasing the production of PPAR-gamma. GW9662, a PPAR-gamma antagonist given at a dose of 2 mg/kg (i.p), was utilized to evaluate the role of PPAR-gamma and to compare the efficacy of RSG and probiotic-loaded SLNs in potentially providing neuroprotection. The relationship between RSG and the STAT-3, mTOR, and PPAR-gamma pathways in MS was confirmed and validated using analysis. RSG and probiotic-loaded SLNs modulate the complete blood profiling of rats and improve the symptoms of MS. We assessed the diagnostic capabilities of different biological samples such as cerebrospinal fluid, blood plasma, and brain homogenates (specifically from the hippocampus, striatum, cortex, and midbrain) to analyze neurochemical changes linked to neurobehavioral changes in the progression of MS.
The study showed that combining RSG and probiotics in an experimental medication form improved symptoms of MS more effectively than using RSG alone. This improvement is likely due to changes in STAT-3, mTOR, and PPAR-gamma signaling pathways.
多发性硬化症（MS）是一种以炎症和神经退行性变为特征的持续性自身免疫性疾病。目前治疗的疗效有限，这引发了人们对开发神经保护策略的兴趣。固体脂质纳米粒（SLNs）和益生菌是用于靶向中枢神经系统（CNS）、调节免疫反应以及在神经疾病中支持神经保护的潜在药物递送载体。
该研究调查了含有罗格列酮（RSG）的固体脂质纳米粒和益生菌在MS病例中如何保护神经系统。从第1天到第7天给予毒素溴化乙锭（EtBr），随后从第8天到第35天进行治疗。在此时间间隔内，进行了各种行为参数测试。此外，在第35天后，采集动物血浆以研究全血细胞计数概况，并对动物实施安乐死。然后，进行生化和分子研究、脑切片大体形态学、组织病理学评估以及粪便中脂肪酸含量的测定。
RSG通过阻断信号转导和转录激活因子3（STAT - 3）和哺乳动物雷帕霉素靶蛋白（mTOR）信号通路并增加过氧化物酶体增殖物激活受体γ（PPAR - γ）的产生来发挥神经保护作用。以2 mg/kg（腹腔注射）剂量给予的PPAR - γ拮抗剂GW9662用于评估PPAR - γ的作用，并比较RSG和载益生菌固体脂质纳米粒在潜在提供神经保护方面的疗效。使用分析方法证实并验证了MS中RSG与STAT - 3、mTOR和PPAR - γ途径之间的关系。RSG和载益生菌固体脂质纳米粒调节大鼠的全血细胞概况并改善MS症状。我们评估了不同生物样品（如脑脊液、血浆和脑匀浆（特别是来自海马体、纹状体、皮质和中脑））的诊断能力，以分析与MS进展中神经行为变化相关的神经化学变化。
该研究表明，以实验药物形式将RSG和益生菌联合使用比单独使用RSG更有效地改善了MS症状。这种改善可能归因于STAT - 3、mTOR和PPAR - γ信号通路的变化。
