Enhanced Neuroprotection in Experiment Multiple Sclerosis through Combined Rosiglitazone and Probiotic-Loaded Solid Lipid Nanoparticles: Modulation of Cellular Signaling Pathways.

Nitish Kumar, Nidhi Tyagi, Sidharth Mehan, Alok Pratap Singh
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Abstract

Background: 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.

Methods: 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.

Results: 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 in-silico 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.

Conclusion: 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.

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联合使用罗格列酮和益生菌载体固体脂质纳米颗粒增强实验性多发性硬化症的神经保护:细胞信号通路的调节。
背景:多发性硬化症(MS)是一种以炎症和神经变性为特征的顽固性自身免疫疾病。目前的治疗效果有限,这引起了人们对开发神经保护策略的兴趣。固体脂质纳米颗粒(SLNs)和益生菌是潜在的药物输送载体,可用于靶向中枢神经系统(CNS)、调节免疫反应和支持神经系统疾病的神经保护:本研究探讨了含有 RSG(罗格列酮)和益生菌的 SLNs 如何保护多发性硬化症患者的神经系统。我们从第1天到第7天施用毒素EtBr(溴化乙锭),随后从第8天到第35天进行治疗。在此期间,我们检测了各种行为参数。此外,在第 35 天后,收集动物血浆以研究完整的全血细胞计数,并将动物处死。然后,进行生化和分子研究、脑切片大体形态学研究、组织病理学评估和粪便中脂肪酸含量的估计:结果:RSG通过阻断STAT-3和mTOR信号通路以及增加PPAR-gamma的产生而显示出神经保护作用。GW9662是一种PPAR-γ拮抗剂,给药剂量为2毫克/千克(静脉注射),用于评估PPAR-γ的作用,并比较RSG和装载益生菌的SLNs在提供潜在神经保护方面的功效。通过使用in-silico分析,确认并验证了RSG与多发性硬化症中STAT-3、mTOR和PPAR-gamma通路之间的关系。RSG 和装载益生菌的 SLN 调节了大鼠的全血谱分析,改善了多发性硬化症的症状。我们评估了脑脊液、血浆和脑匀浆(特别是海马、纹状体、皮层和中脑)等不同生物样本的诊断能力,以分析多发性硬化症进展过程中与神经行为变化相关的神经化学变化:研究表明,与单独使用 RSG 相比,将 RSG 和益生菌以实验性药物形式结合使用能更有效地改善多发性硬化症的症状。这种改善可能是由于 STAT-3、mTOR 和 PPAR-gamma 信号通路发生了变化。
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