Molecular Neurobiology ( IF 4.6 ) Pub Date : 2021-08-02 , DOI: 10.1007/s12035-021-02497-5 Reza Nasrnezhad 1, 2 , Sohrab Halalkhor 2 , Farzin Sadeghi 3 , Fereshteh Pourabdolhossein 3, 4
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Inflammation, demyelination, glial activation, and oxidative damage are the most pathological hallmarks of multiple sclerosis (MS). Piperine, a main bioactive alkaloid of black pepper, possesses antioxidant, anti-inflammatory, and neuroprotective properties whose therapeutic potential has been less studied in the experimental autoimmune encephalomyelitis (EAE) models. In this study, the efficiency of piperine on progression of EAE model and myelin repair mechanisms was investigated. EAE was induced in female Lewis rats and piperine and its vehicle were daily administrated intraperitoneally from day 8 to 29 post immunization. We found that piperine alleviated neurological deficits and EAE disease progression. Luxol fast blue and H&E staining and immunostaining of lumbar spinal cord cross sections confirmed that piperine significantly reduced the extent of demyelination, inflammation, immune cell infiltration, microglia, and astrocyte activation. Gene expression analysis in lumbar spinal cord showed that piperine treatment decreased the level of pro-inflammatory cytokines (TNF-α, IL-1β) and iNOS and enhanced IL-10, Nrf2, HO-1, and MBP expressions. Piperine supplementation also enhanced the total antioxidant capacity (FRAP) and reduced the level of oxidative stress marker (MDA) in the CNS of EAE rats. Finally, we found that piperine has anti-apoptotic and neuroprotective effect in EAE through reducing caspase-3 (apoptosis marker) and enhancing BDNF and NeuN expressing cells. This study strongly indicates that piperine has a beneficial effect on the EAE progression and could be considered as a potential therapeutic target for MS treatment. Upcoming clinical trials will provide a deeper understanding of piperine’s role for the treatment of the MS.
Graphical abstract
中文翻译：
胡椒碱通过其神经保护、抗炎和抗氧化作用改善 Lewis 大鼠的实验性自身免疫性脑脊髓炎 (EAE)
炎症、脱髓鞘、神经胶质激活和氧化损伤是多发性硬化症 (MS) 的最病理标志。胡椒碱是黑胡椒的主要生物活性生物碱，具有抗氧化、抗炎和神经保护特性，其治疗潜力在实验性自身免疫性脑脊髓炎 (EAE) 模型中的研究较少。在这项研究中，研究了胡椒碱对 EAE 模型进展和髓鞘修复机制的效率。在雌性Lewis大鼠和胡椒碱中诱导EAE，并且从免疫后第8天到第29天每天腹膜内施用其载体。我们发现胡椒碱减轻了神经功能缺损和 EAE 疾病进展。Luxol 坚牢蓝和 H& 腰脊髓横断面的 E 染色和免疫染色证实胡椒碱显着降低了脱髓鞘、炎症、免疫细胞浸润、小胶质细胞和星形胶质细胞活化的程度。腰脊髓基因表达分析表明，胡椒碱治疗降低了促炎细胞因子（TNF-α、IL-1β）和 iNOS 的水平，并增强了 IL-10、Nrf2、HO-1 和 MBP 的表达。胡椒碱补充剂还增强了 EAE 大鼠中枢神经系统的总抗氧化能力 (FRAP) 并降低了氧化应激标志物 (MDA) 的水平。最后，我们发现胡椒碱通过减少 caspase-3（凋亡标志物）和增强 BDNF 和 NeuN 表达细胞在 EAE 中具有抗凋亡和神经保护作用。该研究强烈表明胡椒碱对 EAE 进展具有有益作用，可被视为 MS 治疗的潜在治疗靶点。即将进行的临床试验将使人们更深入地了解胡椒碱在治疗 MS 中的作用。
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