Oleacein Attenuates the Pathogenesis of Experimental Autoimmune Encephalomyelitis through Both Antioxidant and Anti-Inflammatory Effects.
Oleacein Attenuates the Pathogenesis of Experimental Autoimmune Encephalomyelitis through Both Antioxidant and Anti-Inflammatory Effects.
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DOI：
10.3390/antiox9111161
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发表时间：
2020-11-21
期刊：
影响因子：
--
通讯作者：
Nieto ML
中科院分区：
文献类型：
--
作者：
Gutiérrez-Miranda B;Gallardo I;Melliou E;Cabero I;Álvarez Y;Magiatis P;Hernández M;Nieto ML
氧化应激和促炎细胞因子是影响多发性硬化症（MS）疾病进展的因素。油酸素 (OLE) 是一种橄榄环烯醚萜苷，具有强大的抗氧化和抗炎活性，这表明其在治疗神经炎症性疾病方面具有潜在的应用前景。在此，我们研究了 OLE 对实验性自身免疫性脑脊髓炎 (EAE)（一种多发性硬化症动物模型）主要临床病理特征的影响，包括瘫痪、脱髓鞘、中枢神经系统 (CNS) 炎症/氧化应激和血脑屏障 (BBB) 破坏。方法：用髓鞘少突胶质细胞糖蛋白肽MOG35-55免疫小鼠诱导EAE，并从免疫当天开始给予OLE。收集血清、视神经、脊髓和小脑，以评估全身水平以及中枢神经系统内的免疫调节活性。此外，BV2 小胶质细胞和视网膜神经节细胞系 RGC-5 用于确认 OLE 对 CNS 驻留细胞的直接影响。结果：我们表明 OLE 治疗有效降低了 EAE 典型的临床评分和组织学体征。组织学评估证实，与未治疗的小鼠相比，经 OLE 治疗的 EAE 小鼠中枢神经系统组织中的白细胞浸润、脱髓鞘、血脑屏障破坏和超氧阴离子积累均有所减少。 OLE 显着降低促炎细胞因子（IL-13、TNFα、GM-CSF、MCP-1 和 IL-1β）的表达，同时增加抗炎细胞因子 IL-10。 OLE治疗的EAE小鼠中抗MOG35-55抗体的血清水平也较低。此外，OLE 显着减少了氧化系统参数的存在，同时上调了 ROS 干扰物 Sestrin-3。从机制上讲，OLE 可以阻止 BV2 细胞中 NLRP3 的表达、p65-NF-κB 的磷酸化，并减少相关炎症刺激诱导的促炎介质的合成。 OLE 不影响 BV2 小胶质细胞的活力或吞噬能力。此外，OLE 还可以阻止氧化应激诱导的 RGC-5 凋亡。结论：总而言之，我们的结果表明，抗氧化和抗炎 OLE 对 EAE 小鼠的中枢神经系统具有神经保护作用，指出这种天然产物可以作为多发性硬化症治疗研究的候选药物。
Oxidative stress and proinflammatory cytokines are factors affecting multiple sclerosis (MS) disease progression. Oleacein (OLE), an olive secoiridoid, possesses powerful antioxidant and anti-inflammatory activities, which suggests its potential application to treat neuroinflammatory disorders. Herein, we investigated the impact of OLE on the main clinic-pathological features of experimental autoimmune encephalomyelitis (EAE), an animal model for MS, including paralysis, demyelination, central nervous system (CNS) inflammation/oxidative stress and blood-brain barrier (BBB) breakdown. Methods: Mice were immunized with the myelin oligodendrocyte glycoprotein peptide, MOG35-55, to induce EAE, and OLE was administrated from immunization day. Serum, optic nerve, spinal cord and cerebellum were collected to evaluate immunomodulatory activities at a systemic level, as well as within the CNS. Additionally, BV2 microglia and the retinal ganglion cell line RGC-5 were used to confirm the direct effect of OLE on CNS-resident cells. Results: We show that OLE treatment effectively reduced clinical score and histological signs typical of EAE. Histological evaluation confirmed a decrease in leukocyte infiltration, demyelination, BBB disruption and superoxide anion accumulation in CNS tissues of OLE-treated EAE mice compared to untreated ones. OLE significantly decreased expression of proinflammatory cytokines (IL-13, TNFα, GM-CSF, MCP-1 and IL-1β), while it increased the anti-inflammatory cytokine IL-10. Serum levels of anti-MOG35-55 antibodies were also lower in OLE-treated EAE mice. Further, OLE significantly diminished the presence of oxidative system parameters, while upregulated the ROS disruptor, Sestrin-3. Mechanistically, OLE prevented NLRP3 expression, phosphorylation of p65-NF-κB and reduced the synthesis of proinflammatory mediators induced by relevant inflammatory stimuli in BV2 cells. OLE did not affect viability or the phagocytic capabilities of BV2 microglia. In addition, apoptosis of RGC-5 induced by oxidative stressors was also prevented by OLE. Conclusion: Altogether, our results show that the antioxidant and anti-inflammatory OLE has neuroprotective effects in the CNS of EAE mice, pointing out this natural product as a candidate to consider for research on MS treatments.
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影响因子：
4.6
作者：
Diamantakos, Panagiotis;Giannara, Triada;Magiatis, Prokopios
通讯作者：
Magiatis, Prokopios
DOI：
10.1016/b978-0-444-63916-5.00015-x
发表时间：
2018-01-01
期刊：
BALANCE, GAIT, AND FALLS
影响因子：
--
作者：
Cameron, Michelle H.;Nilsagard, Ylva
通讯作者：
Nilsagard, Ylva
影响因子：
6.4
作者：
Gray, Elizabeth;Thomas, Taya L.;Love, Seth
通讯作者：
Love, Seth
DOI：
10.1016/j.pathophys.2010.04.004
发表时间：
2011-02
期刊：
Pathophysiology : the official journal of the International Society for Pathophysiology
影响因子：
--
作者：
Denic A;Johnson AJ;Bieber AJ;Warrington AE;Rodriguez M;Pirko I
通讯作者：
Pirko I
影响因子：
11.2
作者：
Kopnin, Pavel B.;Agapova, Larissa S.;Chumakov, Peter M.
通讯作者：
Chumakov, Peter M.