实验性自身免疫性脑脊髓炎
下调和上调
炎症
CD11c公司
硝基酪氨酸
免疫学
脑脊髓炎
小胶质细胞
一氧化氮
一氧化氮合酶
化学
药理学
医学
多发性硬化
内分泌学
生物化学
表型
基因
作者
Ahmed Nadeem,Sheikh F. Ahmad,Naif O. Al-Harbi,Wedad S. Sarawi,Sabry M. Attia,Wael A. Alanazi,Khalid E. Ibrahim,Sary Alsanea,Saleh A. Alqarni,Ali S. Alfardan,Saleh A. Bakheet
标识
DOI:10.1016/j.intimp.2022.108703
摘要
Multiple sclerosis (MS) is characterized by chronic autoimmune inflammation of central nervous system (CNS), i.e. brain and spinal cord. Autoimmune inflammation of the CNS and periphery causes demyelination of axons ultimately leading to clinical symptoms such as gait imbalance, lack of coordination and paraplegia. Innate immune cells such as dendritic cells and neutrophils play a critical role in the initiation and progression of MS through upregulation of oxidants. Two prominent pathways that play important role in regulation of oxidant-antioxidant balance are nuclear factor-erythroid factor 2-related factor 2(Nrf2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Nrf2-mediated upregulation of antioxidants counteracts NF-κB-mediated oxidant generation. Therefore, this study evaluated the effects of nutraceutical drug, acetyl-11-keto-β-boswellic acid (AKBA) in relapsing remitting model of experimental autoimmune encephelomyelitis (EAE). Efficacy of AKBA was explored on clinical symptoms, Nrf2, hemeoxygenase-1 (HO-1), NF-κB, inducible nitric oxide synthase (iNOS) in CNS and periphery of SJL/J mice. Our results show that expression of p-NF-κB and iNOS is elevated, whereas expression of Nrf2 and HO-1 is decreased in CD11c + DCs and CNS, which is linked with appearance of clinical symptoms in immunized SJL/J mice. Treatment of immunized SJL/J mice with AKBA causes improvement of clinical symptoms and downregulation of inflammatory markers in CD11c + DCs (p-NF-κB, iNOS, and nitrotyrosine), and CNS (p-NF-κB, iNOS, nitrotyrosine,lipid peroxides, and total antioxidant capacity). Treatment of immunized SJL/J mice with AKBA also causes rectification of Nrf2 signaling in CD11c + DCs, and CNS. These results propose AKBA ameliorates EAE disease progression through rectification of Nrf2 signaling and attenuation of NF-κB pathway in RR model of EAE. Therefore, nutraceutical compound, AKBA may be therapeutically useful in RRMS.
科研通智能强力驱动
Strongly Powered by AbleSci AI