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Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets
Pharmacology & Therapeutics ( IF 13.5 ) Pub Date : 2017-08-23 , DOI: 10.1016/j.pharmthera.2017.08.011
Vikas Mishra , Jaspreet Banga , Patricia Silveyra

Asthma is a complex inflammatory disease characterized by airway inflammation and hyperresponsiveness. The mechanisms associated with the development and progression of asthma have been widely studied in multiple populations and animal models, and these have revealed involvement of various cell types and activation of intracellular signaling pathways that result in activation of inflammatory genes. Significant contributions of Toll-like-receptors (TLRs) and transcription factors such as NF-кB, have been reported as major contributors to inflammatory pathways. These have also recently been associated with mechanisms of oxidative biology. This is of important clinical significance as the observed inefficacy of current available treatments for severe asthma is widely attributed to oxidative stress. Therefore, targeting oxidizing molecules in conjunction with inflammatory mediators and transcription factors may present a novel therapeutic strategy for asthma. In this review, we summarize TLRs and NF-кB pathways in the context of exacerbation of asthma pathogenesis and oxidative biology, and we discuss the potential use of polyphenolic flavonoid compounds, known to target these pathways and possess antioxidant activity, as potential therapeutic agents for asthma.



中文翻译:

哮喘和炎症的氧化应激和细胞途径:治疗策略和药理学目标

哮喘是一种复杂的炎症性疾病,其特征在于气道炎症和反应过度。与哮喘的发生和发展有关的机制已在多个种群和动物模型中进行了广泛研究,这些机制揭示了多种细胞类型的参与和导致炎症基因激活的细胞内信号传导途径的激活。据报道,Toll样受体(TLR)和转录因子(例如NF-кB)的显着贡献是炎症途径的主要贡献者。这些最近也与氧化生物学机制有关。这具有重要的临床意义,因为目前观察到的对严重哮喘的无效治疗被广泛归因于氧化应激。所以,靶向氧化分子与炎症介质和转录因子的结合可能会提出一种新的哮喘治疗策略。在这篇综述中,我们在哮喘发病机理和氧化生物学加剧的背景下总结了TLRs和NF-кB途径,并讨论了靶向这些途径并具有抗氧化活性的多酚类黄酮化合物作为潜在治疗剂的潜在用途。哮喘。

更新日期:2017-08-23
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