Jacob Haritha, Curtis Annie M, Kearney Cathal J
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and Trinity College Dublin, Dublin, Ireland.
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and Trinity College Dublin, Dublin, Ireland; School of Pharmacy and Biomolecular Sciences, RCSI, Dublin, Ireland.
Biochem Pharmacol. 2020 Dec;182:114254. doi: 10.1016/j.bcp.2020.114254. Epub 2020 Oct 1.
The circadian clock is a collection of endogenous oscillators with a periodicity of ~ 24 h. Recently, our understanding of circadian rhythms and their regulation at genomic and physiologic scales has grown significantly. Knowledge of the circadian influence on biological processes has provided new possibilities for novel pharmacological strategies. Directly targeting the biological clock or its downstream targets, and/or using timing as a variable in drug therapy are now important pharmacological considerations. The circadian machinery mediates many aspects of the inflammatory response and, reciprocally, an inflammatory environment can disrupt circadian rhythms. Therefore, intense interest exists in leveraging circadian biology as a means to treat chronic inflammatory diseases such as sepsis, asthma, rheumatoid arthritis, osteoarthritis, and cardiovascular disease, which all display some type of circadian signature. The purpose of this review is to evaluate the crosstalk between circadian rhythms, inflammatory diseases, and their pharmacological treatment. Evidence suggests that carefully rationalized application of chronotherapy strategies - alone or in combination with small molecule modulators of circadian clock components - can improve efficacy and reduce toxicity, thus warranting further investigation and use.
生物钟是一组周期约为24小时的内源性振荡器。最近，我们对昼夜节律及其在基因组和生理水平上的调节的理解有了显著增长。昼夜节律对生物过程影响的知识为新型药理学策略提供了新的可能性。直接靶向生物钟或其下游靶点，和/或在药物治疗中把时间作为一个变量，现在是重要的药理学考量因素。生物钟机制介导炎症反应的许多方面，反之，炎症环境也会扰乱昼夜节律。因此，人们对利用昼夜节律生物学来治疗慢性炎症性疾病，如脓毒症、哮喘、类风湿性关节炎、骨关节炎和心血管疾病，有着浓厚的兴趣，这些疾病都表现出某种类型的昼夜节律特征。本综述的目的是评估昼夜节律、炎症性疾病及其药物治疗之间的相互作用。有证据表明，精心合理应用时间治疗策略——单独应用或与生物钟组件的小分子调节剂联合应用——可以提高疗效并降低毒性，因此值得进一步研究和应用。
