Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mithibai Campus, Vile Parle (W), V. M. Road, 400056, Mumbai, India.
Inflammopharmacology. 2021 Jun;29(3):617-640. doi: 10.1007/s10787-021-00813-y. Epub 2021 May 17.
Inflammation is not only a defense mechanism of the innate immune system against invaders, but it is also involved in the pathogenesis of many diseases such as atherosclerosis, thrombosis, diabetes, epilepsy, and many neurodegenerative disorders. The World Health Organization (WHO) reports worldwide estimates of people (9.6% in males and 18.0% in females) aged over 60 years, suffering from symptomatic osteoarthritis, and around 339 million suffering from asthma. Other chronic inflammatory diseases, such as ulcerative colitis and Crohn's disease are also highly prevalent. The existing anti-inflammatory agents, both non-steroidal and steroidal, are highly effective; however, their prolonged use is marred by the severity of associated side effects. A holistic approach to ensure patient compliance requires understanding the pathophysiology of inflammation and exploring new targets for drug development. In this regard, various intracellular cell signaling pathways and their signaling molecules have been identified to be associated with inflammation. Therefore, chemical inhibitors of these pathways may be potential candidates for novel anti-inflammatory drug approaches. This review focuses on the anti-inflammatory effect of these inhibitors (for JAK/STAT, MAPK, and mTOR pathways) describing their mechanism of action through literature search, current patents, and molecules under clinical trials.
炎症不仅是先天免疫系统抵御入侵者的防御机制,还参与了许多疾病的发病机制,如动脉粥样硬化、血栓形成、糖尿病、癫痫和许多神经退行性疾病。世界卫生组织(WHO)报告称,全球 60 岁以上人群中有症状性骨关节炎患者的估计人数(男性为 9.6%,女性为 18.0%),约有 3.39 亿人患有哮喘。其他慢性炎症性疾病,如溃疡性结肠炎和克罗恩病也很普遍。现有的抗炎药,包括非甾体类和甾体类,都非常有效;然而,由于其相关副作用的严重程度,长期使用这些药物受到了阻碍。为了确保患者的依从性,需要采用整体方法来了解炎症的病理生理学,并探索药物开发的新靶点。在这方面,已经确定了各种细胞内信号通路及其信号分子与炎症有关。因此,这些通路的化学抑制剂可能是新型抗炎药物方法的潜在候选药物。本综述重点介绍了这些抑制剂(针对 JAK/STAT、MAPK 和 mTOR 通路)的抗炎作用,通过文献检索、当前专利和临床试验中的分子描述了它们的作用机制。