Prajapati Pradyuman, Singh Pankaj, Doshi Gaurav
Department of Pharmacology, Toxicology and Therapeutics, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V.M. Road, Vile Parle (W), Mumbai, India.
Curr Drug Targets. 2025;26(8):507-533. doi: 10.2174/0113894501372670250408074908.
Rheumatoid arthritis is a chronic autoimmune condition marked by persistent inflammation and joint deterioration, affecting millions of people worldwide. The objective of many of the drugs being prescribed for treating RA patients is to reduce inflammation and halt the progression of the disease. Additionally, several of these therapeutic options have disadvantages, namely the potential for illness recurrence and unfavorable side effects with prolonged usage. Due to these inefficiencies, treating RA now requires an entirely novel approach. In recent times, there has been a shift in emphasis towards directly targeting transcription factors (TFs) due to their crucial involvement in the progression of RA, triggering essential pro-inflammatory adhesion molecules, enzymes, chemokines, and cytokines. Considering this, researchers are investigating synthetic and natural compounds as potential options to target essential TFs and associated signaling pathways. This review focuses on the potential natural compounds and synthetic drugs to target four significant TFs, namely, hypoxia-inducible factor 1α, nuclear factor erythroid 2-related factor 2, retinoic acid-related orphan receptor gamma t, and signal transducer and activator and transcription, highlighting their contributions to revolutionizing RA treatment, thus aiming for more effective and safer therapeutic options. This review also offers an overview of the current status of various natural compounds and synthetic drugs under consideration for targeting the signaling pathways that trigger the activation of TFs.
类风湿性关节炎是一种慢性自身免疫性疾病，其特征是持续炎症和关节退化，影响着全球数百万人。为类风湿性关节炎患者开的许多药物的目标是减轻炎症并阻止疾病进展。此外，这些治疗选择中有几种存在缺点，即疾病复发的可能性以及长期使用时的不良副作用。由于这些低效性，现在治疗类风湿性关节炎需要一种全新的方法。近年来，由于转录因子（TFs）在类风湿性关节炎进展中起关键作用，触发重要的促炎粘附分子、酶、趋化因子和细胞因子，因此重点已转向直接靶向转录因子。考虑到这一点，研究人员正在研究合成和天然化合物作为靶向关键转录因子和相关信号通路的潜在选择。本综述重点关注靶向四种重要转录因子，即缺氧诱导因子1α、核因子红细胞2相关因子2、视黄酸相关孤儿受体γt以及信号转导和激活因子与转录因子的潜在天然化合物和合成药物，强调它们对革新类风湿性关节炎治疗的贡献，从而寻求更有效和更安全的治疗选择。本综述还概述了正在考虑用于靶向触发转录因子激活的信号通路的各种天然化合物和合成药物的现状。
