Nikolova-Ganeva Kalina A, Mihaylova Nikolina M, Kechidzhieva Lidiya A, Ivanova Kristina I, Zarkov Alexander S, Parzhanov Daniel L, Ivanov Momchil M, Marchev Andrey S
Department of Immunology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.
Laboratory of Eukaryotic Cell Biology, Department of Biotechnology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, Bulgaria.
Int J Mol Sci. 2025 Jul 16;26(14):6813. doi: 10.3390/ijms26146813.
Rheumatoid arthritis (RA) is a progressive and systemic autoimmune disease, characterized by a chronic inflammatory process, affecting the lining of the synovial joints, many body organs/systems, and blood vessels. Its pathological hallmarks are hyperplasic synovium, bone erosion, and progressive joint destruction. Rheumatoid arthritis affects over 20 million people, with a worldwide prevalence of 0.5-1.0%, exhibiting gender, ethnic, and geographical differences. The progressive disability severely impairs physical motion and quality of life and is finally leading to a shortened life span. The pathogenesis of RA is a complex and still poorly understood process in which genetic and environmental factors are principally associated. Current treatment mostly relies on conventional/non-biological disease-modifying anti-rheumatic drugs (cDMARDs), analgesics, non-steroidal anti-inflammatory drugs, glucocorticoids, steroids, immunosuppresants, and biologic DMARDs, which only control inflammation and pain. Along with side effects (drug toxicity and intolerance), these anti-rheumatic drugs possess limited efficacy. Therefore, the discovery of novel multi-target therapeutics with an improved safety profile that function as inhibitors of RA-linked signaling systems are in high demand, and this is in the interest of both patients and clinicians. Plant-derived extracts, nutritional supplements, dietary medicine, and molecules with anti-inflammatory activity represent promising adjuvant agents or alternatives for RA therapeutics. This review not only aims to discuss the basic features of RA pathogenesis, risk factors, and signaling pathways but also highlights the research progress in pre-clinical RA in in vitro and in vivo models, revealing new avenues in the management of the disease in terms of comprehensive multidisciplinary strategies originating from medicinal plants and plant-derived molecules.
类风湿关节炎（RA）是一种进行性全身性自身免疫性疾病，其特征为慢性炎症过程，会影响滑膜关节的内膜、许多身体器官/系统以及血管。其病理特征为滑膜增生、骨侵蚀和进行性关节破坏。类风湿关节炎影响着超过2000万人，全球患病率为0.5 - 1.0%，存在性别、种族和地域差异。这种进行性残疾严重损害身体活动能力和生活质量，最终导致寿命缩短。RA的发病机制是一个复杂且仍未被充分理解的过程，主要与遗传和环境因素相关。目前的治疗主要依赖于传统/非生物改善病情抗风湿药物（cDMARDs）、镇痛药、非甾体抗炎药、糖皮质激素、类固醇、免疫抑制剂和生物DMARDs，这些药物仅能控制炎症和疼痛。除了副作用（药物毒性和不耐受）外，这些抗风湿药物的疗效有限。因此，迫切需要发现具有改善安全性的新型多靶点治疗药物，作为RA相关信号系统的抑制剂，这对患者和临床医生都有利。植物提取物、营养补充剂、饮食疗法以及具有抗炎活性的分子是RA治疗有前景的辅助药物或替代药物。本综述不仅旨在讨论RA发病机制、危险因素和信号通路的基本特征，还强调了在体外和体内模型中RA临床前研究的进展，从源自药用植物和植物衍生分子的综合多学科策略方面揭示了该疾病管理的新途径。
