Department of Physical Medicine and Rehabilitation, The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou, China.
Department of Rheumatology, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, China.
Front Immunol. 2024 Oct 25;15:1432625. doi: 10.3389/fimmu.2024.1432625. eCollection 2024.
Artemisinin and its derivatives are widely recognized as first-line treatments for malaria worldwide. Recent studies have demonstrated that artemisinin-based antimalarial drugs, such as artesunate, dihydroartemisinin, and artemether, not only possess excellent antimalarial properties but also exhibit antitumor, antifungal, and immunomodulatory effects. Researchers globally have synthesized artemisinin derivatives like SM735, SM905, and SM934, which offer advantages such as low toxicity, high bioavailability, and potential immunosuppressive properties. These compounds induce immunosuppression by inhibiting the activation of pathogenic T cells, suppressing B cell activation and antibody production, and enhancing the differentiation of regulatory T cells. This review summarized the mechanisms by which artemisinin and its analogs modulate excessive inflammation and immune responses in rheumatic and skeletal diseases, autoimmune inflammatory diseases, and autoimmune disorders, through pathways including TNF, Toll-like receptors, IL-6, RANKL, MAPK, PI3K/AKT/mTOR, JAK/STAT, and NRF2/GPX4. Notably, in the context of the NF-κB pathway, artemisinin not only inhibits NF-κB expression by disrupting upstream cascades and/or directly binding to NF-κB but also downregulates multiple downstream genes controlled by NF-κB, including inflammatory chemokines and their receptors. These downstream targets regulate various immune cell functions, apoptosis, proliferation, signal transduction, and antioxidant responses, ultimately intervening in systemic autoimmune diseases and autoimmune responses in organs such as the kidneys, nervous system, skin, liver, and biliary system by modulating immune dysregulation and inflammatory responses. Ongoing multicenter randomized clinical trials are investigating the effects of these compounds on rheumatic, inflammatory, and autoimmune diseases, with the aim of translating promising preclinical data into clinical applications.
青蒿素及其衍生物被广泛认为是全球治疗疟疾的一线药物。最近的研究表明，青蒿素类抗疟药物，如青蒿琥酯、双氢青蒿素和蒿甲醚，不仅具有优异的抗疟作用，而且具有抗肿瘤、抗真菌和免疫调节作用。全球研究人员合成了青蒿素衍生物，如 SM735、SM905 和 SM934，它们具有低毒性、高生物利用度和潜在的免疫抑制特性等优点。这些化合物通过抑制致病 T 细胞的激活、抑制 B 细胞的激活和抗体产生以及增强调节性 T 细胞的分化来诱导免疫抑制。本综述总结了青蒿素及其类似物通过 TNF、Toll 样受体、IL-6、RANKL、MAPK、PI3K/AKT/mTOR、JAK/STAT 和 NRF2/GPX4 等途径调节风湿和骨骼疾病、自身免疫性炎症性疾病和自身免疫性疾病中过度炎症和免疫反应的机制。值得注意的是，在 NF-κB 途径中，青蒿素不仅通过破坏上游级联反应和/或直接与 NF-κB 结合来抑制 NF-κB 的表达，而且还下调 NF-κB 控制的多个下游基因，包括炎症趋化因子及其受体。这些下游靶标调节各种免疫细胞功能、细胞凋亡、增殖、信号转导和抗氧化反应，最终通过调节免疫失调和炎症反应来干预系统性自身免疫性疾病和肾脏、神经系统、皮肤、肝脏和胆道系统等器官的自身免疫反应。正在进行的多中心随机临床试验正在研究这些化合物对风湿、炎症和自身免疫性疾病的影响，旨在将有前途的临床前数据转化为临床应用。
