The sesquiterpene lactone artemisinin from Artemisia annua L. is well established for malaria therapy, but its bioactivity spectrum is much broader. In this review, we give a comprehensive and timely overview of the literature regarding the immunosuppressive activity of artemisinin-type compounds toward inflammatory and autoimmune diseases. Numerous receptor-coupled signaling pathways are inhibited by artemisinins, including the receptors for interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), β3-integrin, or RANKL, toll-like receptors and growth factor receptors. Among the receptor-coupled signal transducers are extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), AKT serine/threonine kinase (AKT), mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK) kinase (MEK), phospholipase C γ1 (PLCγ), and others. All these receptors and signal transduction molecules are known to contribute to the inhibition of the transcription factor nuclear factor κ B (NF-κB). Artemisinins may inhibit NF-κB by silencing these upstream pathways and/or by direct binding to NF-κB. Numerous NF-κB-regulated downstream genes are downregulated by artemisinin and its derivatives, for example, cytokines, chemokines, and immune receptors, which regulate immune cell differentiation, apoptosis genes, proliferation-regulating genes, signal transducers, and genes involved in antioxidant stress response. In addition to the prominent role of NF-κB, other transcription factors are also inhibited by artemisinins (mammalian target of rapamycin [mTOR], activating protein 1 [AP1]/FBJ murine osteosarcoma viral oncogene homologue [FOS]/JUN oncogenic transcription factor [JUN]), hypoxia-induced factor 1α (HIF-1α), nuclear factor of activated T cells c1 (NF-ATC1), Signal transducers and activators of transcription (STAT), NF E2-related factor-2 (NRF-2), retinoic-acid-receptor-related orphan nuclear receptor γ (ROR-γt), and forkhead box P-3 (FOXP-3). Many in vivo experiments in disease-relevant animal models demonstrate therapeutic efficacy of artemisinin-type drugs against rheumatic diseases (rheumatoid arthritis, osteoarthritis, lupus erythematosus, arthrosis, and gout), lung diseases (asthma, acute lung injury, and pulmonary fibrosis), neurological diseases (autoimmune encephalitis, Alzheimer's disease, and myasthenia gravis), skin diseases (dermatitis, rosacea, and psoriasis), inflammatory bowel disease, and other inflammatory and autoimmune diseases. Randomized clinical trials should be conducted in the future to translate the plethora of preclinical results into clinical practice.

中文翻译：

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青蒿素类药物对炎症和自身免疫性疾病的免疫抑制活性

青蒿中的倍半萜内酯青蒿素L. 在疟疾治疗方面已广为人知，但其生物活性谱要广泛得多。在这篇综述中，我们对有关青蒿素类化合物对炎症和自身免疫性疾病的免疫抑制活性的文献进行了全面而及时的概述。青蒿素可抑制多种受体偶联信号通路，包括白细胞介素-1 (IL-1)、肿瘤坏死因子-α (TNF-α)、β3-整合素或 RANKL 受体、toll 样受体和生长因子受体. 受体偶联的信号转导剂包括细胞外信号调节蛋白激酶 (ERK)、c-Jun N-末端激酶 (JNK)、磷脂酰肌醇-4,5-二磷酸 3-激酶 (PI3K)、AKT 丝氨酸/苏氨酸激酶 (AKT) )、丝裂原活化蛋白激酶 (MAPK)/细胞外信号调节激酶 (ERK) 激酶 (MEK)、磷脂酶 C γ1 (PLCγ) 等。已知所有这些受体和信号转导分子都有助于抑制转录因子核因子 κ B (NF-κB)。青蒿素可以通过沉默这些上游通路和/或直接与 NF-κB 结合来抑制 NF-κB。许多 NF-κB 调节的下游基因被青蒿素及其衍生物下调，例如调节免疫细胞分化的细胞因子、趋化因子和免疫受体、凋亡基因、增殖调节基因、信号转导和参与抗氧化应激的基因回复。除了 NF-κB 的突出作用外，其他转录因子也被青蒿素（雷帕霉素的哺乳动物靶标 [mTOR]，激活蛋白 1 [AP1]/FBJ 鼠骨肉瘤病毒致癌基因同源物 [FOS]/JUN 致癌转录因子 [JUN]），缺氧诱导因子 1α（HIF-1α），活化 T 细胞核因子 c1（NF-ATC1），信号转导和转录激活因子 (STAT)、NF E2 相关因子 2 (NRF-2)、视黄酸受体相关孤核受体 γ (ROR-γt) 和叉头盒 P-3 (FOXP-3 ）。许多疾病相关动物模型的体内实验证明了青蒿素类药物对风湿性疾病（类风湿性关节炎、骨关节炎、红斑狼疮、关节病和痛风）、肺病（哮喘、急性肺损伤和肺纤维化）的治疗效果，神经系统疾病（自身免疫性脑炎、阿尔茨海默病和重症肌无力）、皮肤病（皮炎、酒渣鼻和牛皮癣），炎症性肠病，以及其他炎症和自身免疫性疾病。未来应进行随机临床试验，以将过多的临床前结果转化为临床实践。