青蒿素及其衍生物在相关疾病中的免疫调节作用

青蒿素及其衍生物作为一线抗疟药物在世界上得到广泛应用。目前,用于临床的青蒿素衍生物包括双氢青蒿素、蒿甲醚、青蒿琥酯和蒿乙醚等。上海药物研究所在青蒿素基础上研发出了SM735、SM905、SM934等青蒿素衍生物,这些衍生物同样具有低毒、高生物利用度和潜在的免疫抑制效应等优点。近年来,越来越多的临床和实验研究表明青蒿素及其衍生物除具有良好的抗疟作用外,也具有明显的抗炎、抗肿瘤和免疫调节作用。青蒿素及其衍生物可通过抑制致病性T细胞的活化、抑制B细胞的活化和抗体的产生、增加调节性T细胞表达发挥免疫抑制作用,从而改善系统性红斑狼疮和类风湿性关节炎等自身免疫性疾病的症状。青蒿素及其衍生物还可通过调节哺乳动物免疫T细胞从而调节肿瘤免疫、诱导细胞凋亡等机制抑制肿瘤细胞生长,在乳腺癌和肺癌等多种癌症的治疗中发挥抗癌作用。与此同时,世界各地的研究人员仍在探索青蒿素衍生物的未知生物活性。在本综述中,我们对青蒿素及其衍生物的免疫调节机制及其在自身免疫性疾病中的作用和抑制肿瘤细胞的增殖、促进细胞凋亡、诱导细胞周期阻滞、干扰肿瘤浸润和转移、调节肿瘤信号通路等的最新进展进行了讨论,以期为青蒿素类药物的推广应用及研发提供参考。

Immunomodulative effects of artemisinin and its derivatives in the relative diseases

Artemisinin and its derivatives are widely used as first-line antimalarials in the world. Currently, artemisinin derivatives used in clinical treatment include dihydroartemisinin, artemether, artesunate and arteether, etc. Scientists from Shanghai Institute of Materia Medica (SIMM, CAS) designed a series of novel artemisinin derivatives such as SM735, SM905 and SM934, with lower toxicity, higher bioavailability, and potent immunosuppressive activity. In recent years, more and more clinical and trial evidences show that artemisinin and its derivatives have strong anti-inflammatory, anti-tumor and immunomodulative effects in addition to their prominent anti-malaria effect. Artemisinin and its derivatives play an immunosuppressive role by inhibiting the activation of pathogenic T cells, inhibiting the activation of B cells and the production of antibodies, and increasing the expression of regulatory T cells, thereby improving the symptoms of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Artemisinin and its derivatives can also regulate tumor immunity by regulating mammalian immune T cells, induce apoptosis and inhibit tumor cell growth, and play anticancer roles in the treatment of various cancers such as breast cancer and lung cancer. Meanwhile, researchers around the world are still exploring the unknown biological activity of artemisinin derivatives. In order to provide reference for the wider application and development of novel artemisinin drugs, we are discussing the latest progress in this review on the immunomodulatory mechanism of artemisinin and its derivatives and its role in autoimmune diseases, inhibiting the proliferation, promoting apoptosis of tumor cells, inducing cell cycle arrest, interfering with tumor invasion and metastasis, regulating tumor signaling pathways, etc.