Hematology and Transfusion Medicine Center, University of Campinas, Campinas, SP, Brazil.
Hematology and Transfusion Medicine Center, University of Campinas, Campinas, SP, Brazil.
Biomed Pharmacother. 2021 Nov;143:112211. doi: 10.1016/j.biopha.2021.112211. Epub 2021 Oct 5.
Lipopolysaccharide (LPS) is the major component of the outer membrane of Gram-negative bacteria and is usually administrated to establish models of inflammation. Artesunate (ART), a water-soluble artemisinin derivative, displays multiple pharmacological actions against tumors, viral infections, and inflammation, and has been used as a therapeutic weapon against malaria. In this study, our aim was to evaluate whether ART pretreatment is capable of preventing inflammation induced by LPS. BALB/c mice were treated with 100 mg/kg of ART i.p. for 7 days followed by a single dose of LPS. ART pretreatment led to an improvement in clinical score, prevented alterations in biochemical markers, and reestablished the platelet counts. Flow cytometry analysis showed that ART protected the inflammation mainly by reducing the percentage of M1 macrophages while increasing M2 macrophages and a reestablishment of classical monocytes in the BM. In the spleen, ART pretreatment increased N2 neutrophils, myeloid-derived suppressor cells (MDSC), and regulatory T cells, the latter was also increased in peripheral blood. In addition, a marked decrease in inflammatory cytokines and chemokines was observed in the ART treated group. Our data suggest that ART prevents inflammation, reducing tissue damage and restoring homeostasis.
脂多糖（LPS）是革兰氏阴性菌外膜的主要成分，通常用于建立炎症模型。青蒿琥酯（ART）是一种水溶性青蒿素衍生物，具有多种抗肿瘤、抗病毒感染和抗炎作用，已被用作治疗疟疾的治疗武器。在本研究中，我们旨在评估 ART 预处理是否能够预防 LPS 引起的炎症。BALB/c 小鼠腹腔注射 100mg/kg 的 ART7 天，然后单次给予 LPS。ART 预处理可改善临床评分，防止生化标志物改变，并恢复血小板计数。流式细胞术分析表明，ART 主要通过减少 M1 巨噬细胞的百分比，同时增加 M2 巨噬细胞和经典单核细胞在 BM 中的比例，来保护炎症。在脾脏中，ART 预处理增加了 N2 中性粒细胞、髓源性抑制细胞（MDSC）和调节性 T 细胞，外周血中也增加了调节性 T 细胞。此外，在 ART 治疗组中观察到炎症细胞因子和趋化因子明显减少。我们的数据表明，ART 可预防炎症，减少组织损伤并恢复内稳态。
