Xanthium Alleviates LPS-induced Inflammation by Inhibition of JAK/STAT, NF-κB, and MAPK Pathways in Macrophages

Xanthium (Xa) is one of the active ingredients of Xanthium strumarium L. . Here, we focused on exploring the inhibitory effect of Xanthium on inflammation and the potential anti-inflammatory pathways. After LPS-stimulation of the cells, the generation of NO and associated pro-inflammatory factors (TNF-α, IL-1β and IL-6) increased, whereas both were reduced after pretreatment with Xanthium. However, IL-10, an anti-inflammatory factor, was increased by LPS stimulation, which was reduced by Xanthium pretreatment. Furthermore, when compared to LPS-stimulated cells alone, the mRNA expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2), as well as TNF-α, IL-1β and IL-6, was considerably downregulated and suppressed after pretreatment with Xanthium. In addition, Xanthium showed inhibitory effects on iNOS and COX2 at the protein level. Xanthium inhibits both the STAT3 and NF-κB signaling pathways. Xanthium suppresses the inflammatory reaction generated by LPS and exerts anti-inflammatory effects mainly through JAK/STAT, NF-κB and MAPK pathways, among others. Therefore, Xanthium could be a good anti-inflammatory medication candidate.

苍耳素（Xanthium，简称Xa）是苍耳（Xanthium strumarium L.）的活性成分之一。本研究旨在探究苍耳素对炎症的抑制作用及其潜在的抗炎通路。经脂多糖（Lipopolysaccharide，LPS）刺激细胞后，一氧化氮（nitric oxide，NO）及相关促炎细胞因子（肿瘤坏死因子-α（Tumor Necrosis Factor-α，TNF-α）、白细胞介素-1β（Interleukin-1β，IL-1β）、白细胞介素-6（Interleukin-6，IL-6））的生成量显著升高；而经苍耳素预处理后，上述指标均有所降低。但经脂多糖刺激后，抗炎因子白细胞介素-10（Interleukin-10，IL-10）的表达量升高，而苍耳素预处理可逆转该变化并降低其表达水平。此外，与单独经脂多糖刺激的细胞相比，苍耳素预处理可显著下调诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）、环氧合酶-2（cyclooxygenase-2，COX2）以及肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6的mRNA表达水平。同时，苍耳素在蛋白层面同样对iNOS与COX2具有抑制作用。苍耳素可同时抑制信号转导与转录激活因子3（Signal Transducer and Activator of Transcription 3，STAT3）与核因子-κB（Nuclear Factor-kappa B，NF-κB）信号通路。苍耳素可抑制脂多糖诱导的炎症反应，其抗炎作用主要通过Janus激酶/信号转导与转录激活因子（JAK/STAT）、核因子-κB（NF-κB）以及丝裂原活化蛋白激酶（Mitogen-Activated Protein Kinase，MAPK）等通路实现。因此，苍耳素有望成为优质的抗炎候选药物。