Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon, Korea.
Department of Medical Science, College of Medicine, Chungnam National University, Daejeon, Korea.
PLoS One. 2018 Nov 19;13(11):e0207696. doi: 10.1371/journal.pone.0207696. eCollection 2018.
Stellaria dichotoma var. lanceolata (SdLv), a member of the Caryophyllaceae, is a traditional herbal medicine that has been used to treat fever, night sweats, and malaria in East Asia. Inflammation plays an essential role in both host defense and pathogenesis during infection by diverse intracellular pathogens. Herein, we showed that an herbal extract from SdLv effectively attenuated inflammatory responses from infection of Mycobacterium abscessus (Mab), but not Toxoplasma gondii (T. gondii). In primary murine macrophages, Mab infection resulted in the rapid activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK), as well as in the generation of proinflammatory cytokines, such as tumor necrosis factor α and interleukin-6, which were all significantly inhibited by pretreatment with SdLv. However, herbal extracts from Bupleurum chinense DC. (Buch) or Bupleurum falcatum L. (Bufa) did not affect M. abs-induced activation of proinflammatory responses. Importantly, we demonstrated that generation of intracellular reactive oxygen species, which are important signaling intermediaries in the activation of NF-κB and the MAPK signaling pathway, was rapidly increased in Mab-infected macrophages, and this was effectively suppressed by pretreatment with SdLv, but not Buch and Bufa. We further found that the treatment of Buch and Bufa, but not SdLv, led to the activation of NF-κB and the MAPK signaling pathway and the generation of intracellular reactive oxygen species. Moreover, oral administration of SdLv significantly reduced lethality in Mab-infected mice. Collectively, these results suggest the possible use of SdLv as an effective treatment for Mab infection.
繁缕组变种（SdLv），石竹科植物，是一种传统草药，用于治疗东亚地区的发热、盗汗和疟疾。炎症在多种细胞内病原体感染过程中对宿主防御和发病机制都起着至关重要的作用。在此，我们发现 SdLv 的草药提取物能有效减轻脓肿分枝杆菌（Mab）感染引起的炎症反应，但对刚地弓形虫（T. gondii）无效。在原代鼠巨噬细胞中，Mab 感染迅速激活核因子（NF）-κB 和丝裂原活化蛋白激酶（MAPK），并产生促炎细胞因子，如肿瘤坏死因子 α 和白细胞介素 6，而 SdLv 预处理则显著抑制了这些因子的产生。然而，柴胡（Bupleurum chinense DC.）或北柴胡（Bupleurum falcatum L.）的草药提取物则不影响 Mab 诱导的促炎反应。重要的是，我们证明了 Mab 感染巨噬细胞后，细胞内活性氧的产生迅速增加，这是 NF-κB 和 MAPK 信号通路激活的重要信号中间体，而 SdLv 预处理则能有效抑制其产生，但柴胡和北柴胡则不能。我们进一步发现，柴胡和北柴胡的处理，而不是 SdLv，会导致 NF-κB 和 MAPK 信号通路的激活和细胞内活性氧的产生。此外，SdLv 的口服给药可显著降低 Mab 感染小鼠的致死率。综上所述，这些结果表明 SdLv 可能可作为治疗 Mab 感染的有效方法。
