Abstract:
Carrimycin (CA), sanctioned by China\'s National Medical Products Administration (NMPA) in 2019 for treating acute bronchitis and sinusitis, has recently been observed to exhibit multifaceted biological activities, encompassing anti-inflammatory, antiviral, and anti-tumor properties. Despite these applications, its efficacy in sepsis treatment remains unexplored. This study introduces a novel function of CA, demonstrating its capacity to mitigate sepsis induced by lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in mice models. Our research employed in vitro assays, real-time quantitative polymerase chain reaction (RT-qPCR), and RNA-seq analysis to establish that CA significantly reduces the levels of pro-inflammatory cytokines, namely tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6), in response to LPS stimulation. Additionally, Western blotting and immunofluorescence assays revealed that CA impedes Nuclear Factor Kappa B (NF-κB) activation in LPS-stimulated RAW264.7 cells. Complementing these findings, in vivo experiments demonstrated that CA effectively alleviates LPS- and CLP-triggered organ inflammation in C57BL/6 mice. Further insights were gained through 16S sequencing, highlighting CA\'s pivotal role in enhancing gut microbiota diversity and modulating metabolic pathways, particularly by augmenting the production of short-chain fatty acids in mice subjected to CLP. Notably, a comparative analysis revealed that CA\'s anti-inflammatory efficacy surpasses that of equivalent doses of aspirin (ASP) and TIENAM. Collectively, these findings suggest that CA exhibits significant therapeutic potential in sepsis treatment. This discovery provides a foundational theoretical basis for the clinical application of CA in sepsis management.
摘要:
卡里霉素(CA),2019年被中国国家药品监督管理局(NMPA)批准用于治疗急性支气管炎和鼻窦炎,最近观察到表现出多方面的生物活动,包括抗炎,抗病毒,和抗肿瘤特性。尽管有这些应用,其在脓毒症治疗中的疗效尚待探索.这项研究介绍了CA的一种新功能,证明其减轻小鼠模型中脂多糖(LPS)和盲肠结扎穿孔(CLP)诱导的脓毒症的能力。我们的研究采用了体外试验,实时定量聚合酶链反应(RT-qPCR),和RNA-seq分析,以确定CA显着降低促炎细胞因子的水平,即肿瘤坏死因子-α(TNF-α),白细胞介素1β(IL-1β),和白细胞介素6(IL-6),响应LPS刺激。此外,Western印迹和免疫荧光分析显示,CA阻碍了LPS刺激的RAW264.7细胞中核因子κB(NF-κB)的激活。补充这些发现,体内实验表明,CA可有效缓解C57BL/6小鼠中LPS和CLP触发的器官炎症。通过16S测序获得了进一步的见解,强调CA在增强肠道微生物多样性和调节代谢途径方面的关键作用,特别是通过增加接受CLP的小鼠中短链脂肪酸的产生。值得注意的是,一项比较分析显示,CA的抗炎功效超过了等效剂量的阿司匹林(ASP)和TIENAM。总的来说,这些发现提示CA在脓毒症治疗中具有显著的治疗潜力.这一发现为CA在脓毒症管理中的临床应用提供了基础理论基础。