Carrimycin ameliorates lipopolysaccharide and cecal ligation and puncture-induced sepsis in mice

IF 4 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Junzhong LAI , Jiadi LIANG , Kunsen CHEN , Biyun GUAN , Zhirong CHEN , Linqin CHEN , Jiqiang FAN , Yong ZHANG , Qiumei LI , Jingqian SU , Qi CHEN , Jizhen LIN
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引用次数: 0

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.

卡利霉素可改善脂多糖和盲肠结扎及穿刺引起的小鼠败血症
卡瑞霉素(CA)于 2019 年被中国国家医药产品管理局(NMPA)批准用于治疗急性支气管炎和鼻窦炎,最近观察到它具有多方面的生物活性,包括抗炎、抗病毒和抗肿瘤特性。尽管有这些应用,但其在败血症治疗中的功效仍有待探索。本研究介绍了 CA 的一种新功能,证明它有能力减轻脂多糖(LPS)和盲肠结扎术(CLP)在小鼠模型中诱发的败血症。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,证实CA能显著降低LPS刺激下的促炎细胞因子水平,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)。此外,Western 印迹和免疫荧光分析表明,CA 能抑制 LPS 刺激的 RAW264.7 细胞中核因子卡巴 B(NF-κB)的活化。与这些发现相辅相成的是,体内实验表明,CA 能有效缓解 LPS 和 CLP 引发的 C57BL/6 小鼠器官炎症。通过 16S 测序获得的进一步研究结果表明,CA 在增强肠道微生物群多样性和调节代谢途径方面发挥着关键作用,特别是通过增加 CLP 小鼠体内短链脂肪酸的产生。值得注意的是,一项比较分析显示,CA 的抗炎功效超过了同等剂量的阿司匹林(ASP)和 TIENAM。总之,这些研究结果表明,CA 在治疗败血症方面具有显著的治疗潜力。这一发现为 CA 在败血症治疗中的临床应用提供了基础理论依据。
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来源期刊
Chinese Journal of Natural Medicines
Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY
CiteScore
7.50
自引率
4.30%
发文量
2235
期刊介绍: The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.
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