Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 34141, Republic of Korea.
Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea.
Int J Mol Sci. 2024 Sep 19;25(18):10089. doi: 10.3390/ijms251810089.
Sepsis is an inflammatory condition causing organ failure due to an uncontrolled immune response to infection and remains a significant challenge. Crotonis Semen has displayed various pharmacological effects, yet its potential in protecting against sepsis and the mechanisms involved remains largely unclear. Here, we explored the antiseptic properties of Crotons Semen extract (CSE) in both LPS-stimulated J774 macrophages and mice subjected to sepsis through Cecal ligation and Puncture (CLP) or LPS induction. We found that CSE enhanced survival rates in mouse models with acute sepsis induced by CLP operation and LPS injection. Administering CSE also reduced levels of enzymes indicating organ damage, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK), in septic mice. Furthermore, CSE lowered the serum levels of inflammatory mediators and cytokines, such as NO, TNF-α, IL-1β, and IL-6, in septic mice. In LPS-stimulated J774 macrophages, CSE reduced the expression of pro-inflammatory proteins, including iNOS and COX-2. Moreover, CSE inhibited the phosphorylation of IκBα and IKK, key components of the NF-κB signaling pathway, thereby reducing inflammatory mediators and cytokines. These results demonstrate CSE's protective effects against sepsis through NF-κB pathway disruption, indicating its potential as a therapeutic option for acute inflammatory conditions.
脓毒症是一种炎症性疾病，由于对感染的失控免疫反应导致器官衰竭，仍然是一个重大挑战。巴豆具有多种药理作用，但它在预防脓毒症及其相关机制方面的潜力尚不清楚。在这里，我们通过脂多糖（LPS）刺激的 J774 巨噬细胞和盲肠结扎和穿刺（CLP）或 LPS 诱导的脓毒症小鼠模型，研究了巴豆种子提取物（CSE）的抗菌特性。我们发现，CSE 提高了 CLP 手术和 LPS 注射诱导的急性脓毒症小鼠模型的存活率。给予 CSE 还降低了脓毒症小鼠中表明器官损伤的酶的水平，如天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）和肌酸激酶（CK）。此外，CSE 降低了脓毒症小鼠血清中炎症介质和细胞因子的水平，如 NO、TNF-α、IL-1β 和 IL-6。在 LPS 刺激的 J774 巨噬细胞中，CSE 降低了促炎蛋白的表达，包括 iNOS 和 COX-2。此外，CSE 抑制了 IκBα 和 IKK 的磷酸化，IκBα 和 IKK 是 NF-κB 信号通路的关键组成部分，从而减少了炎症介质和细胞因子。这些结果表明 CSE 通过破坏 NF-κB 通路对脓毒症具有保护作用，表明其在急性炎症性疾病中的治疗潜力。
