白细胞介素-6 (IL-6) 是一种多效细胞因子，具有多种生物活性，包括炎症、造血、骨代谢、胚胎发育和其他基本过程。最近，IL-6被广泛认为是一种重要的促炎细胞因子，参与严重炎症性疾病（例如2019冠状病毒病（COVID-19））期间细胞因子风暴的发病机制。因此，IL-6被认为是抑制细胞因子风暴的治疗靶点。在本研究中，我们研究了刺五加的主要香豆素化合物异佛西丁对IL-6过表达的抑制作用及其分子机制。使用实时定量PCR测量IL-6 mRNA的表达，并使用蛋白质印迹法检测细胞内信号分子。当HuH-7人肝癌细胞系和HepG2人肝母细胞瘤细胞系用12-O-十四烷酰佛波醇13-乙酸酯(TPA)处理时，与HepG2相比，在HuH-7细胞中观察到IL-6 mRNA表达的显着诱导细胞。 Isofraxidin 以剂量依赖性方式显着抑制 HuH-7 细胞中 TPA 诱导的 IL-6 mRNA 表达。此外，isofraxidin 以剂量依赖性方式抑制 TPA 诱导的 ERK1/2 磷酸化。同样，MAPK/ERK 抑制剂 U0126 抑制 TPA 诱导的 IL-6 mRNA 表达。然而，异佛西丁对 TPA 诱导的 SAPK/JNK、Akt (Ser473) 和 STAT3 (Tyr705) 磷酸化、NF-κB p65 核转位和 IκB 降解没有影响。综上所述，异佛西丁通过选择性抑制 HuH-7 细胞中 MAPK/ERK 通路的激活来抑制 TPA 诱导的 IL-6 mRNA 过度表达，表明异佛西丁可能是治疗细胞因子风暴的有效抗炎剂。© 2024。作者获得 Springer-Verlag GmbH（德国施普林格自然公司的一部分）的独家许可。

Interleukin-6 (IL-6) is a pleiotropic cytokine that has many biological activities, including inflammation, hematopoiesis, bone metabolism, embryonic development, and other fundamental processes. Recently, IL-6 has been widely recognized as an important pro-inflammatory cytokine involved in cytokine storm pathogenesis during severe inflammatory diseases, such as coronavirus disease 2019 (COVID-19). Therefore, IL-6 is considered to be a therapeutic target for inhibiting cytokine storm. In the present study, we investigated the suppressive effect of isofraxidin, a major coumarin compound of Acanthopanax senticosus, on the overexpression of IL-6 and its molecular mechanism. The expression of IL-6 mRNA was measured using quantitative real-time PCR, and intracellular signaling molecules were detected using western blotting. When the HuH-7 human hepatocellular carcinoma cell line and HepG2 human hepatoblastoma cell line were treated with 12-O-tetradecanoylphorbol 13-acetate (TPA), a marked induction of IL-6 mRNA expression was observed in HuH-7 cells compared with HepG2 cells. Isofraxidin significantly suppressed TPA-induced IL-6 mRNA expression in HuH-7 cells in a dose-dependent manner. Furthermore, isofraxidin inhibited TPA-induced phosphorylation of ERK1/2 in a dose-dependent manner. Similarly, the MAPK/ERK inhibitor U0126 suppressed TPA-induced IL-6 mRNA expression. However, isofraxidin had no effects on TPA-induced phosphorylation of SAPK/JNK, Akt (Ser473), and STAT3 (Tyr705), nuclear translocation of NF-κB p65, and degradation of IκB. Taken together, isofraxidin suppresses TPA-induced overexpression of IL-6 mRNA by selectively inhibiting the activation of the MAPK/ERK pathway in HuH-7 cells, indicating that isofraxidin may be an effective anti-inflammatory agent for treating cytokine storm.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.