Abstract：
UNASSIGNED: Inulicin is a sesquiterpene lactone in Inulae Flos which is clinically used for the treatment of inflammatory diseases, such as cough, sputum production, and vomiting. This study aimed to demonstrate the anti-inflammatory activity and the underlying mechanism of inulicin by using lipopolysaccharide (LPS)-induced in vitro and in vivo models.
UNASSIGNED: LPS-stimulated RAW264.7 macrophages and mouse peritoneal macrophages (MPMs) were used for evaluating the in vitro anti-inflammatory activity of inulicin, while endotoxemia mice were used for evaluating its in vivo action. Cytokines\' levels were determined by ELISA. RT-qPCR and western blot were used for assaying the mRNA and protein levels of target genes. RAW264.7 macrophages transfected with reporter plasmid pNFκB-TA-luc or pAP1-TA-luc were used for assaying the activation of NF-κB or AP-1 signaling.
UNASSIGNED: Inulicin significantly inhibited LPS-induced production of NO, IL-6, c-c motif chemokine ligand 2 (CCL2), and IL-1β in both RAW264.7 cells and MPMs. Mechanism study indicated that it could suppress inducible nitric oxide synthase, IL-6, CCL2, and IL-1β mRNA levels in LPS-stimulated RAW264.7 cells. Moreover, inulicin inhibited IκBα phosphorylation and prevented the nuclear translocation of p65, thereby inactivating NF-κB signaling. Concurrently, it also inhibited AP-1 signaling by reducing the phosphorylation of C-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). In endotoxemia mice, a single intraperitoneal administration of inulicin could decrease the production of pro-inflammatory cytokines in serum and peritoneal lavage fluid.
UNASSIGNED: The present study demonstrates that inulicin possesses anti-inflammatory effects in vitro and in vivo, which suggests that inulicin might be a promising candidate for the treatment of inflammatory diseases.
UNASSIGNED: LPS-stimulated RAW264.7 macrophages and mouse peritoneal macrophages (MPMs) were used for evaluating the in vitro anti-inflammatory activity of inulicin, while endotoxemia mice were used for evaluating its in vivo action. Cytokines\' levels were determined by ELISA. RT-qPCR and western blot were used for assaying the mRNA and protein levels of target genes. RAW264.7 macrophages transfected with reporter plasmid pNFκB-TA-luc or pAP1-TA-luc were used for assaying the activation of NF-κB or AP-1 signaling.
UNASSIGNED: Inulicin significantly inhibited LPS-induced production of NO, IL-6, c-c motif chemokine ligand 2 (CCL2), and IL-1β in both RAW264.7 cells and MPMs. Mechanism study indicated that it could suppress inducible nitric oxide synthase, IL-6, CCL2, and IL-1β mRNA levels in LPS-stimulated RAW264.7 cells. Moreover, inulicin inhibited IκBα phosphorylation and prevented the nuclear translocation of p65, thereby inactivating NF-κB signaling. Concurrently, it also inhibited AP-1 signaling by reducing the phosphorylation of C-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). In endotoxemia mice, a single intraperitoneal administration of inulicin could decrease the production of pro-inflammatory cytokines in serum and peritoneal lavage fluid.
UNASSIGNED: The present study demonstrates that inulicin possesses anti-inflammatory effects in vitro and in vivo, which suggests that inulicin might be a promising candidate for the treatment of inflammatory diseases.
摘要：
■Inulicin是InulaeFlos中的倍半萜内酯，临床上用于治疗炎症性疾病，比如咳嗽,痰和呕吐。本研究旨在通过使用LPS诱导的体外和体内模型来证明inulicin的抗炎活性和潜在机制。
■使用LPS刺激的RAW264.7巨噬细胞和小鼠腹膜巨噬细胞（MPMs）来评估inulicin的体外抗炎活性，而内毒素血症小鼠用于评估其体内作用。通过ELISA测定细胞因子水平。RT-qPCR和蛋白质印迹用于测定靶基因的mRNA和蛋白质水平。用报道质粒pNFκB-TA-luc或pAP1-TA-luc转染的RAW264.7巨噬细胞用于测定NF-κB或AP-1信号传导的激活。
■菊粉显著抑制LPS诱导的NO产生,IL-6，c-c基序趋化因子配体2（CCL2）和IL-1β在RAW264.7细胞和MPM中。机制研究表明，它可以抑制诱导型一氧化氮合酶（iNOS），LPS刺激的RAW264.7细胞中IL-6、CCL2和IL-1βmRNA水平。此外，菊粉抑制IκBα磷酸化并阻止p65的核易位，从而使NF-κB信号失活。同时,它还通过减少JNK和ERK的磷酸化来抑制AP-1信号传导。在内毒素血症小鼠中，单次腹膜内施用伊米霉素可以减少血清和腹膜灌洗液中促炎细胞因子的产生。
■本研究表明，inulicin在体外和体内具有抗炎作用，这表明伊努霉素可能是治疗炎症性疾病的有希望的候选药物。
■使用LPS刺激的RAW264.7巨噬细胞和小鼠腹膜巨噬细胞（MPMs）来评估inulicin的体外抗炎活性，而内毒素血症小鼠用于评估其体内作用。通过ELISA测定细胞因子水平。RT-qPCR和蛋白质印迹用于测定靶基因的mRNA和蛋白质水平。用报道质粒pNFκB-TA-luc或pAP1-TA-luc转染的RAW264.7巨噬细胞用于测定NF-κB或AP-1信号传导的激活。
■菊粉显著抑制LPS诱导的NO产生,IL-6，c-c基序趋化因子配体2（CCL2）和IL-1β在RAW264.7细胞和MPM中。机制研究表明，它可以抑制诱导型一氧化氮合酶（iNOS），LPS刺激的RAW264.7细胞中IL-6、CCL2和IL-1βmRNA水平。此外，菊粉抑制IκBα磷酸化并阻止p65的核易位，从而使NF-κB信号失活。同时,它还通过减少JNK和ERK的磷酸化来抑制AP-1信号传导。在内毒素血症小鼠中，单次腹膜内施用伊米霉素可以减少血清和腹膜灌洗液中促炎细胞因子的产生。
■本研究表明，inulicin在体外和体内具有抗炎作用，这表明伊努霉素可能是治疗炎症性疾病的有希望的候选药物。
