In the present study, 3-methylcarbazole and 1-methoxy-3-methylcarbazole were isolated from the culture of Streptomyces sp. LJK109, endophyte of Alpinia galanga Swartz. 3-methylcarbazole, a carbazole derivative, has be...In the present study, 3-methylcarbazole and 1-methoxy-3-methylcarbazole were isolated from the culture of Streptomyces sp. LJK109, endophyte of Alpinia galanga Swartz. 3-methylcarbazole, a carbazole derivative, has been found to be highly potent as anti-inflammatory agent. The immunomodulatory activity of these agents in toll like receptor (TLR)-activated RAW 264.7 macrophages induced by lipopolysaccharide (LPS), Poly(I:C), and pam3CSK was investigated by assessing nitric oxide (NO) and pro-inflammatory cytokines. The 3-methylcarbazoles dose-dependently suppressed the release of NO, PGE2, TNF-α, IL-1β, IL-6 and IL-10 in LPS- and pam3CSK-activated macrophages but not in Poly(I:C)-activated macrophages. Our results suggest that 3-methylcarbazoles can be further developed as a promising anti-inflammatory remedy.展开更多
Objective:To demonstrate the effect of dieckol from Eisenia bicyclis on osteoclastogenesis using RAW 264.7 cells.Methods:Murine macrophage RAW 264.7 cells were subjected to dieckol treatment,followed by treatment with...Objective:To demonstrate the effect of dieckol from Eisenia bicyclis on osteoclastogenesis using RAW 264.7 cells.Methods:Murine macrophage RAW 264.7 cells were subjected to dieckol treatment,followed by treatment with receptor activator of nuclear factor kappa-B ligand(RANKL)to induce osteoclastogenesis.Tartrate-resistant acid phosphatase(TRAP)activity was examined using a TRAP activity kit.Western blotting analysis was conducted to examine the level of osteoclast-related factors,including TRAP and calcitonin receptor(CTR),transcriptional factors,including c-Fos,c-Jun,and nuclear factor of activated T cells cytoplasmic 1(NFATc1),nuclear factor kappa-B(NF-κB),extracellular signal-regulated kinase(ERK),and c-Jun N-terminal kinase(JNK).Immunofluorescence staining was conducted to examine the expression of c-Fos,c-Jun,and NFATc1.Results:Among the four phlorotannin compounds present in Eisenia bicyclis,dieckol significantly hindered osteoclast differentiation and expression of RANKL-induced TRAP and CTR.In addition,dieckol downregulated the expression levels of c-Fos,c-Jun,NFATc1,ERK,and JNK,and suppressed NF-κB signaling.Conclusions:Dieckol can suppress RANKL-induced osteoclastogenesis.Therefore,it has therapeutic potential in treating osteoclastogenesis-associated diseases.展开更多
Geldanamycin (1) had been isolated as a major compound from Streptomyces zerumbet W14;an endophyte of Zingiber zerumbet (L.) Smith. Two new geldanamycin derivatives;17-(tryptamine)-17-demethoxygeldanamycin (2) and 17...Geldanamycin (1) had been isolated as a major compound from Streptomyces zerumbet W14;an endophyte of Zingiber zerumbet (L.) Smith. Two new geldanamycin derivatives;17-(tryptamine)-17-demethoxygeldanamycin (2) and 17-(5’-methoxytryptamine)-17-demethoxygeldanamycin (3) were synthe- sized and their anti-inflammatory activity was evaluated in LPS-induced macrophage RAW 264.7 cells by investigating their effects on the inhibition of production of NO, PGE2, TNF-α, IL-1β, IL-6 and IL-10. The data obtained were consistent with the modulation of TNF-α, IL-1β, IL-6, IL-10 production by these derivatives at concentration of 1 to 5 μg/ml. A similar effect was also observed when LPS-induced NO release and PGE2 production were tested. The inhibitory effects were shown in concentration-dependent manners. From the obtained results, it was concluded that two new gelda- namycin derivatives possess anti-inflammatory activity on LPS-induced RAW 264.7 cells. They could be useful for the management of inflammatory diseases.展开更多
We previously demonstrated that 2-hydroxypropyltrimethyl ammonium chloride chitosan(HACC)promoted the production of nitric oxide(NO)and proinflammatory cytokines by activating the mitogen-activated protein kinases(MAP...We previously demonstrated that 2-hydroxypropyltrimethyl ammonium chloride chitosan(HACC)promoted the production of nitric oxide(NO)and proinflammatory cytokines by activating the mitogen-activated protein kinases(MAPK)and Janus kinase(JAK)/STAT pathways in RAW 264.7 cells,indicating good immunomodulatory activity of HACC.In this study,to further investigate the immunomodulatory mechanisms of HACC,we determined the roles of phosphatidylinositol 3-kinase(PI3K)/Akt,activating protein(AP-1)and nuclear factor kappa B(NF-κB)in HACC-induced activation of RAW 264.7 cells by the western blotting.The results suggest that HACC promoted the phosphorylation of p85 and Akt.Furthermore,c-Jun and p65 were also increased after the treatment of RAW 264.7 cells with HACC,indicating the translocation of NF-κB and AP-1 from cytoplasm to nucleus.In addition,as scanning electron microscopy(SEM)analysis shows,the cell morphology changed after HACC treatment.These findings indicate that HACC activated MAPK,JAK/STAT,and PI3K/Akt signaling pathways dependent on AP-1 and NF-κB activation in RAW 264.7 cells,ultimately leading to the increase of NO and cytokines.展开更多
文摘In the present study, 3-methylcarbazole and 1-methoxy-3-methylcarbazole were isolated from the culture of Streptomyces sp. LJK109, endophyte of Alpinia galanga Swartz. 3-methylcarbazole, a carbazole derivative, has been found to be highly potent as anti-inflammatory agent. The immunomodulatory activity of these agents in toll like receptor (TLR)-activated RAW 264.7 macrophages induced by lipopolysaccharide (LPS), Poly(I:C), and pam3CSK was investigated by assessing nitric oxide (NO) and pro-inflammatory cytokines. The 3-methylcarbazoles dose-dependently suppressed the release of NO, PGE2, TNF-α, IL-1β, IL-6 and IL-10 in LPS- and pam3CSK-activated macrophages but not in Poly(I:C)-activated macrophages. Our results suggest that 3-methylcarbazoles can be further developed as a promising anti-inflammatory remedy.
基金supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSITNo. NRF-2020R1A2C1008527)
文摘Objective:To demonstrate the effect of dieckol from Eisenia bicyclis on osteoclastogenesis using RAW 264.7 cells.Methods:Murine macrophage RAW 264.7 cells were subjected to dieckol treatment,followed by treatment with receptor activator of nuclear factor kappa-B ligand(RANKL)to induce osteoclastogenesis.Tartrate-resistant acid phosphatase(TRAP)activity was examined using a TRAP activity kit.Western blotting analysis was conducted to examine the level of osteoclast-related factors,including TRAP and calcitonin receptor(CTR),transcriptional factors,including c-Fos,c-Jun,and nuclear factor of activated T cells cytoplasmic 1(NFATc1),nuclear factor kappa-B(NF-κB),extracellular signal-regulated kinase(ERK),and c-Jun N-terminal kinase(JNK).Immunofluorescence staining was conducted to examine the expression of c-Fos,c-Jun,and NFATc1.Results:Among the four phlorotannin compounds present in Eisenia bicyclis,dieckol significantly hindered osteoclast differentiation and expression of RANKL-induced TRAP and CTR.In addition,dieckol downregulated the expression levels of c-Fos,c-Jun,NFATc1,ERK,and JNK,and suppressed NF-κB signaling.Conclusions:Dieckol can suppress RANKL-induced osteoclastogenesis.Therefore,it has therapeutic potential in treating osteoclastogenesis-associated diseases.
文摘Geldanamycin (1) had been isolated as a major compound from Streptomyces zerumbet W14;an endophyte of Zingiber zerumbet (L.) Smith. Two new geldanamycin derivatives;17-(tryptamine)-17-demethoxygeldanamycin (2) and 17-(5’-methoxytryptamine)-17-demethoxygeldanamycin (3) were synthe- sized and their anti-inflammatory activity was evaluated in LPS-induced macrophage RAW 264.7 cells by investigating their effects on the inhibition of production of NO, PGE2, TNF-α, IL-1β, IL-6 and IL-10. The data obtained were consistent with the modulation of TNF-α, IL-1β, IL-6, IL-10 production by these derivatives at concentration of 1 to 5 μg/ml. A similar effect was also observed when LPS-induced NO release and PGE2 production were tested. The inhibitory effects were shown in concentration-dependent manners. From the obtained results, it was concluded that two new gelda- namycin derivatives possess anti-inflammatory activity on LPS-induced RAW 264.7 cells. They could be useful for the management of inflammatory diseases.
基金Supported by the National Key R&D Program of China(No.2018YFC0311305)the Key Research and Development Program of Shandong Province(Nos.2019GHY112015,2019YYSP028)。
文摘We previously demonstrated that 2-hydroxypropyltrimethyl ammonium chloride chitosan(HACC)promoted the production of nitric oxide(NO)and proinflammatory cytokines by activating the mitogen-activated protein kinases(MAPK)and Janus kinase(JAK)/STAT pathways in RAW 264.7 cells,indicating good immunomodulatory activity of HACC.In this study,to further investigate the immunomodulatory mechanisms of HACC,we determined the roles of phosphatidylinositol 3-kinase(PI3K)/Akt,activating protein(AP-1)and nuclear factor kappa B(NF-κB)in HACC-induced activation of RAW 264.7 cells by the western blotting.The results suggest that HACC promoted the phosphorylation of p85 and Akt.Furthermore,c-Jun and p65 were also increased after the treatment of RAW 264.7 cells with HACC,indicating the translocation of NF-κB and AP-1 from cytoplasm to nucleus.In addition,as scanning electron microscopy(SEM)analysis shows,the cell morphology changed after HACC treatment.These findings indicate that HACC activated MAPK,JAK/STAT,and PI3K/Akt signaling pathways dependent on AP-1 and NF-κB activation in RAW 264.7 cells,ultimately leading to the increase of NO and cytokines.
文摘为解析槲皮万寿菊素、槲皮素与叶黄素单独处理以及联合处理对急性肺损伤的作用机制,以脂多糖诱导构建RAW264.7细胞炎症模型,以一氧化氮(nitric oxide,NO)相对含量为评价指标,采用联合指数法确定槲皮万寿菊素与叶黄素以及槲皮素与叶黄素的最佳复配比例;分析比较槲皮万寿菊素、槲皮素与叶黄素单独及联合处理对RAW264.7细胞中炎症因子(肿瘤坏死因子-α、白细胞介素(interleukin,IL)-1β、IL-6)含量、丙二醛含量、超氧化物歧化酶活性以及谷胱甘肽过氧化物酶活性的影响;采用免疫印迹法测定核因子κB(nuclear factor kappa-B,NF-κB)信号通路中p65、p50以及沉默信息调节因子1(silent information regulator 1,SIRT1)、核因子E2相关因子2(nuclear factor-erythroid 2 related factor 2,Nrf2)和NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)的相对表达量。结果表明,槲皮万寿菊素与叶黄素高剂量3∶1(30μg/mL+10μg/mL)复配能够最大程度降低RAW264.7细胞中的NO相对含量。二者单独及联合作用均能通过降低炎症因子、丙二醛含量,提高超氧化物歧化酶和谷胱甘肽还原酶活性,下调NF-κB p65、p50以及NLRP3表达水平并上调SIRT1、Nrf2蛋白相对表达量发挥改善急性肺损伤的作用,且联合处理效果优于单独处理组。
