Abstract:Objective To investigate the anti-inflammatory effect of Cucurbitacin B on the inflammatory reaction of murine alveolar macrophages induced by lipopolysaccharide and its molecular mechanism. Methods The alveolar macrophages were randomly divided into five groups: blank group, LPS group, different concentrations of Cucurbitacin B (1μM, 2.5μM, 5μM)+) +LPS groups. All group cells were pretreated with different concentrations for 2 h, and followed by 1μg/mL LPS. The protein level of TNF-α,IL-1β,IL-6 and PGE2 were detected by ELISA assay, and the NO was detected by Griess methods, and its upstream protein i-NOS,COX-2, Nrf2 and HO-1 were detected by Western-blot. Results The secretion of TNF-α,IL-1β,IL-6 and PGE2 in LPS group were increased significantly than blank groups, while Cucurbitacin B suppressed its protein level inadose-dependent manner. The nuclear erythroid related factor 2 and antioxidant gene were activated while Cucurbitacin B was added into alveolar macrophages in adose-dependent manner. Conclusion Cucurbitacin B can inhibit the extracellar secretion of inflammatory cytokines production, and its molecular mechanism could be due to the promoting Nrf2 translocation to the nucleus, activating the expression of HO-1 gene, reducing the expression of iNOS and COX-2, and thereby alleviating the inflammatory reaction.
周康, 张永为, 陆新建, 马春芳. 葫芦素B对脂多糖诱导小鼠肺泡巨噬细胞炎症反应的影响[J]. 预防医学, 2017, 29(7): 680-683,688.
ZHOU Kang, ZHANG Yong-wei, LU Xin-jian, MA Chun-fang. A study on the effect of Cucurbitacin B on the inflammatory reaction of murine alveolar macrophages induced by lipopolysaccharide. Preventive Medicine, 2017, 29(7): 680-683,688.
[1] 张延亭,欧阳东云,何贤辉. 葫芦素B抗肿瘤作用及其机制研究进展[J]. 中国药理学与毒理学杂志,2012,26(1):112-115. [2] 张美侠,张洪亮,孙春艳,等. 葫芦素B在体内外对乳腺癌细胞的生长抑制作用[J]. 现代肿瘤医学,2009,17(1):16-19. [3] 刘亭彦,张美侠,邓意辉,等. 葫芦素B对喉癌细胞增殖和凋亡的影响及其机制研究[J]. 临床耳鼻咽喉头颈外科杂志,2008,22(9):403-407. [4] YANG T,LIU J,YANG M,et al. Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cells in vitro and in vivo by modulating multiple cellular pathways[J]. Oncotarget,2017,8(4):5800-5813. [5] DONG L,WANG S,CHEN M,et al. The activation of macrophage and upregulation of CD40 costimulatory molecule in lipopolysaccharide-induced acute lung injury[J]. J Biomed Biotechnol,2008(2008):852571. [6] DE PAOLI F,STAELS B,CHINETTI-GBAGUIDI G. Macrophage phenotypes and their modulation in atherosclerosis[J]. Circ J,2014,78(8):1775-1781. [7] KIM H R,KIM K W,JUNG H G,et al. Macrophage migration inhibitory factor enhances osteoclastogenesis through upregulation of RANKL expression from fibroblast-like synoviocytes in patients with rheumatoid arthritis[J]. Arthritis Res Ther,2011,13(2):R43. [8] NISHIHIRA J,MITSUYAMA K. Overview of the role of macrophage migration inhibitory factor (MIF) in inflammatory bowel disease[J]. Curr Pharm Des,2009,15(18):2104- 2109. [9] JEYASEELAN S,CHU H W,YOUNG S K,et al. Transcriptional profiling of lipopolysaccharide-induced acute lung injury[J]. Infect Immun,2004,72(12):7247-7256. [10] LAM D,HARRIS D,QIN Z. Inflammatory mediator profiling reveals immune properties of chemotactic gradients and macrophage mediator production inhibition during thioglycollate elicited peritoneal inflammation[J]. Mediators of Inflammation,2013(2013):1-9. [11] QIN X,QIU C,ZHAO L. Lysophosphatidylcholine perpetuates macrophage polarization toward classically activated phenotype in inflammation[J]. Cell Immunol,2014,289(1-2):185- 190. [12] BRUSCIA E M,BONFIELD T L. Cystic fibrosis lung immunity:the role of the macrophage[J]. J Innate Immun,2016,8(6):550-563. [13] LUCAS K,MAES M. Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation:possible treatments targeting the TLR4 pathway[J]. Mol Neurobiol,2013,48(1): 190-204. [14] GUO C,YANG L,WAN C X,et al. Anti-neuroinflammatory effect of Sophoraflavanone G from Sophora alopecuroides in LPS-activated BV2 microglia by MAPK,JAK/STAT and Nrf2/HO-1 signaling pathways[J]. Phytomedicine,2016,23(13): 1629-1637. [15] ZHU J,WANG H,CHEN F,et al. An overview of chemical inhibitors of the Nrf2-ARE signaling pathway and their potential applications in cancer therapy[J]. Free Radic Biol Med,2016(99): 544-556. [16] SEO K,YANG J H,KIM S C,et al. The antioxidant effects of isorhamnetin contribute to inhibit COX-2 expression in response to inflammation:a potential role of HO-1[J]. Inflammation,2014,37(3):712-722.