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    標題: Zerumbone Suppresses the LPS-Induced Inflammatory Response and Represses Activation of the NLRP3 Inflammasome in Macrophages
    作者: Su, Chia-Cheng
    Wang, Shu-Chi
    Chen, I-Chen
    Chiu, Fang-Yen
    Liu, Po-Len
    Huang, Chi-Han
    Huang, Kuan-Hua
    Fang, Shih-Hua
    Cheng, Wei-Chung
    Huang, Shu-Pin
    Yeh, Hsin-Chih
    Liu, Ching-Chih
    Lee, Po-Yen
    Huang, Ming-Yii
    Li, Chia-Yang
    貢獻者: Kaohsiung Med Univ, Coll Med, Grad Inst Med
    Chi Mei Med Ctr, Div Urol, Dept Surg
    Chia Nan Univ Pharm & Sci, Dept Senior Citizen Serv Management
    Kaohsiung Med Univ, Dept Med Lab Sci & Biotechnol
    Kaohsiung Med Univ Hosp, Dept Pediat
    Kaohsiung Med Univ, Sch Med, Dept Pediat, Coll Med
    Kaohsiung Med Univ, Dept Resp Therapy, Coll Med
    Natl Taiwan Univ Sport, Inst Athlet
    China Med Univ, Grad Inst Biomed Sci, Res Ctr Canc Biol
    Kaohsiung Med Univ, Ctr Canc Res
    Kaohsiung Med Univ, Coll Med, Sch Med, Dept Urol
    Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Urol
    Kaohsiung Municipal Tatung Hosp, Dept Urol
    Chi Mei Med Ctr, Dept Ophthalmol, Taichung, Taiwan;[Lee, Po-Yen
    Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Ophthalmol
    Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Canc Ctr, Dept Radiat Oncol
    Kaohsiung Med Univ Hosp, Dept Med Res
    關鍵字: zerumbone
    macrophage
    inflammation
    NLRP3 inflammasome
    MAPKs
    日期: 2021
    上傳時間: 2023-11-11 11:51:57 (UTC+8)
    出版者: FRONTIERS MEDIA SA
    摘要: Zerumbone is a natural product isolated from the pinecone or shampoo ginger, Zingiber zerumbet (L.) Smith, which has a wide range of pharmacological activities, including anti-inflammatory effects. However, the effects of zerumbone on activation of the NLRP3 inflammasome in macrophages have not been examined. This study aimed to examine the effects of zerumbone on LPS-induced inflammatory responses and NLRP3 inflammasome activation using murine J774A.1 cells, murine peritoneal macrophages, and murine bone marrow-derived macrophages. Cells were treated with zerumbone following LPS or LPS/ATP treatment. Production of nitric oxide (NO) was measured by Griess reagent assay. The levels of IL-6, TNF-alpha, and IL-1 beta secretion were analyzed by ELISA. Western blotting analysis was performed to determine the expression of inducible NO synthase (iNOS), COX-2, MAPKs, and NLRP3 inflammasome-associated proteins. The activity of NF-kappa B was determined by a promoter reporter assay. The assembly of NLRP3 was examined by immunofluorescence staining and observed by confocal laser microscopy. Our experimental results indicated that zerumbone inhibited the production of NO, PGE(2) and IL-6, suppressed the expression of iNOS and COX-2, repressed the phosphorylation of ERK, and decreased the activity of NF-kappa B in LPS-activated J774A.1 cells. In addition, zerumbone suppressed the production of IL-1 beta and inhibited the activity of NLRP3 inflammasome in LPS/ATP- and LPS/nigericin-activated J774A.1 cells. On the other hand, we also found that zerumbone repressed the production of NO and proinflammatory cytokines in LPS-activated murine peritoneal macrophages and bone marrow-derived macrophages. In conclusion, our experimental results demonstrate that zerumbone effectively attenuates the LPS-induced inflammatory response in macrophages both in vitro and ex vivo by suppressing the activation of the ERK-MAPK and NF-kappa B signaling pathways as well as blocking the activation of the NLRP3 inflammasome. These results imply that zerumbone may be beneficial for treating sepsis and inflammasome-related diseases.
    關聯: FRONT PHARMACOL, v.12
    Appears in Collections:[高齡福祉養生管理系] 期刊論文

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