Zerumbone Suppresses the LPS-Induced Inflammatory Response and Represses Activation of the NLRP3 Inflammasome in Macrophages
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.652860/full |
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| author | Chia-Cheng Su Chia-Cheng Su Chia-Cheng Su Shu-Chi Wang I-Chen Chen I-Chen Chen I-Chen Chen Fang-Yen Chiu Po-Len Liu Chi-Han Huang Kuan-Hua Huang Shih-Hua Fang Wei-Chung Cheng Shu-Pin Huang Shu-Pin Huang Hsin-Chih Yeh Hsin-Chih Yeh Ching-Chih Liu Ching-Chih Liu Po-Yen Lee Po-Yen Lee Ming-Yii Huang Chia-Yang Li Chia-Yang Li Chia-Yang Li |
| author_facet | Chia-Cheng Su Chia-Cheng Su Chia-Cheng Su Shu-Chi Wang I-Chen Chen I-Chen Chen I-Chen Chen Fang-Yen Chiu Po-Len Liu Chi-Han Huang Kuan-Hua Huang Shih-Hua Fang Wei-Chung Cheng Shu-Pin Huang Shu-Pin Huang Hsin-Chih Yeh Hsin-Chih Yeh Ching-Chih Liu Ching-Chih Liu Po-Yen Lee Po-Yen Lee Ming-Yii Huang Chia-Yang Li Chia-Yang Li Chia-Yang Li |
| author_sort | Chia-Cheng Su |
| collection | DOAJ |
| description | 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-α, and IL-1β 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-κB 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, PGE2 and IL-6, suppressed the expression of iNOS and COX-2, repressed the phosphorylation of ERK, and decreased the activity of NF-κB in LPS-activated J774A.1 cells. In addition, zerumbone suppressed the production of IL-1β 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-κB 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. |
| first_indexed | 2024-12-21T11:04:41Z |
| format | Article |
| id | doaj.art-cf0b3bd126ba4225ab7e7adc9e40e005 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-21T11:04:41Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-cf0b3bd126ba4225ab7e7adc9e40e0052022-12-21T19:06:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-05-011210.3389/fphar.2021.652860652860Zerumbone Suppresses the LPS-Induced Inflammatory Response and Represses Activation of the NLRP3 Inflammasome in MacrophagesChia-Cheng Su0Chia-Cheng Su1Chia-Cheng Su2Shu-Chi Wang3I-Chen Chen4I-Chen Chen5I-Chen Chen6Fang-Yen Chiu7Po-Len Liu8Chi-Han Huang9Kuan-Hua Huang10Shih-Hua Fang11Wei-Chung Cheng12Shu-Pin Huang13Shu-Pin Huang14Hsin-Chih Yeh15Hsin-Chih Yeh16Ching-Chih Liu17Ching-Chih Liu18Po-Yen Lee19Po-Yen Lee20Ming-Yii Huang21Chia-Yang Li22Chia-Yang Li23Chia-Yang Li24Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanDivision of Urology, Department of Surgery, Chi-Mei Medical Center, Tainan, TaiwanDepartment of Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan, TaiwanDepartment of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanDepartment of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanDepartment of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanDivision of Urology, Department of Surgery, Chi-Mei Medical Center, Tainan, TaiwanInstitute of Athletics, National Taiwan University of Sport, Taichung, TaiwanGraduate Institute of Biomedical Science, Research Center for Cancer Biology, China Medical University, Taichung, Taiwan0Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan1Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan3Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan4Department of Ophthalmology, Chi Mei Medical Center, Taichung, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan5Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan6Department of Radiation Oncology, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan0Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan7Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanZerumbone 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-α, and IL-1β 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-κB 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, PGE2 and IL-6, suppressed the expression of iNOS and COX-2, repressed the phosphorylation of ERK, and decreased the activity of NF-κB in LPS-activated J774A.1 cells. In addition, zerumbone suppressed the production of IL-1β 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-κB 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.652860/fullzerumbonemacrophageinflammationNLRP3 inflammasomeMAPKs |
| spellingShingle | Chia-Cheng Su Chia-Cheng Su Chia-Cheng Su Shu-Chi Wang I-Chen Chen I-Chen Chen I-Chen Chen Fang-Yen Chiu Po-Len Liu Chi-Han Huang Kuan-Hua Huang Shih-Hua Fang Wei-Chung Cheng Shu-Pin Huang Shu-Pin Huang Hsin-Chih Yeh Hsin-Chih Yeh Ching-Chih Liu Ching-Chih Liu Po-Yen Lee Po-Yen Lee Ming-Yii Huang Chia-Yang Li Chia-Yang Li Chia-Yang Li Zerumbone Suppresses the LPS-Induced Inflammatory Response and Represses Activation of the NLRP3 Inflammasome in Macrophages Frontiers in Pharmacology zerumbone macrophage inflammation NLRP3 inflammasome MAPKs |
| title | Zerumbone Suppresses the LPS-Induced Inflammatory Response and Represses Activation of the NLRP3 Inflammasome in Macrophages |
| title_full | Zerumbone Suppresses the LPS-Induced Inflammatory Response and Represses Activation of the NLRP3 Inflammasome in Macrophages |
| title_fullStr | Zerumbone Suppresses the LPS-Induced Inflammatory Response and Represses Activation of the NLRP3 Inflammasome in Macrophages |
| title_full_unstemmed | Zerumbone Suppresses the LPS-Induced Inflammatory Response and Represses Activation of the NLRP3 Inflammasome in Macrophages |
| title_short | Zerumbone Suppresses the LPS-Induced Inflammatory Response and Represses Activation of the NLRP3 Inflammasome in Macrophages |
| title_sort | zerumbone suppresses the lps induced inflammatory response and represses activation of the nlrp3 inflammasome in macrophages |
| topic | zerumbone macrophage inflammation NLRP3 inflammasome MAPKs |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.652860/full |
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