Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation
Piplartine (or Piperlongumine) is a natural alkaloid isolated from <i>Piper longum</i> L., which has been proposed to exhibit various biological properties such as anti-inflammatory effects; however, the effect of piplartine on sepsis has not been examined. This study was performed to ex...
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doaj-500dad005ef3493aaa1589b481938e8d2021-07-01T00:34:05ZengMDPI AGPharmaceuticals1424-82472021-06-011458858810.3390/ph14060588Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome ActivationChi-Han Huang0Shu-Chi Wang1I-Chen Chen2Yi-Ting Chen3Po-Len Liu4Shih-Hua Fang5Shu-Pin Huang6Hsin-Chih Yeh7Ching-Chih Liu8Po-Yen Lee9Tzu-Chieh Lin10Wei-Chung Cheng11Chia-Cheng Su12Hsin-En Wu13Yuan-Ru Chen14Chia-Yang Li15Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanInstitute of Athletics, National Taiwan University of Sport, Taichung 40404, TaiwanDepartment of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Biomedical Science, Research Center for Cancer Biology, China Medical University, Taichung 40403, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanPiplartine (or Piperlongumine) is a natural alkaloid isolated from <i>Piper longum</i> L., which has been proposed to exhibit various biological properties such as anti-inflammatory effects; however, the effect of piplartine on sepsis has not been examined. This study was performed to examine the anti-inflammatory activities of piplartine in vitro, ex vivo and in vivo using murine J774A.1 macrophage cell line, peritoneal macrophages, bone marrow-derived macrophages and an animal sepsis model. The results demonstrated that piplartine suppresses iNOS and COX-2 expression, reduces PGE<sub>2</sub>, TNF-α and IL-6 production, decreases the phosphorylation of MAPKs and NF-κB and attenuates NF-κB activity by LPS-activated macrophages. Piplartine also inhibits IL-1β production and suppresses NLRP3 inflammasome activation by LPS/ATP- and LPS/nigericin-activated macrophages. Moreover, piplartine reduces the production of nitric oxide (NO) and TNF-α, IL-6 and IL-1β, decreases LPS-induced tissue damage, attenuates infiltration of inflammatory cells and enhances the survival rate. Collectively, these results demonstrate piplartine exhibits anti-inflammatory activities in LPS-induced inflammation and sepsis and suggest that piplartine might have benefits for sepsis treatment.https://www.mdpi.com/1424-8247/14/6/588piplartinemacrophageinflammationNLRP3 inflammasomesepsis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chi-Han Huang Shu-Chi Wang I-Chen Chen Yi-Ting Chen Po-Len Liu Shih-Hua Fang Shu-Pin Huang Hsin-Chih Yeh Ching-Chih Liu Po-Yen Lee Tzu-Chieh Lin Wei-Chung Cheng Chia-Cheng Su Hsin-En Wu Yuan-Ru Chen Chia-Yang Li |
spellingShingle |
Chi-Han Huang Shu-Chi Wang I-Chen Chen Yi-Ting Chen Po-Len Liu Shih-Hua Fang Shu-Pin Huang Hsin-Chih Yeh Ching-Chih Liu Po-Yen Lee Tzu-Chieh Lin Wei-Chung Cheng Chia-Cheng Su Hsin-En Wu Yuan-Ru Chen Chia-Yang Li Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation Pharmaceuticals piplartine macrophage inflammation NLRP3 inflammasome sepsis |
author_facet |
Chi-Han Huang Shu-Chi Wang I-Chen Chen Yi-Ting Chen Po-Len Liu Shih-Hua Fang Shu-Pin Huang Hsin-Chih Yeh Ching-Chih Liu Po-Yen Lee Tzu-Chieh Lin Wei-Chung Cheng Chia-Cheng Su Hsin-En Wu Yuan-Ru Chen Chia-Yang Li |
author_sort |
Chi-Han Huang |
title |
Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation |
title_short |
Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation |
title_full |
Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation |
title_fullStr |
Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation |
title_full_unstemmed |
Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation |
title_sort |
protective effect of piplartine against lps-induced sepsis through attenuating the mapks/nf-κb signaling pathway and nlrp3 inflammasome activation |
publisher |
MDPI AG |
series |
Pharmaceuticals |
issn |
1424-8247 |
publishDate |
2021-06-01 |
description |
Piplartine (or Piperlongumine) is a natural alkaloid isolated from <i>Piper longum</i> L., which has been proposed to exhibit various biological properties such as anti-inflammatory effects; however, the effect of piplartine on sepsis has not been examined. This study was performed to examine the anti-inflammatory activities of piplartine in vitro, ex vivo and in vivo using murine J774A.1 macrophage cell line, peritoneal macrophages, bone marrow-derived macrophages and an animal sepsis model. The results demonstrated that piplartine suppresses iNOS and COX-2 expression, reduces PGE<sub>2</sub>, TNF-α and IL-6 production, decreases the phosphorylation of MAPKs and NF-κB and attenuates NF-κB activity by LPS-activated macrophages. Piplartine also inhibits IL-1β production and suppresses NLRP3 inflammasome activation by LPS/ATP- and LPS/nigericin-activated macrophages. Moreover, piplartine reduces the production of nitric oxide (NO) and TNF-α, IL-6 and IL-1β, decreases LPS-induced tissue damage, attenuates infiltration of inflammatory cells and enhances the survival rate. Collectively, these results demonstrate piplartine exhibits anti-inflammatory activities in LPS-induced inflammation and sepsis and suggest that piplartine might have benefits for sepsis treatment. |
topic |
piplartine macrophage inflammation NLRP3 inflammasome sepsis |
url |
https://www.mdpi.com/1424-8247/14/6/588 |
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