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Article

Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation

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Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
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Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Institute of Athletics, National Taiwan University of Sport, Taichung 40404, Taiwan
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Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan
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Department of Ophthalmology, Chi Mei Medical Center, Tainan 71004, Taiwan
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Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Graduate Institute of Biomedical Science, Research Center for Cancer Biology, China Medical University, Taichung 40403, Taiwan
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Division of Urology, Department of Surgery, Chi-Mei Medical Center, Tainan 71004, Taiwan
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Department of Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan
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Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editors: Concetta Saponaro, Raffaella Soleti, Simona De Summa and Antonia Cianciulli
Pharmaceuticals 2021, 14(6), 588; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060588
Received: 14 May 2021 / Revised: 10 June 2021 / Accepted: 15 June 2021 / Published: 18 June 2021
Piplartine (or Piperlongumine) is a natural alkaloid isolated from Piper longum 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 PGE2, 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. View Full-Text
Keywords: piplartine; macrophage; inflammation; NLRP3 inflammasome; sepsis piplartine; macrophage; inflammation; NLRP3 inflammasome; sepsis
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MDPI and ACS Style

Huang, C.-H.; Wang, S.-C.; Chen, I.-C.; Chen, Y.-T.; Liu, P.-L.; Fang, S.-H.; Huang, S.-P.; Yeh, H.-C.; Liu, C.-C.; Lee, P.-Y.; Lin, T.-C.; Cheng, W.-C.; Su, C.-C.; Wu, H.-E.; Chen, Y.-R.; Li, C.-Y. Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation. Pharmaceuticals 2021, 14, 588. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060588

AMA Style

Huang C-H, Wang S-C, Chen I-C, Chen Y-T, Liu P-L, Fang S-H, Huang S-P, Yeh H-C, Liu C-C, Lee P-Y, Lin T-C, Cheng W-C, Su C-C, Wu H-E, Chen Y-R, Li C-Y. Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation. Pharmaceuticals. 2021; 14(6):588. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060588

Chicago/Turabian Style

Huang, Chi-Han, 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, and Chia-Yang Li. 2021. "Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation" Pharmaceuticals 14, no. 6: 588. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060588

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