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Piperine ameliorates the severity of fibrosis via inhibition of TGF-β/SMAD signaling in a mouse model of chronic pancreatitis

Chronic pancreatitis (CP) is characterized by recurrent pancreatic injury, resulting in inflammation and fibrosis. Currently, there are no drugs for the treatment of pancreatic fibrosis associated with CP. Piperine, a natural alkaloid found in black pepper, has been reported to show anti-inflammator...

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Autores principales: Choi, Ji-Won, Lee, Sung-Kon, Kim, Myoung-Jin, Kim, Dong-Gu, Shin, Joon-Yeon, Zhou, Ziqi, Jo, Il-Joo, Song, Ho-Joon, Bae, Gi-Sang, Park, Sung-Joo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755249/
https://www.ncbi.nlm.nih.gov/pubmed/31485676
http://dx.doi.org/10.3892/mmr.2019.10635
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author Choi, Ji-Won
Lee, Sung-Kon
Kim, Myoung-Jin
Kim, Dong-Gu
Shin, Joon-Yeon
Zhou, Ziqi
Jo, Il-Joo
Song, Ho-Joon
Bae, Gi-Sang
Park, Sung-Joo
author_facet Choi, Ji-Won
Lee, Sung-Kon
Kim, Myoung-Jin
Kim, Dong-Gu
Shin, Joon-Yeon
Zhou, Ziqi
Jo, Il-Joo
Song, Ho-Joon
Bae, Gi-Sang
Park, Sung-Joo
author_sort Choi, Ji-Won
collection PubMed
description Chronic pancreatitis (CP) is characterized by recurrent pancreatic injury, resulting in inflammation and fibrosis. Currently, there are no drugs for the treatment of pancreatic fibrosis associated with CP. Piperine, a natural alkaloid found in black pepper, has been reported to show anti-inflammatory, anti-oxidative, and antitumor activities. Although piperine exhibits numerous properties in regards to the regulation of diverse diseases, the effects of piperine on CP have not been established. To investigate the effects of piperine on CP in vivo, we induced CP in mice through the repetitive administration of cerulein (50 µg/kg) six times at 1-h intervals, 5 times per week, for a total of 3 weeks. In the pre-treatment groups, piperine (1, 5, or 10 mg/kg) or corn oil were administrated orally at 1 h before the first cerulein injection, once a day, 5 times a week, for a total of 3 weeks. In the post-treatment groups, piperine (10 mg/kg) or corn oil was administered orally at 1 or 2 week after the first cerulein injection. Pancreases were collected for histological analysis. In addition, pancreatic stellate cells (PSCs) were isolated to examine the anti-fibrogenic effects and regulatory mechanisms of piperine. Piperine treatment significantly inhibited histological damage in the pancreas, increased the pancreatic acinar cell survival, reduced collagen deposition and reduced pro-inflammatory cytokines and chemokines. In addition, piperine treatment reduced the expression of fibrotic mediators, such as α-smooth muscle actin (α-SMA), collagen, and fibronectin 1 in the pancreas and PSCs. Moreover, piperine treatment reduced the production of transforming growth factor (TGF)-β in the pancreas and PSCs. Furthermore, piperine treatment inhibited TGF-β-induced pSMAD2/3 activation but not pSMAD1/5 in the PSCs. These findings suggest that piperine treatment ameliorates pancreatic fibrosis by inhibiting TGF-β/SMAD2/3 signaling during CP.
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spelling pubmed-67552492019-09-25 Piperine ameliorates the severity of fibrosis via inhibition of TGF-β/SMAD signaling in a mouse model of chronic pancreatitis Choi, Ji-Won Lee, Sung-Kon Kim, Myoung-Jin Kim, Dong-Gu Shin, Joon-Yeon Zhou, Ziqi Jo, Il-Joo Song, Ho-Joon Bae, Gi-Sang Park, Sung-Joo Mol Med Rep Articles Chronic pancreatitis (CP) is characterized by recurrent pancreatic injury, resulting in inflammation and fibrosis. Currently, there are no drugs for the treatment of pancreatic fibrosis associated with CP. Piperine, a natural alkaloid found in black pepper, has been reported to show anti-inflammatory, anti-oxidative, and antitumor activities. Although piperine exhibits numerous properties in regards to the regulation of diverse diseases, the effects of piperine on CP have not been established. To investigate the effects of piperine on CP in vivo, we induced CP in mice through the repetitive administration of cerulein (50 µg/kg) six times at 1-h intervals, 5 times per week, for a total of 3 weeks. In the pre-treatment groups, piperine (1, 5, or 10 mg/kg) or corn oil were administrated orally at 1 h before the first cerulein injection, once a day, 5 times a week, for a total of 3 weeks. In the post-treatment groups, piperine (10 mg/kg) or corn oil was administered orally at 1 or 2 week after the first cerulein injection. Pancreases were collected for histological analysis. In addition, pancreatic stellate cells (PSCs) were isolated to examine the anti-fibrogenic effects and regulatory mechanisms of piperine. Piperine treatment significantly inhibited histological damage in the pancreas, increased the pancreatic acinar cell survival, reduced collagen deposition and reduced pro-inflammatory cytokines and chemokines. In addition, piperine treatment reduced the expression of fibrotic mediators, such as α-smooth muscle actin (α-SMA), collagen, and fibronectin 1 in the pancreas and PSCs. Moreover, piperine treatment reduced the production of transforming growth factor (TGF)-β in the pancreas and PSCs. Furthermore, piperine treatment inhibited TGF-β-induced pSMAD2/3 activation but not pSMAD1/5 in the PSCs. These findings suggest that piperine treatment ameliorates pancreatic fibrosis by inhibiting TGF-β/SMAD2/3 signaling during CP. D.A. Spandidos 2019-10 2019-09-02 /pmc/articles/PMC6755249/ /pubmed/31485676 http://dx.doi.org/10.3892/mmr.2019.10635 Text en Copyright: © Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Choi, Ji-Won
Lee, Sung-Kon
Kim, Myoung-Jin
Kim, Dong-Gu
Shin, Joon-Yeon
Zhou, Ziqi
Jo, Il-Joo
Song, Ho-Joon
Bae, Gi-Sang
Park, Sung-Joo
Piperine ameliorates the severity of fibrosis via inhibition of TGF-β/SMAD signaling in a mouse model of chronic pancreatitis
title Piperine ameliorates the severity of fibrosis via inhibition of TGF-β/SMAD signaling in a mouse model of chronic pancreatitis
title_full Piperine ameliorates the severity of fibrosis via inhibition of TGF-β/SMAD signaling in a mouse model of chronic pancreatitis
title_fullStr Piperine ameliorates the severity of fibrosis via inhibition of TGF-β/SMAD signaling in a mouse model of chronic pancreatitis
title_full_unstemmed Piperine ameliorates the severity of fibrosis via inhibition of TGF-β/SMAD signaling in a mouse model of chronic pancreatitis
title_short Piperine ameliorates the severity of fibrosis via inhibition of TGF-β/SMAD signaling in a mouse model of chronic pancreatitis
title_sort piperine ameliorates the severity of fibrosis via inhibition of tgf-β/smad signaling in a mouse model of chronic pancreatitis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755249/
https://www.ncbi.nlm.nih.gov/pubmed/31485676
http://dx.doi.org/10.3892/mmr.2019.10635
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