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

doi:10.3892/mmr.2019.10635

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

Authors:
- Ji‑Won Choi
- Sung‑Kon Lee
- Myoung‑Jin Kim
- Dong‑Gu Kim
- Joon‑Yeon Shin
- Ziqi Zhou
- Il‑Joo Jo
- Ho‑Joon Song
- Gi‑Sang Bae
- Sung‑Joo Park
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Affiliations: Department of Herbology, School of Korean Medicine, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea, Hanbang Cardio‑Renal Syndrome Research Center, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea, Division of Beauty Sciences, School of Natural Sciences, Wonkwang University, Iksan, Jeonbuk 54538, Republic of Korea
Published online on: September 2, 2019 https://doi.org/10.3892/mmr.2019.10635
Pages: 3709-3718
Copyright: © Choi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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